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Sample records for apobec3 restriction factors

  1. Different mutagenic potential of HIV-1 restriction factors APOBEC3G and APOBEC3F is determined by distinct single-stranded DNA scanning mechanisms.

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    Anjuman Ara

    2014-03-01

    Full Text Available The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif (virus infectivity factor deficient HIV-1 virions to differing degrees by deaminating cytosines to uracils in single-stranded (-HIV-1 DNA. Upon replication of the (-DNA to (+DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils, thereby inducing C/G→T/A mutations that can functionally inactivate HIV-1. Although both APOBEC3F and APOBEC3G are expressed in cell types HIV-1 infects and are suppressed by Vif, there has been no prior biochemical analysis of APOBEC3F, in contrast to APOBEC3G. Using synthetic DNA substrates, we characterized APOBEC3F and found that similar to APOBEC3G; it is a processive enzyme and can deaminate at least two cytosines in a single enzyme-substrate encounter. However, APOBEC3F scanning movement is distinct from APOBEC3G, and relies on jumping rather than both jumping and sliding. APOBEC3F jumping movements were also different from APOBEC3G. The lack of sliding movement from APOBEC3F is due to an ¹⁹⁰NPM¹⁹² motif, since insertion of this motif into APOBEC3G decreases its sliding movements. The APOBEC3G NPM mutant induced significantly less mutations in comparison to wild-type APOBEC3G in an in vitro model HIV-1 replication assay and single-cycle infectivity assay, indicating that differences in DNA scanning were relevant to restriction of HIV-1. Conversely, mutation of the APOBEC3F ¹⁹¹Pro to ¹⁹¹Gly enables APOBEC3F sliding movements to occur. Although APOBEC3F ¹⁹⁰NGM¹⁹² could slide, the enzyme did not induce more mutagenesis than wild-type APOBEC3F, demonstrating that the unique jumping mechanism of APOBEC3F abrogates the influence of sliding on mutagenesis. Overall, we demonstrate key differences in the impact of APOBEC3F- and APOBEC3G-induced mutagenesis on HIV-1 that supports a model in which both the processive DNA scanning mechanism and preferred

  2. Tumultuous Relationship between the Human Immunodeficiency Virus Type 1 Viral Infectivity Factor (Vif) and the Human APOBEC-3G and APOBEC-3F Restriction Factors

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    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-01-01

    Summary: The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive c...

  3. HIV restriction by APOBEC3 in humanized mice.

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    John F Krisko

    2013-03-01

    Full Text Available Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3 family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV, Hepatitis B virus (HBV, Human Papilloma virus (HPV, and Human T Cell Leukemia virus (HTLV. The best characterized members of this family are APOBEC3G (A3G and APOBEC3F (A3F and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif. Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif.

  4. HIV-1 Vif versus the APOBEC3 cytidine deaminases: an intracellular duel between pathogen and host restriction factors.

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    Wissing, Silke; Galloway, Nicole L K; Greene, Warner C

    2010-10-01

    The Vif protein of HIV is essential for the effective propagation of this pathogenic retrovirus in vivo. Vif acts by preventing virion encapsidation of two potent antiviral factors, the APOBEC3G and APOBEC3F cytidine deaminases. Decreased encapsidation in part involves Vif-mediated recruitment of a ubiquitin E3 ligase complex that promotes polyubiquitylation and proteasome-mediated degradation of APOBEC3G/F. The resultant decline in intracellular levels of these enzymes leads to decreased encapsidation of APOBECG/F into budding virions. This review discusses recent advances in our understanding of the dynamic interplay of Vif with the antiviral APOBEC3 enzymes. PMID:20538015

  5. Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors.

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    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-06-01

    The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55(Gag), by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F. PMID:19487726

  6. Determinants of FIV and HIV Vif sensitivity of feline APOBEC3 restriction factors

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    Zhang, Zeli; Gu, Qinyong; Jaguva Vasudevan, Ananda Ayyappan; Hain, Anika; Kloke, Björn-Philipp; Hasheminasab, Sascha; Mulnaes, Daniel; Sato, Kei; Cichutek, Klaus; Häussinger, Dieter; Bravo, Ignacio G; Smits, Sander H. J.; Gohlke, Holger; Münk, Carsten

    2016-01-01

    Background Feline immunodeficiency virus (FIV) is a global pathogen of Felidae species and a model system for Human immunodeficiency virus (HIV)-induced AIDS. In felids such as the domestic cat (Felis catus), APOBEC3 (A3) genes encode for single-domain A3Z2s, A3Z3 and double-domain A3Z2Z3 anti-viral cytidine deaminases. The feline A3Z2Z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion ...

  7. Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution.

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    McLaughlin, Richard N; Gable, Jacob T; Wittkopp, Cristina J; Emerman, Michael; Malik, Harmit S

    2016-08-01

    LINE-1 (long interspersed element-1) retroelements are the only active autonomous endogenous retroelements in human genomes. Their retrotransposition activity has created close to 50% of the current human genome. Due to the apparent costs of this proliferation, host genomes have evolved multiple mechanisms to curb LINE-1 retrotransposition. Here, we investigate the evolution and function of the LINE-1 restriction factor APOBEC3A, a member of the APOBEC3 cytidine deaminase gene family. We find that APOBEC3A genes have evolved rapidly under diversifying selection in primates, suggesting changes in APOBEC3A have been recurrently selected in a host-pathogen "arms race." Nonetheless, in contrast to previous reports, we find that the LINE-1 restriction activity of APOBEC3A proteins has been strictly conserved throughout simian primate evolution in spite of its pervasive diversifying selection. Based on these results, we conclude that LINE-1s have not driven the rapid evolution of APOBEC3A in primates. In contrast to this conserved LINE-1 restriction, we find that a subset of primate APOBEC3A genes have enhanced antiviral restriction. We trace this gain of antiviral restriction in APOBEC3A to the common ancestor of a subset of Old World monkeys. Thus, APOBEC3A has not only maintained its LINE-1 restriction ability, but also evolved a gain of antiviral specificity against other pathogens. Our findings suggest that while APOBEC3A has evolved to restrict additional pathogens, only those adaptive amino acid changes that leave LINE-1 restriction unperturbed have been tolerated. PMID:27189538

  8. Atomic Force Microscopy Studies Provide Direct Evidence for Dimerization of the HIV Restriction Factor APOBEC3G*

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    Shlyakhtenko, Luda S.; Lushnikov, Alexander Y.; Li, Ming; Lackey, Lela; Harris, Reuben S.; Lyubchenko, Yuri L

    2010-01-01

    APOBEC3G (A3G) is an antiviral protein that binds RNA and single-stranded DNA (ssDNA). The oligomerization state of A3G is likely to be influenced by these nucleic acid interactions. We applied the power of nanoimaging atomic force microscopy technology to characterize the role of ssDNA in A3G oligomerization. We used recombinant human A3G prepared from HEK-293 cells and specially designed DNA substrates that enable free A3G to be distinguished unambiguously from DNA-bound protein complexes. ...

  9. Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.

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    David J Stanley

    2012-12-01

    Full Text Available Cellular restriction factors help to defend humans against human immunodeficiency virus (HIV. HIV accessory proteins hijack at least three different Cullin-RING ubiquitin ligases, which must be activated by the small ubiquitin-like protein NEDD8, in order to counteract host cellular restriction factors. We found that conjugation of NEDD8 to Cullin-5 by the NEDD8-conjugating enzyme UBE2F is required for HIV Vif-mediated degradation of the host restriction factor APOBEC3G (A3G. Pharmacological inhibition of the NEDD8 E1 by MLN4924 or knockdown of either UBE2F or its RING-protein binding partner RBX2 bypasses the effect of Vif, restoring the restriction of HIV by A3G. NMR mapping and mutational analyses define specificity determinants of the UBE2F NEDD8 cascade. These studies demonstrate that disrupting host NEDD8 cascades presents a novel antiretroviral therapeutic approach enhancing the ability of the immune system to combat HIV.

  10. Fv1 restriction and retrovirus vaccine immunity in Apobec3-deficient 129P2 mice.

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    Kalani Halemano

    Full Text Available Understanding the host genetics of the immune response in retrovirus infection models could provide insights for basic HIV vaccine discovery. In Friend retrovirus (FV infection of mice, Fv1 differentially inhibits N-tropic versus B-tropic FV infection by mediating a capsid-dependent post-entry block, Fv2 susceptibility governs splenomegaly induction, and Rfv3 resistance primes a stronger neutralizing antibody response due to more potent Apobec3 activity. Apobec3 polymorphisms in inbred mouse strains correlate with Rfv3 resistance and susceptibility, with one unresolved exception. The 129/OlaHsd (129P2 mouse strain is Fv2 and Rfv3 susceptible based on genotyping, but infection of 129P2 mice with B-tropic FV resulted in strong neutralizing antibody responses and no splenomegaly. Here we confirm that 129P2 mice are Fv1(nr/nr, explaining its resistance to B-tropic FV. Infection of 129P2 mice with NB-tropic FV, which can efficiently infect mice independent of Fv1 genotype, resulted in severe splenomegaly, high levels of viremia and weak neutralizing antibody responses regardless of Apobec3 status. Notably, high-dose B-tropic FV infection of 129P2 Apobec3-deficient mice induced significant adaptive immune responses and conferred high levels of protection following challenge with pathogenic NB-tropic FV. This immunological protection complemented previous studies that N-tropic FV can act as a live-attenuated vaccine in Fv1 (b/b mice. Altogether, the results obtained in 129P2 mice strengthen the conclusion that Rfv3 is encoded by Apobec3, and highlight Fv1 incompatibility as a retroviral vaccine paradigm in mice. Due to its susceptibility to disease that allows for pathogenic challenge studies, B-tropic FV infection of 129P2 mice may be a useful model to study the immunological pathways induced by retroviral capsid restriction.

  11. Definition of the interacting interfaces of Apobec3G and HIV-1 Vif using MAPPIT mutagenesis analysis.

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    Lavens, Delphine; Peelman, Frank; Van der Heyden, José; Uyttendaele, Isabel; Catteeuw, Dominiek; Verhee, Annick; Van Schoubroeck, Bertrand; Kurth, Julia; Hallenberger, Sabine; Clayton, Reginald; Tavernier, Jan

    2010-04-01

    The host restriction factor Apobec3G is a cytidine deaminase that incorporates into HIV-1 virions and interferes with viral replication. The HIV-1 accessory protein Vif subverts Apobec3G by targeting it for proteasomal degradation. We propose a model in which Apobec3G N-terminal domains symmetrically interact via a head-to-head interface containing residues 122 RLYYFW 127. To validate this model and to characterize the Apobec3G-Apobec3G and the Apobec3G-Vif interactions, the mammalian protein-protein interaction trap two-hybrid technique was used. Mutations in the head-to-head interface abrogate the Apobec3G-Apobec3G interaction. All mutations that inhibit Apobec3G-Apobec3G binding also inhibit the Apobec3G-Vif interaction, indicating that the head-to head interface plays an important role in the interaction with Vif. Only the D128K, P129A and T32Q mutations specifically affect the Apobec3G-Vif association. In our model, D128, P129 and T32 cluster at the edge of the head-to-head interface, possibly forming a Vif binding site composed of two Apobec3G molecules. We propose that Vif either binds at the Apobec3G head-to-head interface or associates with an RNA-stabilized Apobec3G oligomer. PMID:20015971

  12. A novel role for APOBEC3: Susceptibility to sexual transmission of murine acquired immunodeficiency virus (mAIDS is aggravated in APOBEC3 deficient mice

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    Jones Philip H

    2012-06-01

    Full Text Available Abstract Background APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV – the etiological agent of murine AIDs (mAIDs. Results We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner. Conclusion Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus.

  13. Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and human embryonic stem cells.

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    Wissing, Silke; Montano, Mauricio; Garcia-Perez, Jose Luis; Moran, John V; Greene, Warner C

    2011-10-21

    Members of the APOBEC3 (A3) family of cytidine deaminase enzymes act as host defense mechanisms limiting both infections by exogenous retroviruses and mobilization of endogenous retrotransposons. Previous studies revealed that the overexpression of some A3 proteins could restrict engineered human Long INterspersed Element-1 (LINE-1 or L1) retrotransposition in HeLa cells. However, whether endogenous A3 proteins play a role in restricting L1 retrotransposition remains largely unexplored. Here, we show that HeLa cells express endogenous A3B and A3C, whereas human embryonic stem cells (hESCs) express A3B, A3C, A3DE, A3F, and A3G. To study the relative contribution of endogenous A3 proteins in restricting L1 retrotransposition, we first generated small hairpin RNAs (shRNAs) to suppress endogenous A3 mRNA expression, and then assessed L1 mobility using a cell-based L1 retrotransposition assay. We demonstrate that in both HeLa and hESCs, shRNA-based knockdown of A3B promotes a ∼2-3.7-fold increase in the retrotransposition efficiency of an engineered human L1. Knockdown of the other A3s produced no significant increase in L1 activity. Thus, A3B appears to restrict engineered L1 retrotransposition in a broad range of cell types, including pluripotent cells.

  14. APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study.

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    Iraj Hosseini

    Full Text Available The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.

  15. Antiviral Warrior-APOBEC3G

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    WU Xiao-xia; MA Yi-cai

    2005-01-01

    This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs (acquired immure deficiency syndrome).The viral infectivity factor (Vif) induces rapid degradation of APOBEC3G by ubiquitination, which is a proteosome-dependent pathway. Precisely speaking, only in the virus-producing cell Vif expression is necessary; in its absence, infection of a subsequent target cell terminates at a postentry step through the action of the human APOBEC3G antiviral mechanism. Vif protein has two domains: one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ (Y/F) LA motif. Recently, the research on Vif has also revealed APOBEC3G is a novel component of innate immune system. In fact, APOBEC3G not only acts in DNA editing to block the replication of retroviruses such as HIV-1, but also is able to defend a wide spectrum of distantly related retroviruses and interferes with HBV through a different mechanism from HIV.

  16. APOBEC3G-UBA2 fusion as a potential strategy for stable expression of APOBEC3G and inhibition of HIV-1 replication

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    Li Lin

    2008-08-01

    Full Text Available Abstract Background Although APOBEC3G protein is a potent and innate anti-HIV-1 cellular factor, HIV-1 Vif counteracts the effect of APOBEC3G by promoting its degradation through proteasome-mediated proteolysis. Thus, any means that could prevent APOBEC3G degradation could potentially enhance its anti-viral effect. The UBA2 domain has been identified as an intrinsic stabilization signal that protects protein from proteasomal degradation. In this pilot study, we tested whether APOBEC3G, when it is fused with UBA2, can resist Vif-mediated proteasomal degradation and further inhibit HIV-1 infection. Results APOBEC3G-UBA2 fusion protein is indeed more resistant to Vif-mediated degradation than APOBEC3G. The ability of UBA2 domain to stabilize APOBEC3G was diminished when polyubiquitin was over-expressed and the APOBEC3G-UBA2 fusion protein was found to bind less polyubiquitin than APOBEC3G, suggesting that UBA2 stabilizes APOBEC3G by preventing ubiquitin chain elongation and proteasome-mediated proteolysis. Consistently, treatment of cells with a proteasome inhibitor MG132 alleviated protein degradation of APOBEC3G and APOBEC3G-UBA2 fusion proteins. Analysis of the effect of APOBEC3G-UBA2 fusion protein on viral infectivity indicated that infection of virus packaged from HEK293 cells expressing APOBEC3G-UBA2 fusion protein is significantly lower than those packaged from HEK293 cells over-producing APOBEC3G or APOBEC3G-UBA2 mutant fusion proteins. Conclusion Fusion of UBA2 to APOBEC3G can make it more difficult to be degraded by proteasome. Thus, UBA2 could potentially be used to antagonize Vif-mediated APOBEC3G degradation by preventing polyubiquitination. The stabilized APOBEC3G-UBA2 fusion protein gives stronger inhibitory effect on viral infectivity than APOBEC3G without UBA2.

  17. Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency

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    Bunupuradah Torsak

    2012-11-01

    Full Text Available Abstract Introduction Human APOBEC3G is a host defense factor that potently inhibits HIV replication. We hypothesize that HIV-infected children with a genetic variant of APOBEC3G will have a more rapid disease progression. Methods Antiretroviral therapy (ART-naïve children, aged 1–12 years old with CD4 15-24% and without severe HIV-related symptoms were enrolled. The children had CD4% and absolute CD4 counts every 12 weeks and HIV-RNA every 24 weeks until 144 weeks. ART was started when CD4% declined to APOBEC3G genetic variants were performed by PCR-based restriction fragment length polymorphism techniques from peripheral blood mononuclear cells. Random-effect linear regression analysis was performed to correlate APOBEC3G genotypes and disease progression. Results 147 children, 35% male, with a median (IQR age of 6.5 (4.3-8.8 years were enrolled. CDC N:A:B were 1:63:36%. Median baseline values were 20% for CD4% 605 cells/mm3 for CD4 count and 4.7 log10copies/mL for HIV-RNA. The frequencies of APOBEC3G genotypes AA (186H/H, AG (186H/R, GG (186R/R were 86%, 12%, and 2% respectively. The APOBEC3G genotype GG was associated with a significant decline in CD4% -5.1% (−8.9 to −1.2%, p3, pAPOBEC3G genotypes with HIV-RNA changes overtime (p=0.16 or progression to CDC B and C (p=0.49 were observed. Conclusions APOBEC3G genotype GG was significantly associated with a more rapid decline in CD4. APOBEC3G’s antiviral effects on HIV disease progression in children should be further explored.

  18. Noninfectious retrovirus particles drive the APOBEC3/Rfv3 dependent neutralizing antibody response.

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    Diana S Smith

    2011-10-01

    Full Text Available Members of the APOBEC3 family of deoxycytidine deaminases counteract a broad range of retroviruses in vitro through an indirect mechanism that requires virion incorporation and inhibition of reverse transcription and/or hypermutation of minus strand transcripts in the next target cell. The selective advantage to the host of this indirect restriction mechanism remains unclear, but valuable insights may be gained by studying APOBEC3 function in vivo. Apobec3 was previously shown to encode Rfv3, a classical resistance gene that controls the recovery of mice from pathogenic Friend retrovirus (FV infection by promoting a more potent neutralizing antibody (NAb response. The underlying mechanism does not involve a direct effect of Apobec3 on B cell function. Here we show that while Apobec3 decreased titers of infectious virus during acute FV infection, plasma viral RNA loads were maintained, indicating substantial release of noninfectious particles in vivo. The lack of plasma virion infectivity was associated with a significant post-entry block during early reverse transcription rather than G-to-A hypermutation. The Apobec3-dependent NAb response correlated with IgG binding titers against native, but not detergent-lysed virions. These findings indicate that innate Apobec3 restriction promotes NAb responses by maintaining high concentrations of virions with native B cell epitopes, but in the context of low virion infectivity. Finally, Apobec3 restriction was found to be saturable in vivo, since increasing FV inoculum doses resulted in decreased Apobec3 inhibition. By analogy, maximizing the release of noninfectious particles by modulating APOBEC3 expression may improve humoral immunity against pathogenic human retroviral infections.

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

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    Etienne, Lucie; Bibollet-Ruche, Frederic; Sudmant, Peter H.; Wu, Lily I.; Hahn, Beatrice H.; Emerman, Michael

    2015-01-01

    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. PMID:26394054

  20. 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.

  1. HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation

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    Mercenne, Gaëlle; Bernacchi, Serena; Richer, Delphine; Bec, Guillaume; Henriet, Simon; Paillart, Jean-Christophe; Marquet, Roland

    2009-01-01

    The HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells (including most natural HIV-1 targets) by counteracting the cellular cytosine deaminases APOBEC-3G (hA3G) and hA3F. The Vif-induced degradation of these restriction factors by the proteasome has been extensively studied, but little is known about the translational repression of hA3G and hA3F by Vif, which has also been proposed to participate in Vif function. Here, we studied Vif binding to hA3G mRNA ...

  2. Lack of association between intact/deletion polymorphisms of the APOBEC3B gene and HIV-1 risk.

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    Mayumi Imahashi

    Full Text Available OBJECTIVE: The human APOBEC3 family of proteins potently restricts HIV-1 replication APOBEC3B, one of the family genes, is frequently deleted in human populations. Two previous studies reached inconsistent conclusions regarding the effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo. METHODS: Intact (I and deletion (D polymorphisms of APOBEC3B were analyzed using PCR. The syphilis, HBV and HCV infection rates, as well as CD4(+ T cell counts and viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and D/D. HIV-1 replication kinetics was assayed in vitro using primary cells derived from PBMCs. RESULTS: A total of 248 HIV-1-infected Japanese men who have sex with men (MSM patients and 207 uninfected Japanese MSM were enrolled in this study. The genotype analysis revealed no significant differences between the APOBEC3B genotype ratios of the infected and the uninfected cohorts (p = 0.66. In addition, HIV-1 disease progression parameters were not associated with the APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited comparable HIV-1 susceptibility. CONCLUSION: Our analysis of a population-based matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a negligible role in eliminating HIV-1 in vivo.

  3. Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications

    Energy Technology Data Exchange (ETDEWEB)

    Holden, Lauren G.; Prochnow, Courtney; Chang, Y. Paul; Bransteitter, Ronda; Chelico, Linda; Sen, Udayaditya; Stevens, Raymond C.; Goodman, Myron F.; Chen, Xiaojiang S. (USC); (Scripps)

    2009-04-07

    The APOBEC family members are involved in diverse biological functions. APOBEC3G restricts the replication of human immunodeficiency virus (HIV), hepatitis B virus and retroelements by cytidine deamination on single-stranded DNA or by RNA binding. Here we report the high-resolution crystal structure of the carboxy-terminal deaminase domain of APOBEC3G (APOBEC3G-CD2) purified from Escherichia coli. The APOBEC3G-CD2 structure has a five-stranded {beta}-sheet core that is common to all known deaminase structures and closely resembles the structure of another APOBEC protein, APOBEC2. A comparison of APOBEC3G-CD2 with other deaminase structures shows a structural conservation of the active-site loops that are directly involved in substrate binding. In the X-ray structure, these APOBEC3G active-site loops form a continuous 'substrate groove' around the active centre. The orientation of this putative substrate groove differs markedly (by 90 degrees) from the groove predicted by the NMR structure. We have introduced mutations around the groove, and have identified residues involved in substrate specificity, single-stranded DNA binding and deaminase activity. These results provide a basis for understanding the underlying mechanisms of substrate specificity for the APOBEC family.

  4. Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

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    Krista A Delviks-Frankenberry

    2016-05-01

    Full Text Available Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV

  5. Minimal Contribution of APOBEC3-Induced G-to-A Hypermutation to HIV-1 Recombination and Genetic Variation.

    Science.gov (United States)

    Delviks-Frankenberry, Krista A; Nikolaitchik, Olga A; Burdick, Ryan C; Gorelick, Robert J; Keele, Brandon F; Hu, Wei-Shau; Pathak, Vinay K

    2016-05-01

    Although the predominant effect of host restriction APOBEC3 proteins on HIV-1 infection is to block viral replication, they might inadvertently increase retroviral genetic variation by inducing G-to-A hypermutation. Numerous studies have disagreed on the contribution of hypermutation to viral genetic diversity and evolution. Confounding factors contributing to the debate include the extent of lethal (stop codon) and sublethal hypermutation induced by different APOBEC3 proteins, the inability to distinguish between G-to-A mutations induced by APOBEC3 proteins and error-prone viral replication, the potential impact of hypermutation on the frequency of retroviral recombination, and the extent to which viral recombination occurs in vivo, which can reassort mutations in hypermutated genomes. Here, we determined the effects of hypermutation on the HIV-1 recombination rate and its contribution to genetic variation through recombination to generate progeny genomes containing portions of hypermutated genomes without lethal mutations. We found that hypermutation did not significantly affect the rate of recombination, and recombination between hypermutated and wild-type genomes only increased the viral mutation rate by 3.9 × 10-5 mutations/bp/replication cycle in heterozygous virions, which is similar to the HIV-1 mutation rate. Since copackaging of hypermutated and wild-type genomes occurs very rarely in vivo, recombination between hypermutated and wild-type genomes does not significantly contribute to the genetic variation of replicating HIV-1. We also analyzed previously reported hypermutated sequences from infected patients and determined that the frequency of sublethal mutagenesis for A3G and A3F is negligible (4 × 10-21 and1 × 10-11, respectively) and its contribution to viral mutations is far below mutations generated during error-prone reverse transcription. Taken together, we conclude that the contribution of APOBEC3-induced hypermutation to HIV-1 genetic

  6. APOBEC3G inhibits elongation of HIV-1 reverse transcripts.

    Directory of Open Access Journals (Sweden)

    Kate N Bishop

    2008-12-01

    Full Text Available APOBEC3G (A3G is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation.

  7. Human cellular restriction factors that target HIV-1 replication

    OpenAIRE

    Jeang Kuan-Teh; Luban Jeremy; Strebel Klaus

    2009-01-01

    Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5α), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of th...

  8. APOBEC3G oligomerization is associated with the inhibition of both Alu and LINE-1 retrotransposition.

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    Takayoshi Koyama

    Full Text Available Alu and LINE-1 (L1, which constitute ~11% and ~17% of the human genome, respectively, are transposable non-LTR retroelements. They transpose not only in germ cells but also in somatic cells, occasionally causing cancer. We have previously demonstrated that antiretroviral restriction factors, human APOBEC3 (hA3 proteins (A-H, differentially inhibit L1 retrotransposition. In this present study, we found that hA3 members also restrict Alu retrotransposition at differential levels that correlate with those observed previously for L1 inhibition. Through deletion analyses based on the best-characterized hA3 member human APOBEC3G (hA3G, its N-terminal 30 amino acids were required for its inhibitory activity against Alu retrotransposition. The inhibitory effect of hA3G on Alu retrotransposition was associated with its oligomerization that was affected by the deletion of its N-terminal 30 amino acids. Through structural modeling, the amino acids 24 to 28 of hA3G were predicted to be located at the interface of the dimer. The mutation of these residues resulted in abrogated hA3G oligomerization, and consistently abolished the inhibitory activity of hA3G against Alu retrotransposition. Importantly, the anti-L1 activity of hA3G was also associated with hA3G oligomerization. These results suggest that the inhibitory activities of hA3G against Alu and L1 retrotransposition might involve a common mechanism.

  9. Cell-specific Regulation of APOBEC3F by Interferons

    Institute of Scientific and Technical Information of China (English)

    Songcheng YING; Xuzhao ZHANG; Phuong Thi Nguyen SARKIS; Rongzhen XU; Xiaofang YU

    2007-01-01

    Human cytidine deaminase APOBEC3F (A3F) has broad anti-viral activity against hepatitis B virus and retroviruses including human immunodeficiency virus type 1. However, its regulation in viral natural target cells such CD4+ T lymphocytes, macrophages, and primary liver cells has not been well studied. Here we showed that A3F was up-regulated by interferon (IFN)-α in primary hepatocytes and multiple liver cell lines as well as macrophages. Although the IFN-α signaling pathway was active in T lymphoid cells and induction of other IFN stimulated genes such as PKR was detected, A3F and APOBEC3G (A3G) were not induced by IFN-o in these cells. Thus, additional factors other than known IFN-stimulated genes also regulated IFN-α-induced A3F expression distinctly. A3F and A3G expression levels in primary hepatocytes, especially after IFN-α stimulation, were comparable to those in CD4+ T lymphocytes in some individuals. Significant variations of A3F and A3G expression in primary hepatocytes from various subjects were observed. Individual variations in A3F and/or A3G regulation and expression might influence the clinical outcomes of hepatitis B infection.

  10. Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by HIV-1.

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    Luis Apolonia

    2015-01-01

    Full Text Available The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G (A3G and APOBEC3F (A3F, act as potent human immunodeficiency virus type-1 (HIV-1 restriction factors. These proteins require packaging into HIV-1 particles to exert their antiviral activities, but the molecular mechanism by which this occurs is incompletely understood. The nucleocapsid (NC region of HIV-1 Gag is required for efficient incorporation of A3G and A3F, and the interaction between A3G and NC has previously been shown to be RNA-dependent. Here, we address this issue in detail by first determining which RNAs are able to bind to A3G and A3F in HV-1 infected cells, as well as in cell-free virions, using the unbiased individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP method. We show that A3G and A3F bind many different types of RNA, including HIV-1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs. Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV-1 genomic RNA (gRNA and 7SL RNA are reduced, implying that these RNAs are not essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles formed with Gag lacking the NC domain (Gag ΔNC fail to encapsidate A3G/F. Here, we exploit this system by demonstrating that the addition of an assortment of heterologous RNA-binding proteins and domains to Gag ΔNC efficiently restored A3G/F packaging, indicating that A3G and A3F have the ability to engage multiple RNAs to ensure viral encapsidation. We propose that the rather indiscriminate RNA binding characteristics of A3G and A3F promote functionality by enabling recruitment into a wide range of retroviral particles whose packaged RNA genomes comprise divergent sequences.

  11. APOBEC3 Interference during Replication of Viral Genomes

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    Luc Willems

    2015-06-01

    Full Text Available Co-evolution of viruses and their hosts has reached a fragile and dynamic equilibrium that allows viral persistence, replication and transmission. In response, infected hosts have developed strategies of defense that counteract the deleterious effects of viral infections. In particular, single-strand DNA editing by Apolipoprotein B Editing Catalytic subunits proteins 3 (APOBEC3s is a well-conserved mechanism of mammalian innate immunity that mutates and inactivates viral genomes. In this review, we describe the mechanisms of APOBEC3 editing during viral replication, the viral strategies that prevent APOBEC3 activity and the consequences of APOBEC3 modulation on viral fitness and host genome integrity. Understanding the mechanisms involved reveals new prospects for therapeutic intervention.

  12. HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation.

    Science.gov (United States)

    Mercenne, Gaëlle; Bernacchi, Serena; Richer, Delphine; Bec, Guillaume; Henriet, Simon; Paillart, Jean-Christophe; Marquet, Roland

    2010-01-01

    The HIV-1 viral infectivity factor (Vif) allows productive infection of non-permissive cells (including most natural HIV-1 targets) by counteracting the cellular cytosine deaminases APOBEC-3G (hA3G) and hA3F. The Vif-induced degradation of these restriction factors by the proteasome has been extensively studied, but little is known about the translational repression of hA3G and hA3F by Vif, which has also been proposed to participate in Vif function. Here, we studied Vif binding to hA3G mRNA and its role in translational repression. Filter binding assays and fluorescence titration curves revealed that Vif tightly binds to hA3G mRNA. Vif overall binding affinity was higher for the 3'UTR than for the 5'UTR, even though this region contained at least one high affinity Vif binding site (apparent K(d) = 27 +/- 6 nM). Several Vif binding sites were identified in 5' and 3'UTRs using RNase footprinting. In vitro translation evidenced that Vif inhibited hA3G translation by two mechanisms: a main time-independent process requiring the 5'UTR and an additional time-dependent, UTR-independent process. Results using a Vif protein mutated in the multimerization domain suggested that the molecular mechanism of translational control is more complicated than a simple physical blockage of scanning ribosomes. PMID:19910370

  13. NF-IL6 (C/EBPβ) induces HIV-1 replication by inhibiting cytidine deaminase APOBEC3G

    OpenAIRE

    Shigemi M Kinoshita; Taguchi, Shizuka

    2008-01-01

    T cell activation is crucial for the productive HIV-1 infection of primary T cells; however, little is known about the host molecules involved in this process. We show that the host transcription factor NF-IL6 (also called C/EBPβ) renders primary CD4+ T cells highly permissive for HIV-1 replication. NF-IL6 facilitates reverse transcription of the virus by binding to and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at Ser-288 weakened its binding to APOBEC3G and s...

  14. Human APOBEC3G drives HIV-1 evolution and the development of drug resistance

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Tamoy [Los Alamos National Laboratory; Kim, Eun - Young [FEINBERG SCHOOL OF MEDS; Koning, Fransje [KING' S COLLEGE LONDON; Malim, Michael [KING' S COLLEGE LONDON; Wolinsky, Steven M [FEINBERG SCHOOL OF MEDS

    2008-01-01

    Human APOBEC3G (hA3G) is an innate virus restriction factor that induces deamination of specific cytidine residues in single-stranded human immunodeficiency virus type 1 (HIV-1) DNA. Whereas destructive hA3G editing leads to a profound loss of HIV-1 infectivity, more limited editing could be a source of adaptation and diversification. Here we show that the presence of hA3G in T-cells can drive the development of diversity in HIV-1 populations and that under selection pressure imposed by the nucleotide analog reverse transcriptase inhibitor 3TC ((-)2',3'-dideoxy-3'-thiacytidine), a single point mutation that confers 3TC resistance, methionine 184 to isoleucine (M1841), emerges rapidly and reaches fixation. These results provide strong evidence that mutation by hA3G is an important source of genetic variation on which natural selection acts to shape the structure of the viral population and drive the tempo of HIV-1 evolution.

  15. Elevated APOBEC3B Correlates with Poor Outcomes for Estrogen-Receptor-Positive Breast Cancers

    NARCIS (Netherlands)

    A.M. Sieuwerts (Anieta); S. Willis (Scooter); M.J. Burns (Michael); M.P. Look (Maxime); M.E.M.-V. Gelder (Marion E. Meijer-Van); A. Schlicker (Andreas); D.A.M. Heideman (Danielle); H. Jacobs (Heinz); L. Wessels (Lodewyk); B. Leyland-Jones (Brian); K.P. Gray (Kathryn); J.A. Foekens (John); R.S. Harris (Reuben); J.W.M. Martens (John)

    2014-01-01

    textabstractRecent observations connected DNA cytosine deaminase APOBEC3B to the genetic evolution of breast cancer. We addressed whether APOBEC3B is associated with breast cancer clinical outcomes. APOBEC3B messenger RNA (mRNA) levels were related in 1,491 primary breast cancers to disease-free (DF

  16. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhang, Xiao-Liang; Song, Jia-Hao; Pang, Wei; Zheng, Yong-Tang

    2016-07-18

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  17. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina)

    Science.gov (United States)

    ZHANG, Xiao-Liang; SONG, Jia-Hao; PANG, Wei; ZHENG, Yong-Tang

    2016-01-01

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  18. A whole genome screen for HIV restriction factors

    Directory of Open Access Journals (Sweden)

    Liu Li

    2011-11-01

    Full Text Available Abstract Background Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme, p21 and tetherin are well characterised. Results To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. Conclusions We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.

  19. APOBEC3G Impairs the Multimerization of the HIV-1 Vif Protein in Living Cells

    OpenAIRE

    Batisse, Julien; Guerrero, Santiago Xavier; Bernacchi, Serena; Richert, Ludovic; Godet, Julien; Goldschmidt, Valérie; Mély, Yves; Marquet, Roland; de Rocquigny, Hugues; Paillart, Jean-Christophe

    2013-01-01

    The HIV-1 viral infectivity factor (Vif) is a small basic protein essential for viral fitness and pathogenicity. Vif allows productive infection in nonpermissive cells, including most natural HIV-1 target cells, by counteracting the cellular cytosine deaminases APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G [A3G]) and A3F. Vif is also associated with the viral assembly complex and packaged into viral particles through interactions with the viral genomic RNA and t...

  20. Target cell APOBEC3C can induce limited G-to-A mutation in HIV-1.

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    Khaoula Bourara

    2007-10-01

    Full Text Available The evolutionary success of primate lentiviruses reflects their high capacity to mutate and adapt to new host species, immune responses within individual hosts, and, in recent years, antiviral drugs. APOBEC3G (A3G and APOBEC3F (A3F are host cell DNA-editing enzymes that induce extensive HIV-1 mutation that severely attenuates viral replication. The HIV-1 virion infectivity factor (Vif, expressed in vivo, counteracts the antiviral activity of A3G and A3F by inducing their degradation. Other APOBECs may contribute more to viral diversity by inducing less extensive mutations allowing viral replication to persist. Here we show that in APOBEC3C (A3C-expressing cells infected with the patient-derived HIV-1 molecular clones 210WW, 210WM, 210MW, and 210MM, and the lab-adapted molecular clone LAI, viral G-to-A mutations were detected in the presence of Vif expression. Mutations occurred primarily in the GA context and were relatively infrequent, thereby allowing for spreading infection. The mutations were absent in cells lacking A3C but were induced after transient expression of A3C in the infected target cell. Inhibiting endogenous A3C by RNA interference in Magi cells prevented the viral mutations. Thus, A3C is necessary and sufficient for G-to-A mutations in some HIV-1 strains. A3C-induced mutations occur at levels that allow replication to persist and may therefore contribute to viral diversity. Developing drugs that inhibit A3C may be a novel strategy for delaying viral escape from immune or antiretroviral inhibition.

  1. Target Cell APOBEC3C Can Induce Limited G-to-A Mutation in HIV-1

    Science.gov (United States)

    Bourara, Khaoula; Liegler, Teri J; Grant, Robert M

    2007-01-01

    The evolutionary success of primate lentiviruses reflects their high capacity to mutate and adapt to new host species, immune responses within individual hosts, and, in recent years, antiviral drugs. APOBEC3G (A3G) and APOBEC3F (A3F) are host cell DNA-editing enzymes that induce extensive HIV-1 mutation that severely attenuates viral replication. The HIV-1 virion infectivity factor (Vif), expressed in vivo, counteracts the antiviral activity of A3G and A3F by inducing their degradation. Other APOBECs may contribute more to viral diversity by inducing less extensive mutations allowing viral replication to persist. Here we show that in APOBEC3C (A3C)-expressing cells infected with the patient-derived HIV-1 molecular clones 210WW, 210WM, 210MW, and 210MM, and the lab-adapted molecular clone LAI, viral G-to-A mutations were detected in the presence of Vif expression. Mutations occurred primarily in the GA context and were relatively infrequent, thereby allowing for spreading infection. The mutations were absent in cells lacking A3C but were induced after transient expression of A3C in the infected target cell. Inhibiting endogenous A3C by RNA interference in Magi cells prevented the viral mutations. Thus, A3C is necessary and sufficient for G-to-A mutations in some HIV-1 strains. A3C-induced mutations occur at levels that allow replication to persist and may therefore contribute to viral diversity. Developing drugs that inhibit A3C may be a novel strategy for delaying viral escape from immune or antiretroviral inhibition. PMID:17967058

  2. Intracellular interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G multimerization is dependent on its association with RNA

    Directory of Open Access Journals (Sweden)

    Friew Yeshitila N

    2009-06-01

    Full Text Available Abstract Background Host restriction factor APOBEC3G (A3G blocks human immunodeficiency virus type 1 (HIV-1 replication by G-to-A hypermutation, and by inhibiting DNA synthesis and provirus formation. Previous reports have suggested that A3G is a dimer and its virion incorporation is mediated through interactions with viral or nonviral RNAs and/or HIV-1 Gag. We have now employed a bimolecular fluorescence complementation assay (BiFC to analyze the intracellular A3G-A3G, A3G-RNA, and A3G-Gag interactions in living cells by reconstitution of yellow fluorescent protein (YFP from its N- or C-terminal fragments. Results The results obtained with catalytic domain 1 and 2 (CD1 and CD2 mutants indicate that A3G-A3G and A3G-Gag multimerization is dependent on an intact CD1 domain, which is required for RNA binding. A mutant HIV-1 Gag that exhibits reduced RNA binding also failed to reconstitute BiFC with wild-type A3G, indicating a requirement for both HIV-1 Gag and A3G to bind to RNA for their multimerization. Addition of a non-specific RNA binding peptide (P22 to the N-terminus of a CD1 mutant of A3G restored BiFC and virion incorporation, but failed to inhibit viral replication, indicating that the mutations in CD1 resulted in additional defects that interfere with A3G's antiviral activity. Conclusion These studies establish a robust BiFC assay for analysis of intracellular interactions of A3G with other macromolecules. The results indicate that in vivo A3G is a monomer that forms multimers upon binding to RNA. In addition, we observed weak interactions between wild-type A3G molecules and RNA binding-defective mutants of A3G, which could explain previously described protein-protein interactions between purified A3G molecules.

  3. APOBEC3G levels predict rates of progression to AIDS

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    Wu Hulin

    2007-03-01

    Full Text Available Abstract Background APOBEC3G (hA3G is a newly discovered cellular factor of innate immunity that inhibits HIV replication in vitro. Whether hA3G conferrs protection against HIV in vivo is not known. To investigate the possible anti-HIV activity of hA3G in vivo, we examined hA3G mRNA abundance in primary human cells isolated from either HIV-infected or HIV-uninfected individuals, and found that hA3G mRNA levels follow a hierarchical order of long-term nonprogressors>HIV-uninfected>Progressors; and, hA3G mRNA abundance is correlated with surrogates of HIV disease progression: viral load and CD4 count. Another group later confirmed that HIV-infected subjects have lower hA3G mRNA levels than HIV-uninfected controls, but did not find correlations between hA3G mRNA levels and viral load or CD4 count. These conflicing results indicate that a more comprehensive, conclusive investigation of hA3G expression levels in various patient cohorts is urgently needed. Presentation of the hypothesis For exploring whether hA3G abundance might influence HIV disease progression, we have formulated a hypothesis that inlcudes two parts: a in vivo, the basal hA3G mRNA expression level per PBMC is a constant – with minor physiologic fluctuations – determined by host genetic and epigenetic elements in a healthy individual; and that the basal hA3G mRNA expression levels in a population follow a Normal (or Gaussian distribution; b that although HIV infects randomly, it results in more rapid disease progression in those with lower hA3G mRNA levels, and slower disease progression in those with higher hA3G mRNA levels. Testing the hypothesis This hypothesis could be tested by a straighforward set of experiments to compare the distribution of hA3G mRNA levels in HIV-uninfected healthy individuals and that in HIV-infected, antiretroviral therapy-naïve subjects who are at early and late stages of infection. Implication of the hypothesis Testing this hypothesis will have

  4. Rationalisation of the differences between APOBEC3G structures from crystallography and NMR studies by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Flavia Autore

    Full Text Available The human APOBEC3G (A3G protein is a cellular polynucleotide cytidine deaminase that acts as a host restriction factor of retroviruses, including HIV-1 and various transposable elements. Recently, three NMR and two crystal structures of the catalytic deaminase domain of A3G have been reported, but these are in disagreement over the conformation of a terminal beta-strand, beta2, as well as the identification of a putative DNA binding site. We here report molecular dynamics simulations with all of the solved A3G catalytic domain structures, taking into account solubility enhancing mutations that were introduced during derivation of three out of the five structures. In the course of these simulations, we observed a general trend towards increased definition of the beta2 strand for those structures that have a distorted starting conformation of beta2. Solvent density maps around the protein as calculated from MD simulations indicated that this distortion is dependent on preferential hydration of residues within the beta2 strand. We also demonstrate that the identification of a pre-defined DNA binding site is prevented by the inherent flexibility of loops that determine access to the deaminase catalytic core. We discuss the implications of our analyses for the as yet unresolved structure of the full-length A3G protein and its biological functions with regard to hypermutation of DNA.

  5. Research progress of association between the polymorphisms of APOBEC3 G, PSIP1, SAMHD1 gene and HIV-1/AIDS%APOBEC3 G、PSIP1和AMHD1基因多态性与HIV-1/AIDS关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    李秋炎; 乔远东; 张学龙; 徐丽丹

    2015-01-01

    The host genetic background is one of the major factors causing different phenotype between individuals after HIV-1 infection.Many studies found thatAPOBEC3 G, LEDGF/p75, and SAMHD1 play an important role in HIV-1 replication cycle.APOBEC3G has a broad antiviral activity,LEDGF/p75 can tether HIV-1 to the chromosome through interacting with integrase, and SAMHD1 can inhibit HIV-1 replication by its dNTPase and RNase activities.In this review, we summarize the research progress in the polymorphisms of APOBEC3 G, PSIP1 and SAMHD1 genes that encode the aforementioned proteins, their susceptibility to HIV-1 infection and association with AIDS.%宿主遗传背景是导致人类免疫缺陷病毒(HIV)感染后不同个体间表型差异的主要因素之一.许多研究表明,APOBEC3 G、LEDGF/p75和SAMHD1在HIV-1复制周期中起到重要作用.其中,APOBEC3G具有广谱的抗逆转录病毒活性,可以有效的抑制HIV-1的复制;LEDGF/p75可以与整合酶结合,促进HIV-1整合到宿主基因组中;SAMHD1具有脱氧核苷三磷酸酶(dNTP ase)活性和核酸外切酶(RNase)活性,起到抑制病毒复制的作用.本文将对上述蛋白编码基因APOBEC3 G、PSIP1和SAMHD1基因多态性与HIV-1易感性和AIDS的相关性进展作一综述.

  6. Multi-scale modeling of HIV infection in vitro and APOBEC3G-based anti-retroviral therapy.

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    Iraj Hosseini

    2012-02-01

    Full Text Available The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell, cellular and extracellular (multicellular events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions, whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis.

  7. Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers.

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    Sieuwerts, Anieta M; Willis, Scooter; Burns, Michael B; Look, Maxime P; Meijer-Van Gelder, Marion E; Schlicker, Andreas; Heideman, Marinus R; Jacobs, Heinz; Wessels, Lodewyk; Leyland-Jones, Brian; Gray, Kathryn P; Foekens, John A; Harris, Reuben S; Martens, John W M

    2014-12-01

    Recent observations connected DNA cytosine deaminase APOBEC3B to the genetic evolution of breast cancer. We addressed whether APOBEC3B is associated with breast cancer clinical outcomes. APOBEC3B messenger RNA (mRNA) levels were related in 1,491 primary breast cancers to disease-free (DFS), metastasis-free (MFS), and overall survival (OS). For independent validation, APOBEC3B mRNA expression was associated with patient outcome data in five additional cohorts (over 3,500 breast cancer cases). In univariate Cox regression analysis, increasing APOBEC3B expression as a continuous variable was associated with worse DFS, MFS, and OS (hazard ratio [HR] = 1.20, 1.21, and 1.24, respectively; all P DFS (continuous variable: HR = 1.29, P = .001; dichotomized at the median level, HR = 1.66, P = .0002). This implies that APOBEC3B is a marker of pure prognosis in ER + disease. These findings were confirmed in the analyses of five independent patient sets. In these analyses, APOBEC3B expression dichotomized at the median level was associated with adverse outcomes (METABRIC discovery and validation, 788 and 706 ER + cases, disease-specific survival (DSS), HR = 1.77 and HR = 1.77, respectively, both P DFS, HR = 1.57, P = 2.46E-04; NKI295, 181 ER + cases, DFS, HR = 1.72, P = .054; and BIG 1-98, 1,219 ER + cases, breast-cancer-free interval (BCFI), HR = 1.42, P = 0.0079). APOBEC3B is a marker of pure prognosis and poor outcomes for ER + breast cancer, which strongly suggests that genetic aberrations induced by APOBEC3B contribute to breast cancer progression.

  8. APOBEC3G targets human T-cell leukemia virus type 1

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    Imada Kazunori

    2005-05-01

    Full Text Available Abstract Background Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G is a host cellular protein with a broad antiviral activity. It inhibits infectivitiy of a wide variety of retroviruses by deaminating deoxycytidine (dC into deoxyuridine (dU in newly synthesized minus strand DNA, resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the mechanism of its function, we have examined the antiviral activity of APOBEC3G on human T-cell leukemia virus type 1 (HTLV-1, the first identified human retrovirus. Results In this study, we have demonstrated that overexpressed as well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive mutants of APOBEC3G also inhibited HTLV-1 and no G-to-A hypermutation was induced by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human immunodeficiency virus type 1 (HIV-1 vif gene into HTLV-1 producing cell line, MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion incorporation, which resulted in upregulation of the infectivity of produced viruses. Conclusion APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 without exerting its cytidine deaminase activity. These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission.

  9. Requirement for Fc Effector Mechanisms in the APOBEC3/Rfv3-Dependent Neutralizing Antibody Response

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    Halemano, Kalani; Barrett, Bradley S.; Heilman, Karl J.; Morrison, Thomas E.

    2015-01-01

    Antiretroviral neutralizing antibody (NAb) responses are often evaluated in the absence of Fc-dependent immune effectors. In murine Friend retrovirus infection, Apobec3/Rfv3 promotes a potent polyclonal NAb response. Here, we show that the Apobec3/Rfv3-dependent NAb response correlated with virus-specific IgG2 titers and that the in vivo neutralization potency of Apobec3/Rfv3-resistant antisera was dependent on activating Fcγ receptors but not complement. The data strengthen retroviral vaccine strategies aimed at eliciting NAbs that activate specific Fcγ receptors. PMID:25589647

  10. APOBEC3G-depleted resting CD4+ T cells remain refractory to HIV1 infection.

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    Francesca R Santoni de Sio

    Full Text Available BACKGROUND: CD4+ T lymphocytes are the primary targets of HIV1 but cannot be infected when fully quiescent, due to a post-entry block preventing the completion of reverse transcription. Chiu et al. recently proposed that this restriction reflects the action of APOBEC3G (A3G. They further suggested that T cell activation abrogates the A3G-mediated block by directing this protein to a high molecular mass complex. METHODOLOGY/PRINCIPAL FINDINGS: In the present work, we sought to explore further this model. However, we found that effective suppression of A3G by combined RNA interference and expression of HIV1 Vif does not relieve the restrictive phenotype of post-activation resting T cells. We also failed to find a correlation between HIV resistance and the presence of A3G in a low molecular complex in primary T cells. CONCLUSIONS/SIGNIFICANCE: We conclude that A3G is unlikely to play a role in the HIV restrictive phenotype of quiescent T lymphocytes.

  11. APOBEC3G has the ability to programme T cell plasticity.

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    Garg, Anuradha; Kaul, Deepak

    2016-07-01

    Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology has assumed importance because of its role in oncogenesis. In this context, the present study was addressed to understand the immune-modulatory role of APOBEC3G through its effect upon the T-cell plasticity phenomenon. Such an attempt revealed that APOBEC3G has the inherent capacity to regulate genes coding for STAT3, NF-κB, CCL5, IL-6, IL-4, IFN-γ, IL-10 and IL-17 coupled with downregulation of Treg cells within human peripheral blood mononuclear cells (PBMCs) without any noticeable influence upon CD4(+) and CD8(+) cell number. On the basis of these findings, we propose that APOBEC3G has the ability to induce T cell plasticity and modulate immune response. PMID:27282578

  12. Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment

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    Monajemi Mahdis

    2012-04-01

    Full Text Available Abstract The enzyme APOBEC3G (A3G mutates the human immunodeficiency virus (HIV genome by converting deoxycytidine (dC to deoxyuridine (dU on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G’s standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.

  13. APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and Influencing LINE Reverse Transcriptase Activity

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    Liang, Weizi; Xu, Jiwei; Yuan, Wensu; Song, Xuan; Zhang, Jianyong; Wei, Wei; Yu, Xiao-Fang; Yang, Ying

    2016-01-01

    Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrotransposition are not all well characterized; here, we confirm that both A3B and A3DE have a strong ability to inhibit LINE-1 retrotransposition. A3DE interacts with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner. Moreover, A3DE binds to LINE-1 RNA and ORF1 protein in cell culture system. Fluorescence microscopy demonstrated that A3DE co-localizes with ORF1p in cytoplasm. Furthermore, A3DE inhibits LINE-1 reverse transcriptase activity in LINE-1 ribonucleoprotein particles in a cytidine deaminase-independent manner. In contrast, A3B has less inhibitory effects on LINE-1 reverse transcriptase activity despite its strong inhibition of LINE-1 retrotransposition. This study demonstrates that different A3 proteins have been evolved to inhibit LINE-1 activity through distinct mechanisms. PMID:27428332

  14. Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating APOBEC3G and APOBEC3F.

    Science.gov (United States)

    Khatua, Atanu K; Taylor, Harry E; Hildreth, James E K; Popik, Waldemar

    2010-04-25

    Human cytidine deaminases, including APOBEC3G (A3G) and A3F, are part of a cellular defense system against retroviruses and retroelements including non-LTR retrotransposons LINE-1 (L1) and Alu. Expression of cellular A3 proteins is sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3 proteins transferred in exosomes on retroelement mobilization is unknown. Here, we demonstrate for the first time that exosomes secreted by CD4(+)H9 T cells and mature monocyte-derived dendritic cells encapsidate A3G and A3F and inhibit L1 and Alu retrotransposition. A3G is the major contributor to the inhibitory activity of exosomes, however, the contribution of A3F in H9 exosomes cannot be excluded. Additionally, we show that exosomes encapsidate mRNAs coding for A3 proteins. A3G mRNA, and less so A3F, was enriched in exosomes secreted by H9 cells. Exosomal A3G mRNA was functional in vitro. Whether exosomes inhibit retrotransposons in vivo requires further investigation.

  15. The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer

    Science.gov (United States)

    Law, Emily K.; Sieuwerts, Anieta M.; LaPara, Kelly; Leonard, Brandon; Starrett, Gabriel J.; Molan, Amy M.; Temiz, Nuri A.; Vogel, Rachel Isaksson; Meijer-van Gelder, Marion E.; Sweep, Fred C. G. J.; Span, Paul N.; Foekens, John A.; Martens, John W. M.; Yee, Douglas; Harris, Reuben S.

    2016-01-01

    Breast tumors often display extreme genetic heterogeneity characterized by hundreds of gross chromosomal aberrations and tens of thousands of somatic mutations. Tumor evolution is thought to be ongoing and driven by multiple mutagenic processes. A major outstanding question is whether primary tumors have preexisting mutations for therapy resistance or whether additional DNA damage and mutagenesis are necessary. Drug resistance is a key measure of tumor evolvability. If a resistance mutation preexists at the time of primary tumor presentation, then the intended therapy is likely to fail. However, if resistance does not preexist, then ongoing mutational processes still have the potential to undermine therapeutic efficacy. The antiviral enzyme APOBEC3B (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B) preferentially deaminates DNA C-to-U, which results in signature C-to-T and C-to-G mutations commonly observed in breast tumors. We use clinical data and xenograft experiments to ask whether APOBEC3B contributes to ongoing breast tumor evolution and resistance to the selective estrogen receptor modulator, tamoxifen. First, APOBEC3B levels in primary estrogen receptor–positive (ER+) breast tumors inversely correlate with the clinical benefit of tamoxifen in the treatment of metastatic ER+ disease. Second, APOBEC3B depletion in an ER+ breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. Third, APOBEC3B overexpression accelerates the development of tamoxifen resistance in murine xenograft experiments by a mechanism that requires the enzyme’s catalytic activity. These studies combine to indicate that APOBEC3B promotes drug resistance in breast cancer and that inhibiting APOBEC3B-dependent tumor evolvability may be an effective strategy to improve efficacies of targeted cancer therapies. PMID:27730215

  16. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity

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    Joshua R. Kane

    2015-05-01

    Full Text Available HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac] and non-primate (FIV, BIV, and MVV viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA, for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity.

  17. Inhibition of hepatitis B virus replication by APOBEC3G in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Yan-Chang Lei; Dong-Liang Yang; You-Hua Hao; Zheng-Mao Zhang; Yong-Jun Tian; Bao-Ju Wang; Yan Yang; Xi-Ping Zhao; Meng-Ji Lu; Fei-Li Gong

    2006-01-01

    AIM: To investigate the effect of APOBEC3G mediated antiviral activity against hepatitis B virus (HBV) in cell cultures and replication competent HBV vector-based mouse model.METHODS: The mammalian hepatoma cells Huh7 and HepG2 were cotransfected with various amounts of CMV-driven expression vector encoding APOBEC3G and replication competent 1.3 fold over-length HBV. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA. The expression of HBcAg in transfected cells was detected by western blot. HBV DNA and RNA from intracellular core particles were examined by Northern and Southern blot analyses. To assess activity of the APOBEC3G in vivo, an HBV vector-based model was used in which APOBEC3G and the HBV vector were co-delivered via high-volume tail vein injection.Levels of HBsAg and HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by ELISA and quantitative PCR analysis respectively.RESULTS: There was a dose dependent decrease in the levels of intracellular core-associated HBV DNA and extracellular production of HBsAg and HBeAg. The levels of intracellular core-associated viral RNA also decreased,but the expression of HBcAg in transfected cells showed almost no change. Consistent with in vitro results,levels of HBsAg in the sera of mice were dramatically decreased. More than 1.5 log10 decrease in levels of serum HBV DNA and liver HBV RNA were observed in the APOBEC3G-treated groups compared with the control groups.CONCLUSION: These findings indicate that APOBEC3G could suppress HBV replication and antigen expression both in vivo and in vitro, promising an advance in treatment of HBV infection.

  18. Retroelements versus APOBEC3 family members: No great escape from the magnificent seven

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    Juan F Arias

    2012-08-01

    Full Text Available Retroelements comprise a large and successful family of transposable genetic elements that, through intensive infiltration, have shaped the genomes of humans and other mammals over millions of years. In fact, retrotransposons now account for approximately 45% of the human genome. Based on their genomic mobility, some retroelements are known to be the cause of genetic diseases, not only in germ and embryonic stem cells but also in somatic cells, posing a threat to genomic stability throughout all cellular populations. In response, mammals have developed intrinsic immunity mechanisms that provide resistance against the threat of the deleterious effects of retrotransposition. Among these, seven members of the APOBEC3 (A3 family of cytidine deaminases serve as highly active, intrinsic, antiretroviral host factors. Certain A3 proteins effectively counteract infections of retroviruses such as HIV-1, as well as those of other virus families, while also blocking the transposition of retroelements. Based on their preferential expression in the germ cells, in which retrotransposons may be active, it is likely that A3 proteins were acquired through mammalian evolution primarily to inhibit retrotransposition and thereby maintain genomic stability in these cells. This review summarizes the recent advances in our understanding of the interplay between the retroelements currently active in the human genome and the anti-retroelement A3 proteins.

  19. First-In-Class Small Molecule Inhibitors of the Single-Strand DNA Cytosine Deaminase APOBEC3G

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    Li, Ming; Shandilya, Shivender M.D.; Carpenter, Michael A.; Rathore, Anurag; Brown, William L.; Perkins, Angela L.; Harki, Daniel A.; Solberg, Jonathan; Hook, Derek J.; Pandey, Krishan K.; Parniak, Michael A.; Johnson, Jeffrey R.; Krogan, Nevan J.; Somasundaran, Mohan; Ali, Akbar; Schiffer, Celia A.; Harris, Reuben S. (Pitt); (UMASS, MED); (SLUHSC); (UCSF); (UMM)

    2012-04-04

    APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. Twenty of 34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions C321-to-L, F, Y, or W mimicked chemical inhibition. A strong specificity for APOBEC3G was evident, as most compounds failed to inhibit the related APOBEC3A enzyme or the unrelated enzymes E. coli uracil DNA glycosylase, HIV-1 RNase H, or HIV-1 integrase. Partial, but not complete, sensitivity could be conferred to APOBEC3A by introducing the entire C321 loop from APOBEC3G. Thus, a structural model is presented in which the mechanism of inhibition is both specific and competitive, by binding a pocket adjacent to the APOBEC3G active site, reacting with C321, and blocking access to substrate DNA cytosines.

  20. Likely role of APOBEC3G-mediated G-to-A mutations in HIV-1 evolution and drug resistance.

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    Patric Jern

    2009-04-01

    Full Text Available The role of APOBEC3 (A3 protein family members in inhibiting retrovirus infection and mobile element retrotransposition is well established. However, the evolutionary effects these restriction factors may have had on active retroviruses such as HIV-1 are less well understood. An HIV-1 variant that has been highly G-to-A mutated is unlikely to be transmitted due to accumulation of deleterious mutations. However, G-to-A mutated hA3G target sequences within which the mutations are the least deleterious are more likely to survive selection pressure. Thus, among hA3G targets in HIV-1, the ratio of nonsynonymous to synonymous changes will increase with virus generations, leaving a footprint of past activity. To study such footprints in HIV-1 evolution, we developed an in silico model based on calculated hA3G target probabilities derived from G-to-A mutation sequence contexts in the literature. We simulated G-to-A changes iteratively in independent sequential HIV-1 infections until a stop codon was introduced into any gene. In addition to our simulation results, we observed higher ratios of nonsynonymous to synonymous mutation at hA3G targets in extant HIV-1 genomes than in their putative ancestral genomes, compared to random controls, implying that moderate levels of A3G-mediated G-to-A mutation have been a factor in HIV-1 evolution. Results from in vitro passaging experiments of HIV-1 modified to be highly susceptible to hA3G mutagenesis verified our simulation accuracy. We also used our simulation to examine the possible role of A3G-induced mutations in the origin of drug resistance. We found that hA3G activity could have been responsible for only a small increase in mutations at known drug resistance sites and propose that concerns for increased resistance to other antiviral drugs should not prevent Vif from being considered a suitable target for development of new drugs.

  1. APOBEC3G impairs the multimerization of the HIV-1 Vif protein in living cells.

    Science.gov (United States)

    Batisse, Julien; Guerrero, Santiago Xavier; Bernacchi, Serena; Richert, Ludovic; Godet, Julien; Goldschmidt, Valérie; Mély, Yves; Marquet, Roland; de Rocquigny, Hugues; Paillart, Jean-Christophe

    2013-06-01

    The HIV-1 viral infectivity factor (Vif) is a small basic protein essential for viral fitness and pathogenicity. Vif allows productive infection in nonpermissive cells, including most natural HIV-1 target cells, by counteracting the cellular cytosine deaminases APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G [A3G]) and A3F. Vif is also associated with the viral assembly complex and packaged into viral particles through interactions with the viral genomic RNA and the nucleocapsid domain of Pr55(Gag). Recently, we showed that oligomerization of Vif into high-molecular-mass complexes induces Vif folding and influences its binding to high-affinity RNA binding sites present in the HIV genomic RNA. To get further insight into the role of Vif multimerization in viral assembly and A3G repression, we used fluorescence lifetime imaging microscopy (FLIM)- and fluorescence resonance energy transfer (FRET)-based assays to investigate Vif-Vif interactions in living cells. By using two N-terminally tagged Vif proteins, we show that Vif-Vif interactions occur in living cells. This oligomerization is strongly reduced when the putative Vif multimerization domain ((161)PPLP(164)) is mutated, indicating that this domain is crucial, but that regions outside this motif also participate in Vif oligomerization. When coexpressed together with Pr55(Gag), Vif is largely relocated to the cell membrane, where Vif oligomerization also occurs. Interestingly, wild-type A3G strongly interferes with Vif multimerization, contrary to an A3G mutant that does not bind to Vif. These findings confirm that Vif oligomerization occurs in living cells partly through its C-terminal motif and suggest that A3G may target and perturb the Vif oligomerization state to limit its functions in the cell. PMID:23576497

  2. Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in both cytidine deaminase domains of Apobec3G.

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    Isabel Uyttendaele

    Full Text Available The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultaneously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization.

  3. Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in both cytidine deaminase domains of Apobec3G.

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    Uyttendaele, Isabel; Lavens, Delphine; Catteeuw, Dominiek; Lemmens, Irma; Bovijn, Celia; Tavernier, Jan; Peelman, Frank

    2012-01-01

    The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultaneously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization. PMID:22970171

  4. Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in breast cancer.

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    Harris, Reuben S

    2015-01-01

    Cancer genomic DNA sequences enable identification of all mutations and suggest targets for precision medicine. The identities and patterns of the mutations themselves also provide critical information for deducing the originating DNA damaging agents, causal molecular mechanisms, and thus additional therapeutic targets. A classic example is ultraviolet light, which crosslinks adjacent pyrimidines and leads to C-to-T transitions. A new example is the DNA cytosine deaminase APOBEC3B, which was identified recently as a source of DNA damage and mutagenesis in breast, head/neck, cervix, bladder, lung, ovary, and to lesser extents additional cancer types. This enzyme is normally an effector protein in the innate immune response to virus infection but upregulation in these cancer types causes elevated levels of genomic C-to-U deamination events, which manifest as C-to-T transitions and C-to-G transversions within distinct DNA trinucleotide contexts (preferentially 5'-TCA and 5'-TCG). Genomic C-to-U deamination events within the same trinucleotide contexts also lead to cytosine mutation clusters (kataegis), and may precipitate visible chromosomal aberrations such as translocations. Clinical studies indicate that APOBEC3B upregulation correlates with poorer outcomes for estrogen receptor-positive breast cancer patients, including shorter durations of disease-free survival and overall survival after surgery. APOBEC3B may therefore have both diagnostic and prognostic potential. APOBEC3B may also be a candidate for therapeutic targeting because inhibition of this non-essential enzyme is predicted to decrease tumor mutation rates and diminish the likelihood of undesirable mutation-dependent outcomes such as recurrence, metastasis, and the development of therapy resistant tumors. PMID:25848704

  5. Characterization of the Catalytic Domain of Human APOBEC3B and the Critical Structural Role for a Conserved Methionine.

    Science.gov (United States)

    Siriwardena, Sachini U; Guruge, Thisari A; Bhagwat, Ashok S

    2015-09-25

    Human APOBEC3B deaminates cytosines in DNA and belongs to the AID/APOBEC family of enzymes. These proteins are involved in innate and adaptive immunity and may cause mutations in a variety of cancers. To characterize its ability to convert cytosines into uracils, we tested several derivatives of APOBEC3B gene for their ability to cause mutations in Escherichia coli. Through this analysis, a methionine residue at the junction of the amino-terminal domain (NTD) and the carboxy-terminal domain (CTD) was found to be essential for high mutagenicity. Properties of mutants with substitutions at this position, examination of existing molecular structures of APOBEC3 family members and molecular modeling suggest that this residue is essential for the structural stability of this family of proteins. The APOBEC3B CTD with the highest mutational activity was purified to homogeneity and its kinetic parameters were determined. Size-exclusion chromatography of the CTD monomer showed that it is in equilibrium with its dimeric form and matrix-assisted laser desorption ionization time-of-flight analysis of the protein suggested that the dimer may be quite stable. The partially purified NTD did not show intrinsic deamination activity and did not enhance the activity of the CTD in biochemical assays. Finally, APOBEC3B was at least 10-fold less efficient at mutating 5-methylcytosine (5mC) to thymine than APOBEC3A in a genetic assay and was at least 10-fold less efficient at deaminating 5mC compared to C in biochemical assays. These results shed light on the structural organization of APOBEC3B catalytic domain, its substrate specificity and its possible role in causing genome-wide mutations.

  6. Production of infectious human immunodeficiency virus type 1 does not require depletion of APOBEC3G from virus-producing cells

    Directory of Open Access Journals (Sweden)

    Goila-Gaur Ritu

    2004-09-01

    Full Text Available Abstract Background The human immunodeficiency virus Vif protein overcomes the inhibitory activity of the APOBEC3G cytidine deaminase by prohibiting its packaging into virions. Inhibition of APOBEC3G encapsidation is paralleled by a reduction of its intracellular level presumably caused by the Vif-induced proteasome-dependent degradation of APOBEC3G. Results In this report we employed confocal microscopy to study the effects of Vif on the expression of APOBEC3G on a single cell level. HeLa cells dually transfected with Vif and APOBEC3G expression vectors revealed efficient co-expression of the two proteins. Under optimal staining conditions approximately 80% of the transfected cells scored double-positive for Vif and APOBEC3G. However, the proportion of double-positive cells observed in identical cultures varied dependent on the fixation protocol and on the choice of antibodies used ranging from as low as 40% to as high as 80% of transfected cells. Importantly, single-positive cells expressing either Vif or APOBEC3G were observed both with wild type Vif and a biologically inactive Vif variant. Thus, the lack of APOBEC3G in some Vif-expressing cells cannot be attributed to Vif-induced degradation of APOBEC3G. These findings are consistent with our results from immunoblot analyses that revealed only moderate effects of Vif on the APOBEC3G steady state levels. Of note, viruses produced under such conditions were fully infectious demonstrating that the Vif protein used in our analyses was both functional and expressed at saturating levels. Conclusions Our results suggest that Vif and APOBEC3G can be efficiently co-expressed. Thus, depletion of APOBEC3G from Vif expressing cells as suggested previously is not a universal property of Vif and thus is not imperative for the production of infectious virions.

  7. Movements of HIV-1 genomic RNA-APOBEC3F complexes and PKR reveal cytoplasmic and nuclear PKR defenses and HIV-1 evasion strategies.

    Science.gov (United States)

    Marin, Mariana; Golem, Sheetal; Kozak, Susan L; Kabat, David

    2016-02-01

    APOBEC3 cytidine deaminases and viral genomic RNA (gRNA) occur in virions, polysomes, and cytoplasmic granules, but have not been tracked together. Moreover, gRNA traffic is important, but the factors that move it into granules are unknown. Using in situ hybridization of transfected cells and protein synthesis inhibitors that drive mRNAs between locales, we observed APOBEC3F cotrafficking with gRNA without altering its movements. Whereas cells with little cytoplasmic gRNA were translationally active and accumulated Gag, suprathreshold amounts induced autophosphorylation of the cytoplasmic double-stranded RNA (dsRNA)-dependent protein kinase (PKR), causing eIF2α phosphorylation, protein synthesis suppression, and gRNA sequestration in stress granules. Additionally, we confirmed recent evidence that PKR is activated by chromosome-associated cellular dsRNAs after nuclear membranes disperse in prophase. By arresting cells in G2, HIV-1 blocks this mechanism for PKR activation and eIF2α phosphorylation. However, cytopathic membrane damage in CD4- and coreceptor-positive cultures infected with laboratory-adapted fusogenic HIV-1LAI eventually enabled PKR entry and activation in interphase nuclei. These results reveal multiple stages in the PKR-HIV-1 battleground that culminate in cell death. We discuss evidence suggesting that HIV-1s evolve in vivo to prevent or delay PKR activation by all these mechanisms. PMID:26626364

  8. Prokaryotic Expression and Purification of HIV-1 Vif and hAPOBEC3G, Preparation of Polyclonal Antibodies

    Institute of Scientific and Technical Information of China (English)

    Lan LI; Yi-shu YANG; Ze-lin LI; Yi ZENG

    2008-01-01

    To prepare HIV-1 Vif and hAPOBEC3G and to produce their antibodies, the full length gene fragment of HIV-1 Vif was amplified by PCR from a plasmid of HIV-1 NL4.3 cDNA, and the APOBEC3G gene was obtained by RT-PCR from the total RNA of H9 cells. The resulting DNA construct was cloned into a prokaryotic expression vector (pET-32a). Recombinant pET-vif and pET-APOBEC3G were expressed respectively in Eserichia coli BL21 (DE3) as an insoluble protein. The vector also contained a six-histidine tag at the C-terminus for convenient purification and detection. To express and purify the HIV-1 Vif and hAPOBEC3G in E. coli cells, the accuracy of inserted gene and specificity of proteins were detected by the two enzyme digestion method, SDS-PAGE, and Western blotting. Rabbits were then immunized by Vif or APOBEC3G protein and serum samples were tested by indirect ELISA to determine the level of antibodies. Immunoenzyme and immunofluorescence assays were performed to identify the specificity of polyclonal antibodies. The titer of the anti-Vif antibodies was 1:204800, and that of the anti-APOBEC3G antibodies was 1:102400. Thus the antibodies could detect the antigen expression in the cells, demonstrating that fusion proteins with high purity and their corresponding polyclonal antibodies with high titer and specificity were achieved.

  9. Human APOBEC3G-mediated hypermutation is associated with antiretroviral therapy failure in HIV-1 subtype C-infected individuals

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    Anita Shet

    2013-02-01

    Full Text Available Introduction: Human APOBEC3G/F (hA3G/F restricts retroviral replication through G-to-A hypermutations, which can generate drug-resistant progenies in vitro. The clinical relevance is still inconclusive. To bridge this gap, we aim to study the role of these hypermutations in evolution of drug resistance; we characterised hA3G/F-mediated hypermutations in the RT region of the pol gene of patients with or without antiretroviral therapy (ART. Methods: In 88 HIV-1-positive individuals, drug resistance genotyping was carried out in plasma virus and provirus by population sequencing. Hypermutations were determined by three different approaches using Hypermut 2.0 software, cluster analysis and APOBEC3G-mediated defectives indices. Clinical and demographic characteristics of these individuals were studied in relation to these hypermutations. Results: hA3G/F-mediated hypermutated sequences in proviral DNA, but not in plasma virus, were identified in 11.4% (10/88 subjects. Proviral hypermutations were observed more frequently in patients with ART failure than in ART-naïve individuals (p=0.03. In therapy failure patients, proviral hypermutation were associated with greater intra-compartmental genetic diversity (p<0.001. In therapy-naïve individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. Only a limited concordance was found between the drug resistance mutations in plasma RNA and proviral DNA. Conclusions: hA3G lethal hypermutation was significantly associated with ART failure in Indian HIV-1 subtype C patients. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo.

  10. SAMHD1——A HIV-1 restriction factor derived from myeloid lineage monocytes%髓系单核细胞来源的HIV-1限制性因子——SAMHD1

    Institute of Scientific and Technical Information of China (English)

    李佩璐; 陈倩倩; 张驰宇

    2012-01-01

    天然抗病毒限制因子是HIV-1研究最热点的领域.继APOBEC3G、Trim5α、Tetherin被发现之后,SAMHD1于2011年被发现为新的抗HIV-1限制因子.它主要在髓系来源的单核细胞中表达,如巨噬细胞和树突状细胞.该文对SAMHD1的结构、抗病毒机制、与Vpx的相互作用以及进化等方面的研究进行了综述.SAMHD1的发现为深入研究SAMHD1在慢病毒致病机理中作用打开了一扇门.%HIV-1 restriction factors have became one of the hottest fields of AIDS researches. In 2011, SAMHD1 was demonstrated to be a novel HIV-1 restriction factor, adding to a list of HIV-1 restriction factors that include APOBEC3G, TRIM5a and Tetherin. SAMHD1 is highly expressed in myeloid-lineage monocytes, such as macrophages and dendritic cells. In this paper, we review the current research progress on the structure of SAMHD1, its antiviral mechanism, interaction with the lentivirus Vpx, and evolution. The identification of SAMHD1 opens the door towards understanding the role of SAMHD1 in lentiviral pathogenesis.

  11. APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer

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    Manikandan Periyasamy

    2015-10-01

    Full Text Available Estrogen receptor α (ERα is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER and to repair by non-homologous end-joining (NHEJ pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action.

  12. N-terminal and C-terminal cytosine deaminase domain of APOBEC3G inhibit hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    Yan-Chang Lei; Dong-Liang Yang; Yong-Jun Tian; Hong-Hui Ding; Bao-Ju Wang; Yan Yang; You-Hua Hao; Xi-Ping Zhao; Meng-Ji Lu; Fei-Li Gong

    2006-01-01

    AIM: To investigate the effect of human apolipoprotein B mRNA-editing enzyme catalytic-polypeptide 3G(APOBEC3G) and its N-terminal or C-terminal cytosine deaminase domain-mediated antiviral activity against hepatitis B virus (HBV) in vitro and in vivo.METHODS: The mammalian hepatoma cells HepG2 and HuH7 were cotransfected with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vector and 1.3-fold-overlength HBV DNA as well as the linear monomeric HBV of genotype B and C. For in vivo study, an HBV vector-based mouse model was used in which APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vectors were co-delivered with 1.3-fold-overlength HBV DNA via high-volume tail vein injection. Levels of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) in the media of the transfected cells and in the sera of mice were determined by ELISA.The expression of hepatitis B virus core antigen (HBcAg)in the transfected cells was determined by Western blot analysis. Core-associated HBV DNA was examined by Southern blot analysis. Levels of HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by quantitative PCR and quantitative RT-PCR analysis, respectively.RESULTS: Human APOBEC3G exerted an anti-HBV activity in a dose-dependent manner in HepG2 cells,and comparable suppressive effects were observed on genotype B and C as that of genotype A. Interestingly,the N-terminal or C-terminal cytosine deaminase domain alone could also inhibit HBV replication in HepG2 cells as well as Huh7 cells. Consistent with in vitro results, the levels of HBsAg in the sera of mice were dramatically decreased, with more than 50 times decrease in the levels of serum HBV DNA and core-associated RNA in the liver of mice treated with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain as compared to the controls.CONCLUSION: Our findings provide probably the first

  13. 宿主细胞对HIV-1复制的限制性%The host restriction factors targeted HIV-1 replication

    Institute of Scientific and Technical Information of China (English)

    贾彦辉; 徐庆刚

    2013-01-01

    HIV-1感染的主要靶细胞是宿主的CD4+T淋巴细胞,使宿主的免疫机能下降.在HIV-1与宿主的长期进化中,它们之间逐渐形成了复杂的入侵与反入侵关系.人类已经进化出多种机制来抵制HIV-1的感染和复制.宿主细胞内的限制性因子是抑制HIV-1复制的主要机制之一,也是研究人员比较关注的一类机制.SAMHD1作为最新发现的一个限制性因子,成为一个研究热点.通过阐述SAMHD1,APOBEC3G/F,TRIM5α及Tetherin在HIV-1复制中的关键作用,了解宿主细胞对病毒感染的限制性,有助于理解宿主与病毒之间的抗衡关系,宿主抗病毒机制,为治疗HIV-1寻找新的靶点.%The CD4 + T cells are the most important targeted cells of HIV-1 infection leading to immunity dysfunction.A long history of human infection by HIV-1 has resulted in complicated relationship between human and HIV-1.Among the many mechanisms to inhibit HIV-1 infection and replication in human,the host restriction factors are an attentive mechanism.Recently,researchers pay much attention to SAMHD1 which is a new discovered restriction factor.This review mainly discussed the effect of SAMHD1,APOBEC3G/ F,TRIM5α and Tetherin on HIV-1 life cycle.Description of HIV-1 restriction in host cells helps us to understand viral pathogenesis and searching for a new antiviral strategy.

  14. Cellular Restriction Factors of Feline Immunodeficiency Virus

    OpenAIRE

    Carsten Münk; Jörg Zielonka

    2011-01-01

    Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating...

  15. Catalytic analysis of APOBEC3G involving real-time NMR spectroscopy reveals nucleic acid determinants for deamination.

    Directory of Open Access Journals (Sweden)

    Keisuke Kamba

    Full Text Available APOBEC3G (A3G is a single-stranded DNA-specific cytidine deaminase that preferentially converts cytidine to uridine at the third position of triplet cytosine (CCC hotspots. A3G restricts the infectivity of viruses, such as HIV-1, by targeting CCC hotspots scattered through minus DNA strands, reverse-transcribed from genomic RNA. Previously, we developed a real-time NMR method and elucidated the origin of the 3'→5' polarity of deamination of DNA by the C-terminal domain of A3G (CD2, which is a phenomenon by which a hotspot located closer to the 5'-end is deaminated more effectively than one less close to the 5'-end, through quantitative analysis involving nonspecific binding to and sliding along DNA. In the present study we applied the real-time NMR method to analyze the catalytic activity of CD2 toward DNA oligonucleotides containing a nucleotide analog at a single or multiple positions. Analyses revealed the importance of the sugar and base moieties throughout the consecutive 5 nucleotides, the CCC hotspot being positioned at the center. It was also shown that the sugar or base moieties of the nucleotides outside this 5 nucleotide recognition sequence are also relevant as to CD2's activity. Analyses involving DNA oligonucleotides having two CCC hotspots linked by a long sequence of either deoxyribonucleotides, ribonucleotides or abasic deoxyribonucleotides suggested that the phosphate backbone is required for CD2 to slide along the DNA strand and to exert the 3'→5' polarity. Examination of the effects of different salt concentrations on the 3'→5' polarity indicated that the higher the salt concentration, the less prominent the 3'→5' polarity. This is most likely the result of alleviation of sliding due to a decrease in the affinity of CD2 with the phosphate backbone at high salt concentrations. We also investigated the reactivity of substrates containing 5-methylcytidine (5mC or 5-hydroxymethylcytidine, and found that A3G exhibited low

  16. Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity

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    Strebel Klaus

    2007-08-01

    Full Text Available Abstract Background APOBEC3 (A3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (CDA, unlike A3G, which has a second N-terminal CDA previously found to be important for Vif sensitivity and virus encapsidation. A3A is packaged into HIV-1 virions but, unlike A3G, does not have antiviral properties. Here, we investigated the reason for the lack of A3A antiviral activity. Results Sequence alignment of A3G and A3A revealed significant homology of A3A to the C-terminal region of A3G. However, while A3G co-purified with detergent-resistant viral nucleoprotein complexes (NPC, virus-associated A3A was highly detergent-sensitive leading us to speculate that the ability to assemble into NPC may be a property conveyed by the A3G N-terminus. To test this model, we constructed an A3G-3A chimeric protein, in which the N-terminal half of A3G was fused to A3A. Interestingly, the A3G-3A chimera was packaged into HIV-1 particles and, unlike A3A, associated with the viral NPC. Furthermore, the A3G-3A chimera displayed strong antiviral activity against HIV-1 and was sensitive to inhibition by HIV-1 Vif. Conclusion Our results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity.

  17. Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B.

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    Monica K Akre

    Full Text Available Molecular, cellular, and clinical studies have combined to demonstrate a contribution from the DNA cytosine deaminase APOBEC3B (A3B to the overall mutation load in breast, head/neck, lung, bladder, cervical, ovarian, and other cancer types. However, the complete landscape of mutations attributable to this enzyme has yet to be determined in a controlled human cell system. We report a conditional and isogenic system for A3B induction, genomic DNA deamination, and mutagenesis. Human 293-derived cells were engineered to express doxycycline-inducible A3B-eGFP or eGFP constructs. Cells were subjected to 10 rounds of A3B-eGFP exposure that each caused 80-90% cell death. Control pools were subjected to parallel rounds of non-toxic eGFP exposure, and dilutions were done each round to mimic A3B-eGFP induced population fluctuations. Targeted sequencing of portions of TP53 and MYC demonstrated greater mutation accumulation in the A3B-eGFP exposed pools. Clones were generated and microarray analyses were used to identify those with the greatest number of SNP alterations for whole genome sequencing. A3B-eGFP exposed clones showed global increases in C-to-T transition mutations, enrichments for cytosine mutations within A3B-preferred trinucleotide motifs, and more copy number aberrations. Surprisingly, both control and A3B-eGFP clones also elicited strong mutator phenotypes characteristic of defective mismatch repair. Despite this additional mutational process, the 293-based system characterized here still yielded a genome-wide view of A3B-catalyzed mutagenesis in human cells and a system for additional studies on the compounded effects of simultaneous mutation mechanisms in cancer cells.

  18. Real Moments of the Restrictive Factor

    Indian Academy of Sciences (India)

    Andrew Ledoan; Alexandru Zaharescu

    2009-09-01

    Let be a real number such that 0 < < 1. We establish asymptotic formulas for the weighted real moments $\\sum_{n≤ x}R^(n)(1-n/x)$, where $R(n)=\\prod^k_{v=1}p^{ v-1}_v$ is the Atanassov strong restrictive factor function and $n=\\prod^k_{v=1}p^{ v}_v$ is the prime factorization of .

  19. RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates

    OpenAIRE

    Polevoda, Bogdan; McDougall, William M.; Tun, Bradley N.; Cheung, Michael; Salter, Jason D.; Friedman, Alan E.; Smith, Harold C.

    2015-01-01

    APOBEC3G (A3G) DNA deaminase activity requires a holoenzyme complex whose assembly on nascent viral reverse transcripts initiates with A3G dimers binding to ssDNA followed by formation of higher-order A3G homo oligomers. Catalytic activity is inhibited when A3G binds to RNA. Our prior studies suggested that RNA inhibited A3G binding to ssDNA. In this report, near equilibrium binding and gel shift analyses showed that A3G assembly and disassembly on ssDNA was an ordered process involving A3G d...

  20. Lower HIV provirus levels are associated with more APOBEC3G protein in blood resting memory CD4+ T lymphocytes of controllers in vivo.

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    Mariapia De Pasquale

    Full Text Available Immunodeficiency does not progress for prolonged periods in some HLA B57- and/or B27-positive subjects with human immunodeficiency virus type 1 (HIV infection, even in the absence of antiretroviral therapy (ART. These "controllers" have fewer HIV provirus-containing peripheral blood mononuclear cells than "non-controller" subjects, but lymphocytes that harbor latent proviruses were not specifically examined in studies to date. Provirus levels in resting memory cells that can serve as latent reservoirs of HIV in blood were compared here between controllers and ART-suppressed non-controllers. APOBEC3G (A3G, a cellular factor that blocks provirus formation at multiple steps if not antagonized by HIV virion infectivity factor (Vif, was also studied. HLA-linked HIV control was associated with less provirus and more A3G protein in resting CD4+ T central memory (Tcm and effector memory (Tem lymphocytes (provirus: p = 0.01 for Tcm and p = 0.02 for Tem; A3G: p = 0.02 for Tcm and p = 0.02 for Tem. Resting memory T cells with the highest A3G protein levels (>0.5 RLU per unit of actin had the lowest levels of provirus (<1,000 copies of DNA per million cells in vivo (p = 0.03, Fisher's exact test. Using two different experimental approaches, Vif-positive viruses with more A3G were found to have decreased virion infectivity ex vivo. These results raise the hypothesis that HIV control is associated with increased cellular A3G that may be packaged into Vif-positive virions to add that mode of inhibition of provirus formation to previously described adaptive immune mechanisms for HIV control.

  1. Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins.

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    Wenyan Zhang

    Full Text Available BACKGROUND: APOBEC3G (A3G and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized. METHODS AND FINDINGS: In the present study, we have demonstrated that the regions of APOBEC3F (A3F that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE. CONCLUSIONS: Our data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors.

  2. Insights into the dual activity of SIVmac239 Vif against human and African green monkey APOBEC3G.

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    Ritu Gaur

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 Vif is essential for viral evasion of the host antiviral protein APOBEC3G (APO3G. The Vif protein from a distantly related African green monkey (Agm simian immunodeficiency virus (SIVagm is unable to suppress the antiviral activity of human APO3G but is active against Agm APO3G. SIVmac Vif on the other hand, possesses antiviral activity against both human and Agm APO3G. In this study, we were interested in mapping domains in SIVmac Vif that are responsible for its dual activity against human and Agm APO3G. We constructed a series of Vif chimeras by swapping domains in SIVmac Vif with equivalent regions from SIVagm Vif and determined their activity against human and Agm APO3G. We found that replacing any region in SIVmac Vif by corresponding fragments from SIVagm Vif only moderately reduced the activity of the chimeras against Agm APO3G but in all cases resulted in a severe loss of activity against human APO3G. These results suggest that the domains in SIVmac Vif required for targeting human and Agm APO3G are distinct and cannot be defined as linear amino acid motifs but rather appear to depend on the overall structure of full-length SIVmac Vif.

  3. An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals

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    Münk Carsten

    2012-05-01

    Full Text Available Abstract Background The APOBEC3 (A3 genes play a key role in innate antiviral defense in mammals by introducing directed mutations in the DNA. The human genome encodes for seven A3 genes, with multiple splice alternatives. Different A3 proteins display different substrate specificity, but the very basic question on how discerning self from non-self still remains unresolved. Further, the expression of A3 activity/ies shapes the way both viral and host genomes evolve. Results We present here a detailed temporal analysis of the origin and expansion of the A3 repertoire in mammals. Our data support an evolutionary scenario where the genome of the mammalian ancestor encoded for at least one ancestral A3 gene, and where the genome of the ancestor of placental mammals (and possibly of the ancestor of all mammals already encoded for an A3Z1-A3Z2-A3Z3 arrangement. Duplication events of the A3 genes have occurred independently in different lineages: humans, cats and horses. In all of them, gene duplication has resulted in changes in enzyme activity and/or substrate specificity, in a paradigmatic example of convergent adaptive evolution at the genomic level. Finally, our results show that evolutionary rates for the three A3Z1, A3Z2 and A3Z3 motifs have significantly decreased in the last 100 Mya. The analysis constitutes a textbook example of the evolution of a gene locus by duplication and sub/neofunctionalization in the context of virus-host arms race. Conclusions Our results provide a time framework for identifying ancestral and derived genomic arrangements in the APOBEC loci, and to date the expansion of this gene family for different lineages through time, as a response to changes in viral/retroviral/retrotransposon pressure.

  4. Restricting factors of the development of SEA in China

    Institute of Scientific and Technical Information of China (English)

    Wang Xianghua; Zhu Xiaodong; LiYangfan; Chen Shanshan

    2006-01-01

    "Environmental Impact Assessment Law of P. R. China" was promulgated on Oct. 28th, 2002 and has been put into effect on Sep 1st, 2003. This paper puts forward some important factors which restrict the development of Strategic Environmental Assessment according to the preliminary practices of SEA in China. These restricting factors are: (1) potential resistance from some departments; (2) poor cooperation between different departments; (3) limited availability of information resources; (4) lack of well-developed SEA methods; (5) difficulties in public participation. The primary thought to solve these problems were proposed at policy and technique level.

  5. Molecular modeling of human APOBEC3G to predict the binding modes of the inhibitor compounds IMB26 and IMB35

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    Zhixin Zhang

    2013-07-01

    Full Text Available APOBEC3G(A3G is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication. The virally encoded protein Vif binds to A3G and induces its degradation, thereby counteracting the antiviral activity of A3G. Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development. Currently, there is an urgent need for understanding the three dimensional structure of full-length A3G. In this work, we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2 (APO2 and the catalytic domain structure of A3G. Two compounds, IMB26 and IMB35, which have been shown to bind to A3G and block degradation by Vif, were docked into the A3G model and the binding modes were generated for further analysis. The results may be used to design or optimize molecules targeting Vif–A3G interaction, and lead to the development of novel anti-HIV drugs.

  6. Cacao in México: Restrictive factors and productivity levels

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    Julio Díaz-José

    2014-12-01

    Full Text Available Cacao (Theobroma cacao L. represents one of the most important agricultural crops of the humid Mexican tropics. In the last 10 yr, approximately 23.000 t of this grain were no longer produced per cycle. The objective of this study was to identify characteristics and factors that restrict production in the states of Tabasco and Chiapas. A survey was applied to obtain information about 184 producers and their plantations by two-stage sampling. Descriptive statistics were calculated and multilevel models were adjusted to analyze the information. Results show that there are differences (P < 0.05 in cacao yield between municipalities (380 kg ha-1 + u,o j is the estimated residual for each municipality. Crop productivity levels are higher in the state of Tabasco than in Chiapas (644 and 344 kg ha-1, respectively. Incidence of frosty pod rot of cacoa, also known as moniliasis, induced by Moniliophthora roreri [(Cif H.C. Evans, Stalpers, Samson & Benny 1978] is significantly greater (P < 0.05 in the state of Chiapas (60% than in Tabasco (48%.Producers who carry out more crop management practices increase yields and decrease the pathogen's impact on their plantations. Results suggest the need to apply differentiated public policies to promote production within each region or municipality.

  7. Restricting Factors at Modification of Parameters of Associative Engineering Objects

    Science.gov (United States)

    Horváth, László

    Advancements in product development have reached full integration of engineering activities and processes in product lifecycle management (PLM) systems. PLM systems are based on high-level modeling, simulation and data management. Despite significant development of modeling in PLM systems, a strong demand was recognized for improved decision assistance in product development. Decision assistance can be improved by application of methods from the area of computer intelligence. In order for a product development company to stay competitive, it is important for its modeling system to be relied on local even personal knowledge. The authors analyzed current PLM systems for shortcomings and possibilities for extended intelligence at decision-making during product development. They propose methods in order to increase suitability of current modeling systems to accommodate knowledge based IT at definition of sets of parameters of modeled objects and in the management of frequent changes of modeled objects. In the center of the proposed methodology, constrained parameters act as restricting factors at definition and modification of parameters of associative engineering objects. Paper starts with an outlook to modeling in current engineering systems and preliminary results by the authors. Following this, groups of essential information as handled by he proposed modeling are summarized and procedures for processing of that groups of information are detailed. Next, management of chains of changes along chains of associa-tive product objects and a new style of decision assistance in modeling systems are explained. Changes are created or verified by behavior analysis. Finally, behavior analysis, human intent combination, product data view creation, and change management are discussed as the proposed integrated and coordinated methodology for enhanced support of decision-making in product development.

  8. A Study of Evaluation System of Restricting Factors in Training Students' Qualities

    Institute of Scientific and Technical Information of China (English)

    MA Xiao-yan

    2002-01-01

    This paper studies evaluation system of restricting factors in training students' qualities by modern mathematical method of analysis hierarchy process and principal factor analysis, and to build up a mathematical model of evaluation system.

  9. Computation of the pseudoskin factor for a restricted-entry well

    Energy Technology Data Exchange (ETDEWEB)

    Ding, W. (Joshi Technologies International Inc., Tulsa, OK (United States)); Reynolds, A.C. Jr. (Univ. of Tulsa, OK (United States))

    1994-03-01

    Wells frequently are completed over a fraction of the oil zone to delay water and gas coning. This type of completion is called a restricted-entry or partially penetrating well. When analyzing well-test data from a restricted-entry well, semilog analysis of pseudoradial flow data yields an estimate of the total skin factor, which is a linear combination of the mechanical skin factor and the pseudoskin factor caused by restricted entry. This work presented two new equations for computing the pseudoskin factor from a restricted-entry well completed in a multilayer reservoir. These equations represent generalization of formulas presented by Papatzacos and Vrbik for single-layer homogeneous reservoirs. For ranges of reservoir and well parameters ordinarily encountered, the new equations provide results approximately equal to those obtained from the Yeh-Reynolds calculation procedure, but are easier to use than this equation.

  10. Factors associated with parental use of restrictive feeding practices to control their children's food intake.

    Science.gov (United States)

    Gray, Wendy N; Janicke, David M; Wistedt, Kristin M; Dumont-Driscoll, Marilyn C

    2010-10-01

    There is a critical need to identify risk factors that make parents more likely to restrict their child's food intake. Child weight and ethnicity, parent weight, parent body dissatisfaction, and parent concern of child weight were examined as correlates of parent use of restrictive feeding practices in a diverse sample of 191 youth (ages 7-17). Participants attending a pediatric outpatient visit completed the Child Feeding Questionnaire (parent feeding practices and beliefs), the Figure Rating Scale (body dissatisfaction) and a demographic form. Parent BMI and child degree of overweight were calculated. Parent use of restrictive feeding practices was positively associated with parent BMI and was moderated by parent body dissatisfaction. Parent concern of child weight mediated the relationship between increasing child degree of overweight and parent use of restrictive feeding practices. There were no differences by child gender or ethnicity in parent use of restrictive feeding practices. These preliminary findings highlight the importance of assessing for underlying parent motivations for utilizing restrictive feeding practices and may help to identify and intervene with families at-risk for engaging in counterproductive weight control strategies. Continued identification of correlates of parent use of restrictive feeding practices is needed across child development and among individuals from diverse backgrounds. PMID:20633586

  11. Restrictive Factors of Vocational Education Development in Cultivation of Rural Practical Skilled Personnel and Countermeasures

    OpenAIRE

    Wang, Ning; Liu, Fang

    2014-01-01

    Kunming City is accelerating the process of agricultural modernization, industrialization, informationization and ecological development. In this process, it needs speeding up building new high level and advanced rural practical skilled personnel team suitable for development demand. By empirical analysis method, this paper discussed the factors restricting vocational education in cultivation of rural practical skilled personnel. Then, it came up with countermeasures in cultivation objective ...

  12. The function and evolution of the restriction factor viperin in primates was not driven by lentiviruses

    Directory of Open Access Journals (Sweden)

    Lim Efrem S

    2012-06-01

    Full Text Available Abstract Background Viperin, also known as RSAD2, is an interferon-inducible protein that potently restricts a broad range of different viruses such as influenza, hepatitis C virus, human cytomegalovirus and West Nile virus. Viperin is thought to affect virus budding by modification of the lipid environment within the cell. Since HIV-1 and other retroviruses depend on lipid domains of the host cell for budding and infectivity, we investigated the possibility that Viperin also restricts human immunodeficiency virus and other retroviruses. Results Like other host restriction factors that have a broad antiviral range, we find that viperin has also been evolving under positive selection in primates. The pattern of positive selection is indicative of Viperin's escape from multiple viral antagonists over the course of primate evolution. Furthermore, we find that Viperin is interferon-induced in HIV primary target cells. We show that exogenous expression of Viperin restricts the LAI strain of HIV-1 at the stage of virus release from the cell. Nonetheless, the effect of Viperin restriction is highly strain-specific and does not affect most HIV-1 strains or other retroviruses tested. Moreover, knockdown of endogenous Viperin in a lymphocytic cell line did not significantly affect the spreading infection of HIV-1. Conclusion Despite positive selection having acted on Viperin throughout primate evolution, our findings indicate that Viperin is not a major restriction factor against HIV-1 and other retroviruses. Therefore, other viral lineages are likely responsible for the evolutionary signatures of positive selection in viperin among primates.

  13. Automobile Driving in Older Adults: Factors Affecting Driving Restriction in Men and Women

    OpenAIRE

    MARIE-DIT-ASSE, Laetitia; Fabrigoule, Colette; Helmer, Catherine; Laumon, Bernard; Lafont, Sylviane

    2014-01-01

    OBJECTIVES: To identify factors associated with driving restriction in elderly men and women. DESIGN: Prospective cohort study of French drivers from 2003 to 2009. SETTING: The Three-City Cohort of Bordeaux, a prospective study of 2,104 people aged 65 and older. PARTICIPANTS: Five hundred twenty-three drivers with a mean age of 76 (273 male, 250 female). MEASUREMENTS: Sociodemographic characteristics, driving habits, health variables, cognitive evaluation and dementia diagnosis. Predementia w...

  14. Macrophage Migration Inhibitory Factor in Fetoplacental Tissues from Preeclamptic Pregnancies with or without Fetal Growth Restriction

    OpenAIRE

    Roberta Romagnoli; Tullia Todros; Ettore Piccoli; Alessandro Rolfo; Elena Vasario; Mario Castellucci; Francesca Ietta; Daniela Marzioni; Simona Cardaropoli; Luana Paulesu

    2012-01-01

    The proinflammatory cytokine MIF (macrophage migration inhibitory factor) is involved in physiological and pathological processes in pregnancy. MIF maternal serum levels are increased in preeclampsia (PE). We hypothesize that pregnancy tissues are the source of MIF overexpression in PE. MIF protein was studied in maternal sera, placental tissues, fetal membranes, and umbilical cord of 8 control and 20 PE pregnancies: 10 with normal fetal growth (PE-AGA) and 10 with fetal growth restriction (P...

  15. Dual roles of lineage restricted transcription factors: the case of MITF in melanocytes.

    Science.gov (United States)

    Levy, Carmit; Fisher, David E

    2011-01-01

    Microphthalmia-associated Transcription Factor, MITF, is a master regulator of melanocyte development, differentiation, migration, and survival.(1) A broad collection of studies have indicated that MITF directly regulates the transcription of genes involved in pigmentation, which are selective to the melanocyte lineage. In addition, MITF controls expression of genes which are expressed in multiple cell lineages, and may also play differential roles in activating vs. maintaining gene expression patterns. In this Point of View article, we discuss lineage restricted transcription factor activation of both tissue-specific and ubiquitously expressed genes using melanocytes and MITF as a model system that may eventually provide insights into such processes in multiple cell lineages.

  16. Low proviral small ruminant lentivirus load as biomarker of natural restriction in goats.

    Science.gov (United States)

    Crespo, Helena; Bertolotti, Luigi; Proffiti, Margherita; Cascio, Paolo; Cerruti, Fulvia; Acutis, Pier Luigi; de Andrés, Damián; Reina, Ramsés; Rosati, Sergio

    2016-08-30

    Small ruminant lentiviruses (SRLV) globally affect welfare and production of sheep and goats and are mainly controlled through elimination of infected animals, independently of the viral kinetics within the single animal. Control programs are based on highly sensitive serological tests, however the existence of low antibody responders leads to the permanent presence of seronegative infected animals in the flock, thus perpetuating the infection. On the other hand, long-term non-progressors show a detectable antibody response not indicative of a shedding animal, suggesting immune contention of infection. In this study, we analyse two goat populations within the same herd, harbouring low or high proviral SRLV loads respectively, both showing a robust antibody response. In vivo findings were confirmed in vitro since fibroblastic cell lines obtained from one high and one low proviral load representative goats, showed respectively a high and a faint production of virus upon infection with reference and field circulating SRLV strains. Differences in virus production were relieved when strain CAEV-Co was used for experimental infection. We analysed LTR promoter activity, proviral load, entry step and production of virus and viral proteins. Intriguingly, proteasomal activity was higher in fibroblasts from low proviral load animals and proteasome inhibition increased viral production in both cell lines, suggesting the implication of active proteasome-dependent restriction factors. Among them, we analysed relative expression and sequences of TRIM5α, APOBEC3 (Z1, Z2, Z3 and Z2-Z3) and BST-2 (Tetherin) and found a global antiviral status in low proviral carriers that may confer protection against viral shedding and disease onset. PMID:27527777

  17. Sequestration of Vascular Endothelial Growth Factor (VEGF Induces Late Restrictive Lung Disease.

    Directory of Open Access Journals (Sweden)

    Minna M Wieck

    Full Text Available Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF, which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function.To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function.Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1 were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model.Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes.These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions.

  18. Quantification and control of restrictive ecological factors in acidogenic de-sulfate bioreactor

    Institute of Scientific and Technical Information of China (English)

    王爱杰; 任南琪

    2002-01-01

    As an artificial microbial ecosystem, acidogenic de-sulfate bioreactor has high efficiency of sulfate removal. The restrictive ecological factors, including causing ecological factors, such as COD/SO42- ratio and sulfate loading rate (Ns), and following ecological factors, such as pH value, oxidation reduction potential (ORP) and alkalinity (ALK) have significant effect on the ability and stability of acidogenic de-sulfate bio-reactor. Continuous flow and batch test were carried out to investigate the quantification and control of COD/SO42- ratio, Ns, pH value, ORP and ALK in acidogenic de-sulfate bioreactor supplied with molasses wastewater as sole organic carbon source and sodium sulfate as electron donor. It was demonstrated that In order to maintain high sulfate removal rate (SRR) of 80% to 90%, the restrictive factors should meet all the requirement as follows: kCOD/ SO42- ratio≥2.0, Ns≤7.5 kg (m3·d)-1,pH=5.7~6.2,ORP=-320~-420 mV and ALK=1 500~2 000 mg/L.

  19. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Directory of Open Access Journals (Sweden)

    Debrah A Fine

    Full Text Available The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.

  20. Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

    Science.gov (United States)

    Padi, Megha; Korkhin, Anna; James, Robert L.; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A.; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A.; Hill, David E.; Cusick, Michael E.; Vidal, Marc; Florens, Laurence; Washburn, Michael P.; Litovchick, Larisa; DeCaprio, James A.

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  1. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.

    Science.gov (United States)

    Fine, Debrah A; Rozenblatt-Rosen, Orit; Padi, Megha; Korkhin, Anna; James, Robert L; Adelmant, Guillaume; Yoon, Rosa; Guo, Luxuan; Berrios, Christian; Zhang, Ying; Calderwood, Michael A; Velmurgan, Soundarapandian; Cheng, Jingwei; Marto, Jarrod A; Hill, David E; Cusick, Michael E; Vidal, Marc; Florens, Laurence; Washburn, Michael P; Litovchick, Larisa; DeCaprio, James A

    2012-01-01

    The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT. PMID:23093934

  2. Model identification with BPNN on restrictive ecological factors of SRB for sulfate-reduction

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The model of back-propagation neural network(BPNN)was presented to demonstrate the effect of restrictive ecological factors,COD/SO42-ratio,pH value,alkalinity(ALK)and SO42-loading rate(Ns),on sulfate-reduction of Sulfate Reducing Bacteria(SRB)in an acidogenic sulfate-reducing reactor supplied with molasses as sole organic carbon source and sodium sulfate as electron acceptor.The compare of experimental results and computer simulation was also discussed.It was shown that the method of BPNN had a powerful ability to analyze the ecological characteristic of acidogenic sulfate-reducing ecosystem quantitatively.

  3. Restrictive Factors of Vocational Education Development in Cultivation of Rural Practical Skilled Personnel and Countermeasures

    Institute of Scientific and Technical Information of China (English)

    Ning; WANG; Fang; LIU

    2014-01-01

    Kunming City is accelerating the process of agricultural modernization,industrialization,informationization and ecological development. In this process,it needs speeding up building new high level and advanced rural practical skilled personnel team suitable for development demand. By empirical analysis method,this paper discussed the factors restricting vocational education in cultivation of rural practical skilled personnel. Then,it came up with countermeasures in cultivation objective of rural vocational education,arrangement of specialized disciplines,key development tasks,and establishment of diversified investment system.

  4. Demand Forecasting at Low Aggregation Levels using Factored Conditional Restricted Boltzmann Machine

    DEFF Research Database (Denmark)

    Mocanu, Elena; Nguyen, Phuong H.; Gibescu, Madeleine;

    2016-01-01

    approaches have been proposed in the literature. As an evolution of neural network-based prediction methods, deep learning techniques are expected to increase the prediction accuracy by allowing stochastic formulations and bi-directional connections between neurons. In this paper, we investigate a newly...... developed deep learning model for time series prediction, namely Factored Conditional Restricted Boltzmann Machine (FCRBM), and extend it for electrical demand forecasting. The assessment is made on the EcoGrid dataset, originating from the Bornholm island experiment in Denmark, consisting of aggregated......The electrical demand forecasting problem can be regarded as a nonlinear time series prediction problem depending on many complex factors since it is required at various aggregation levels and at high temporal resolution. To solve this challenging problem, various time series and machine learning...

  5. Analysis of the restricting factors of laser countermeasure active detection technology

    Science.gov (United States)

    Zhang, Yufa; Sun, Xiaoquan

    2016-07-01

    The detection effect of laser active detection system is affected by various kinds of factors. In view of the application requirement of laser active detection, the influence factors for laser active detection are analyzed. The mathematical model of cat eye target detection distance has been built, influence of the parameters of laser detection system and the environment on detection range and the detection efficiency are analyzed. Various parameters constraint detection performance is simulated. The results show that the discovery distance of laser active detection is affected by the laser divergence angle, the incident angle and the visibility of the atmosphere. For a given detection range, the laser divergence angle and the detection efficiency are mutually restricted. Therefore, in view of specific application environment, it is necessary to select appropriate laser detection parameters to achieve optimal detection effect.

  6. Computation of the pseudoskin factor caused by a restricted-entry well completed in a multilayer reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, N.; Reynolds, A.C.

    1989-06-01

    This work considers flow to a restricted-entry well in a single- or multilayer reservoir where crossflow occurs between reservoir layers. A simple algebraic expression for approximating the pseudoskin factor caused by restricted entry is presented. It is shown that, for practical purposes, this equation yields sufficiently accurate estimates of the pseudoskin factor regardless of the location of the open interval.This work also extends single-layer results of interest in well testing to the multilayer case and shows that if sufficient data are available, the results of this work can be used to prepare a complete analysis of well testing pressure data obtained at a restricted-entry well.

  7. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  8. Evolution of the antiretroviral restriction factor TRIMCyp in Old World primates.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Dietrich

    Full Text Available The retroviral restriction factor TRIMCyp, which is a fusion protein derived from the TRIM5 gene, blocks replication at a post-entry step. Among Old World primates, TRIMCyp has been found in four species of Asian macaques, but not in African monkeys. To further define the evolutionary origin of Old World TRIMCyp, we examined two species of baboons (genus Papio and three additional macaque species, including M. sylvanus, which is the only macaque species found outside Asia, and represents the earliest diverging branch of the macaque lineage. None of four P. cynocephalus anubis, one P. hamadryas, and 36 M. sylvanus had either TRIMCyp mRNA or the genetic features required for its expression. M. sylvanus genomic sequences indicated that the lack of TRIMCyp in this species was not due to genetic homogeneity among specimens studied and revealed the existence of four TRIM5α alleles, all distinct from M. mulatta and Papio counterparts. Together with existing data on macaque evolution, our findings indicate that TRIMCyp evolved in the ancestors of Asian macaques approximately 5-6 million years before present (ybp, likely as a result of a retroviral threat. TRIMCyp then became fixed in the M. nemestrina lineage after it diverged from M. nigra, approximately 2 million ybp. The macaque lineage is unique among primates studied so far due to the presence and diversity of both TRIM5 and TRIMCyp restriction factors. Studies of these antiviral proteins may provide valuable information about natural antiviral mechanisms, and give further insight into the factors that shaped the evolution of macaque species.

  9. Antagonism of tetherin restriction of HIV-1 release by Vpu involves binding and sequestration of the restriction factor in a perinuclear compartment.

    Directory of Open Access Journals (Sweden)

    Mathieu Dubé

    2010-04-01

    Full Text Available The Vpu accessory protein promotes HIV-1 release by counteracting Tetherin/BST-2, an interferon-regulated restriction factor, which retains virions at the cell-surface. Recent reports proposed beta-TrCP-dependent proteasomal and/or endo-lysosomal degradation of Tetherin as potential mechanisms by which Vpu could down-regulate Tetherin cell-surface expression and antagonize this restriction. In all of these studies, Tetherin degradation did not, however, entirely account for Vpu anti-Tetherin activity. Here, we show that Vpu can promote HIV-1 release without detectably affecting Tetherin steady-state levels or turnover, suggesting that Tetherin degradation may not be necessary and/or sufficient for Vpu anti-Tetherin activity. Even though Vpu did not enhance Tetherin internalization from the plasma membrane (PM, it did significantly slow-down the overall transport of the protein towards the cell-surface. Accordingly, Vpu expression caused a specific removal of cell-surface Tetherin and a re-localization of the residual pool of Tetherin in a perinuclear compartment that co-stained with the TGN marker TGN46 and Vpu itself. This re-localization of Tetherin was also observed with a Vpu mutant unable to recruit beta-TrCP, suggesting that this activity is taking place independently from beta-TrCP-mediated trafficking and/or degradation processes. We also show that Vpu co-immunoprecipitates with Tetherin and that this interaction involves the transmembrane domains of the two proteins. Importantly, this association was found to be critical for reducing cell-surface Tetherin expression, re-localizing the restriction factor in the TGN and promoting HIV-1 release. Overall, our results suggest that association of Vpu to Tetherin affects the outward trafficking and/or recycling of the restriction factor from the TGN and as a result promotes its sequestration away from the PM where productive HIV-1 assembly takes place. This mechanism of antagonism that results

  10. Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

    Institute of Scientific and Technical Information of China (English)

    Julie L Frey; David P Stonko; Marie-Claude Faugere; Ryan C Riddle

    2014-01-01

    The hypoxia inducible factors (Hifs) are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone (PTH). Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of b-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

  11. Evaluation of Arable Land Reserve Resources and Analysis of Restrictive Factors: A Case Study of Hangjin Banner in Inner Mongolia

    Institute of Scientific and Technical Information of China (English)

    Xia; YANG; Xiangjun; YUN

    2015-01-01

    Taking land available for cultivation and mining land available for reclamation in Hangjin Banner of Inner Mongolia Autonomous Region,using land use database of 2012 as evaluation base,it made evaluation of arability of 677 021. 40 hm2 reserve land resources by the restrictive factor evaluation method. Besides,it analyzed main restrictive factors of arable land reserve resources in Hangjin Banner. Results indicate that the total area arable land reserve resources is 52 200. 02 hm2,accounting for 7. 71% of total area evaluated. Irrigation condition and soil thickness are major factors restricting development of arable land reserve resources in the study area. It is expected to provide reference for development of arable land reserve resources and land consolidation project in Hangjin Banner.

  12. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    Science.gov (United States)

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  13. Is abnormal vaginal microflora a risk factor for intrauterine fetal growth restriction?

    Institute of Scientific and Technical Information of China (English)

    NatalijaVedmedovska; Dace Rezeberga; GilbertG G Donders

    2015-01-01

    Objective:To conduct a literature review in search of possible preventable causes for fetal growth restriction.Methods:We performed a systematic literature search regarding abnormal vaginal microflora and fetal growth encompassing the last 27-year (starting from 1986) in PubMed, Embase, and Cochrane Central to study the evidence that abnormal vaginal microflora is may be related to diminished fetal growth or small for date birth.Results:Most of the 14 studies suggested a significant role of vaginal organisms in impaired fetal growth, unrelated to preterm birth. The neonatal outcome has shown to be largely linked to the preventable or foreseeable fetal factors, such as genetic abnormalities, but also ascending intrauterine infections. Our previous work suggested a role of vaginal organisms in adverse pregnancy outcome, not only preterm birth, but also impaired fetal growth.Conclusions:There is a need for cohort studies designed to unravel this link between abnormal microflora and FGR, in order to enable preventive actions to protect these small babies from severe damage and death by early screening and treatment.

  14. Intrauterine growth restriction: distribution, risk factors, management of labour and outcome

    Directory of Open Access Journals (Sweden)

    Diana Andzane

    2015-08-01

    Full Text Available Background: The development of Intrauterine growth restriction (IUGR determines maternal, fetal and placental factors. Many of these factors are preventable. There is still no enough developed effective pregnancy and labour management tactics that could protect both mother and child from the unintended consequences. Methods: The research was made in Riga Maternity Hospital. In the research there were included pregnant women who gave birth neonates with weight under 10th percentile (IUGR group as well there was compiled the control group. The weight of neonates was evaluated using the percentile scales - Intrauterine Growth Curves based on US data. Results: According to the criteria, in the IUGR group were included 209 pregnant women and in the control group was the same number of patients. In the IUGR group mothers discharged from the hospital one day later than it was in the control group both after vaginal delivery (4.0 +/- 1.5 vs. 3.3 +/- 1.0, p and #706;0.0001 and after caesarean (5.6 +/- 1.5 vs. 4.5 +/- 1.0, p=0.0001. Comparing the evaluations after Apgar scale after spontaneous birth, induced labour and caesarean it was discovered that there is no statistically significant difference. Conclusions: IUGR negatively affect not just the fetus but also the mother and this is the reason why she should stay in the hospital for a longer period due to the child or experience the caesarean. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1117-1121

  15. Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.

    Science.gov (United States)

    Bristol, Sarah K; Woodruff, Teresa K

    2004-03-01

    Ovarian follicular development, follicle selection, and the process of ovulation remain poorly understood in most species. Throughout reproductive life, follicle fate is balanced between growth and apoptosis. These opposing forces are controlled by numerous endocrine, paracrine, and autocrine factors, including the ligands represented by the transforming growth factor beta (TGFbeta) superfamily. TGFbeta, activin, inhibin, bone morphometric protein (BMP), and growth differentiation factor 9 (GDF-9) are present in the ovary of many animals; however, no comprehensive analysis of the localization of each ligand or its receptors and intracellular signaling molecules during folliculogenesis has been done. The domestic cat is an ideal model for studying ovarian follicle dynamics due to an abundance of all follicle populations, including primordial stage, and the amount of readily available tissue following routine animal spaying. Additionally, knowledge of the factors involved in feline follicular development could make an important impact on in vitro maturation/in vitro fertilization (IVM/IVF) success for endangered feline species. Thus, the presence and position of TGFbeta superfamily members within the feline ovary have been evaluated in all stages of follicular development by immunolocalization. The cat inhibin alpha subunit protein is present in all follicle stages but increases in intensity within the mural granulosa cells in large antral follicles. The inhibin betaA and betaB subunit proteins, in addition to the activin type I (ActRIB) and activin type II receptor (ActRIIB), are produced in primordial and primary follicle granulosa cells. Additionally, inhibin betaA subunit is detected in the theca cells from secondary through large antral follicle size classes. GDF-9 is restricted to the oocyte of preantral and antral follicles, whereas the type II BMP receptor (BMP-RII) protein is predominantly localized to primordial- and primary-stage follicles. TGFbeta1, 2

  16. KAP1 is a host restriction factor that promotes HAdV E1B-55K SUMO modification

    DEFF Research Database (Denmark)

    Bürck, Carolin; Mund, Andreas; Berscheminski, Julia;

    2016-01-01

    epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism. IMPORTANCE: Here we describe a novel cellular restriction factor for Human Adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation...

  17. Local sequence targeting in the AID/APOBEC family differentially impacts retroviral restriction and antibody diversification.

    Science.gov (United States)

    Kohli, Rahul M; Maul, Robert W; Guminski, Amy F; McClure, Rhonda L; Gajula, Kiran S; Saribasak, Huseyin; McMahon, Moira A; Siliciano, Robert F; Gearhart, Patricia J; Stivers, James T

    2010-12-24

    Nucleic acid cytidine deaminases of the activation-induced deaminase (AID)/APOBEC family are critical players in active and innate immune responses, playing roles as target-directed, purposeful mutators. AID specifically deaminates the host immunoglobulin (Ig) locus to evolve antibody specificity, whereas its close relative, APOBEC3G (A3G), lethally mutates the genomes of retroviral pathogens such as HIV. Understanding the basis for the target-specific action of these enzymes is essential, as mistargeting poses significant risks, potentially promoting oncogenesis (AID) or fostering drug resistance (A3G). AID prefers to deaminate cytosine in WRC (W = A/T, R = A/G) motifs, whereas A3G favors deamination of CCC motifs. This specificity is largely dictated by a single, divergent protein loop in the enzyme family that recognizes the DNA sequence. Through grafting of this substrate-recognition loop, we have created enzyme variants of A3G and AID with altered local targeting to directly evaluate the role of sequence specificity on immune function. We find that grafted loops placed in the A3G scaffold all produced efficient restriction of HIV but that foreign loops in the AID scaffold compromised hypermutation and class switch recombination. Local targeting, therefore, appears alterable for innate defense against retroviruses by A3G but important for adaptive antibody maturation catalyzed by AID. Notably, AID targeting within the Ig locus is proportionally correlated to its in vitro ability to target WRC sequences rather than non-WRC sequences. Although other mechanisms may also contribute, our results suggest that local sequence targeting by AID/APOBEC3 enzymes represents an elegant example of co-evolution of enzyme specificity with its target DNA sequence.

  18. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

    Science.gov (United States)

    Landolfo, Santo; De Andrea, Marco; Dell’Oste, Valentina; Gugliesi, Francesca

    2016-01-01

    Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed “restriction factors” (RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus (HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell’s intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16 (IFI16) (a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and hDaxx; the latter three being the keys elements of nuclear domain 10 (ND10). IFI16 inhibits the synthesis of virus DNA by down-regulating UL54 transcription - a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65 (pUL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents. PMID:27563536

  19. Endogenous Murine BST-2/Tetherin Is Not a Major Restriction Factor of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Sarah L Londrigan

    Full Text Available BST-2 (tetherin, CD317, HM1.24 restricts virus growth by tethering enveloped viruses to the cell surface. The role of BST-2 during influenza A virus infection (IAV is controversial. Here, we assessed the capacity of endogenous BST-2 to restrict IAV in primary murine cells. IAV infection increased BST-2 surface expression by primary macrophages, but not alveolar epithelial cells (AEC. BST-2-deficient AEC and macrophages displayed no difference in susceptibility to IAV infection relative to wild type cells. Furthermore, BST-2 played little role in infectious IAV release from either AEC or macrophages. To examine BST-2 during IAV infection in vivo, we infected BST-2-deficient mice. No difference in weight loss or in viral loads in the lungs and/or nasal tissues were detected between BST-2-deficient and wild type animals. This study rules out a major role for endogenous BST-2 in modulating IAV in the mouse model of infection.

  20. Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression

    International Nuclear Information System (INIS)

    Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects. To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis. In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A. These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity

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

    Science.gov (United States)

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

    2015-12-01

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

  2. On the Restricting Factors & System Arrangements of Chinese Land Tenure Marketization

    Institute of Scientific and Technical Information of China (English)

    YU Peng-yi; ZHANG Wei-dong

    2003-01-01

    As a general rule of Economics of Development,economic growth and development require rational institution guarantee.Land Tenure.As a main institution factor in agricultural development,closely relates to the reform of Chinese agriculture.Based on the relevant theories of Economics of Institution and Economics of Development,and combined with the marketization process of Chinese Land Tenure of Property Rights,the article studied the effects of institutional factors and put forward some choices in the development of agriculture,which is of both significant and practical importance.

  3. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    International Nuclear Information System (INIS)

    To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

  4. Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

    Directory of Open Access Journals (Sweden)

    Chunjun Sheng

    2016-01-01

    Full Text Available Type 2 diabetes (T2D is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs and functional factors with long-term caloric restriction (CR. Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.

  5. Familial partial lipodystrophy, mandibuloacral dysplasia and restrictive dermopathy feature barrier-to-autointegration factor (BAF) nuclear redistribution.

    Science.gov (United States)

    Capanni, Cristina; Squarzoni, Stefano; Cenni, Vittoria; D'Apice, Maria Rosaria; Gambineri, Alessandra; Novelli, Giuseppe; Wehnert, Manfred; Pasquali, Renato; Maraldi, Nadir M; Lattanzi, Giovanna

    2012-10-01

    Prelamin A processing impairment is a common feature of a restricted group of rare genetic alterations/disorders associated with a wide range of clinical phenotypes. Changes in histone posttranslational modifications, alterations in non-histone chromatin proteins and chromatin disorganization have been specifically linked to impairment of specific, distinct prelamin A processing steps, but the molecular mechanism involved in these processes is not yet understood . In this study, we show that the accumulation of wild-type prelamin A detected in restrictive dermopathy (RD), as well as the accumulation of mutated forms of prelamin A identified in familial partial lipodystrophy (FPLD) and mandibuloacral dysplasia (MADA), affect the nuclear localization of barrier-to-autointegration factor (BAF), a protein able to link lamin A precursor to chromatin remodeling functions. Our findings, in accordance with previously described results, support the hypothesis of a prelamin A involvement in BAF nuclear recruitment and suggest BAF-prelamin A complex as a protein platform usually activated in prelamin A-accumulating diseases. Finally, we demonstrate the involvement of the inner nuclear membrane protein emerin in the proper localization of BAF-prelamin A complex.

  6. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  7. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus.

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  8. Analysis of Immunological, Viral, Genetic, and Environmental Factors That Might Be Associated with Decreased Susceptibility to HIV Infection in Serodiscordant Couples in Florianópolis, Southern Brazil.

    Science.gov (United States)

    Santos, Íris M; da Rosa, Elis A; Gräf, Tiago; Ferreira, Luiz G E; Petry, Andrea; Cavalheiro, Fernanda; Reiche, Edna M; Zanetti, Carlos R; Pinto, Aguinaldo R

    2015-11-01

    Individuals who have been exposed to human immunodeficiency virus (HIV) and have not been infected might possess natural resistance mechanisms. An understanding of the sociodemographic and immunological conditions that influence resistance to HIV is a challenge, and very little is known about the role of intrinsic antiviral factors that restrict HIV infection. The aim of this study was to analyze potential factors responsible for resistance to HIV infection in serodiscordant couples by comparing HIV-exposed seronegative individuals (HESN) to HIV-seropositive individuals treated with antiretroviral therapy (HIV-ART) along with healthy controls (HC). The results revealed one HLA-B*27 and two HLA-B*57 individuals among the HESN; a CCR5Δ32 heterozygous deletion was observed in one serodiscordant couple, while the homozygous genotype for this variant was not observed. There were no differences in the basal mRNA expression of APOBEC3G, CFLAR, TRIM5α, LEDGF/p75, BST-2, or SAMHD1 in CD4(+) T lymphocyte- and monocyte-enriched populations among the three groups, and lower HBD-3 concentrations were observed in saliva from HIV-ART compared to HESN and HC. The most prevalent HIV-1 subtype was C or C-containing recombinant forms. Six HIV-ART individuals and one HIV-ART individual were infected with the R5 HIV and X4 HIV strains, respectively. The ability to control infection or delay disease progression is probably defined by a balance between viral and host factors, and further evaluation should be performed in larger cohorts. Our data suggest that susceptibility to HIV infection varies among individuals and strengthens the multifactorial characteristics underlying the resistance mechanisms in HIV.

  9. Restrictive cardiomyopathy

    Science.gov (United States)

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy ... In a case of restrictive cardiomyopathy, the heart muscle is normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does not ...

  10. In vitro and in vivo analyses of a genetically—restricted antigen specific factor from mixed cell cultures of macrophage,T and B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    CHAURMW; LAUASK

    1990-01-01

    An immunostimulatory factor was identified to be secreted by antigen-pulsed macrophages.This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo.Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a geneticallyrestricted antigen specific factor (ASF).The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-qulsed macrophages with T lymphocytes,and then spleen cells,and finally the TNP-coated sheep red blood cells.

  11. The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection

    Science.gov (United States)

    Wang, Jing; Teng, Jade L. L.; Zhao, Dongdong; Ge, Pupu; Li, Bingxi; Woo, Patrick C. Y.; Liu, Cui Hua

    2016-01-01

    Macrophage-mediated innate immune responses play crucial roles in host defense against pathogens. Recent years have seen an explosion of host proteins that act as restriction factors blocking viral replication in infected cells. However, the essential factors restricting Mycobacterium tuberculosis (Mtb) and their regulatory roles during mycobacterial infection remain largely unknown. We previously reported that Mtb tyrosine phosphatase PtpA, a secreted effector protein required for intracellular survival of Mtb, inhibits innate immunity by co-opting the host ubiquitin system. Here, we identified a new PtpA-interacting host protein TRIM27, which is reported to possess a conserved RING domain and usually acts as an E3 ubiquitin ligase that interferes with various cellular processes. We further demonstrated that TRIM27 restricts survival of mycobacteria in macrophages by promoting innate immune responses and cell apoptosis. Interestingly, Mtb PtpA could antagonize TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27. TRIM27 probably works as a potential restriction factor for Mtb and its function is counteracted by Mtb effector proteins such as PtpA. Our study suggests a potential tuberculosis treatment via targeting of the TRIM27-PtpA interfaces. PMID:27698396

  12. Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21

    OpenAIRE

    Lees, Emma K.; Król, Elżbieta; Grant, Louise; Shearer, Kirsty; Wyse, Cathy; Moncur, Eleanor; Bykowska, Aleksandra S; Mody, Nimesh; Gettys, Thomas W.; Delibegovic, Mirela

    2014-01-01

    Methionine restriction (MR) decreases body weight and adiposity and improves glucose homeostasis in rodents. Similar to caloric restriction, MR extends lifespan, but is accompanied by increased food intake and energy expenditure. Most studies have examined MR in young animals; therefore, the aim of this study was to investigate the ability of MR to reverse age-induced obesity and insulin resistance in adult animals. Male C57BL/6J mice aged 2 and 12 months old were fed MR (0.172% methionine) o...

  13. 农村群众体育活动的制约因素发展对策%Study on Restricting Factors of Rural Mass Sports

    Institute of Scientific and Technical Information of China (English)

    高小爱; 陈巧弟

    2011-01-01

    采用问卷调查法,数理统计法等分析研究,认为制约农村群众体育活动的因素主要有:经济因素、社会因素、农民自身因素及自然环境因素。针对这些因素,提出相应的发展对策与建议。%Through using the method of literature review and mathematical statistics,this paper finds out the factors restricting the rural mass sports development including economic factors,social factors,natural factors and farmer factors.Based on existing factors

  14. Behavioural changes are a major contributing factor in the reduction of sarcopenia in caloric-restricted ageing mice

    NARCIS (Netherlands)

    Norren, van K.; Rusli, F.; Dijk, van M.; Lute, C.; Nagel, J.C.; Dijk, F.J.; Dwarkasing, J.T.; Boekschoten, M.V.; Luiking, Y.; Witkamp, R.F.; Müller, M.R.; Steegenga, W.T.

    2015-01-01

    Background - In rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age-induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of

  15. HLA-E-restricted cross-recognition of allogeneic endothelial cells by CMV-associated CD8 T cells: a potential risk factor following transplantation.

    Directory of Open Access Journals (Sweden)

    Mathilde Allard

    Full Text Available Although association between CMV infection and allograft rejection is well admitted, the precise mechanisms involved remain uncertain. Here, we report the characterization of an alloreactive HLA-E-restricted CD8 T cell population that was detected in the PBL of a kidney transplant patient after its CMV conversion. This monoclonal CD8 T cell population represents a sizable fraction in the blood (3% of PBL and is characterized by an effector-memory phenotype and the expression of multiple NK receptors. Interestingly, these unconventional T cells display HLA-E-dependent reactivity against peptides derived from the leader sequences of both various HCMV-UL40 and allogeneic classical HLA-I molecules. Consequently, while HLA-E-restricted CD8 T cells have potential to contribute to the control of CMV infection in vivo, they may also directly mediate graft rejection through recognition of peptides derived from allogeneic HLA-I molecules on graft cells. Therefore, as HLA-E expression in nonlymphoid organs is mainly restricted to endothelial cells, we investigated the reactivity of this HLA-E-restricted T cell population towards allogeneic endothelial cells. We clearly demonstrated that CMV-associated HLA-E-restricted T cells efficiently recognized and killed allogeneic endothelial cells in vitro. Moreover, our data indicate that this alloreactivity is tightly regulated by NK receptors, especially by inhibitory KIR2DL2 that strongly prevents TCR-induced activation through recognition of HLA-C molecules. Hence, a better evaluation of the role of CMV-associated HLA-E-restricted T cells in transplantation and of the impact of HLA-genotype, especially HLA-C, on their alloreactivity may determine whether they indeed represent a risk factor following organ transplantation.

  16. 甘孜州畜牧业发展的制约因素及对策%Restrictive Factors and Countermeasures of Animal Husbandry Development in Ganzi Prefecture

    Institute of Scientific and Technical Information of China (English)

    邓竹佳

    2012-01-01

    介绍了甘孜州畜牧业发展的优势,分析了其发展畜牧业的制约因素,并提出了相应的对策,以供参考。%The advantages of animal husbandry development were introduced,the restrictive factors of animal husbandry development were analyzed.Countermeasures were proposed for reference.

  17. Restricted Airspace

    Data.gov (United States)

    Federal Laboratory Consortium — Redstone Technical Test Center has restricted airspace up to 30,000 feet ASL. Airspace encompasses R-2104 (Redstone). Airspace is used extensively for airborne/UAV...

  18. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

    Directory of Open Access Journals (Sweden)

    Kroeger Cynthia M

    2012-10-01

    Full Text Available Abstract Background The ability of an intermittent fasting (IF-calorie restriction (CR regimen (with or without liquid meals to modulate adipokines in a way that is protective against coronary heart disease (CHD has yet to be tested. Objective Accordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women. Methods Subjects (n = 54 were randomized to either the IFCR-liquid (IFCR-L or IFCR-food based (IFCR-F diet for 10 weeks. Results Greater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm. Similar reductions (P Conclusion These findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

  19. Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption

    Directory of Open Access Journals (Sweden)

    Vesna Livrinova

    2015-09-01

    CONCLUSION: The presence of mutation MTHFR homozygous could increase the risk for development of IUGR and mutation of Factor V Leiden for placental abruption. Further investigations with more patients are warranted.

  20. A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development

    NARCIS (Netherlands)

    Fu, H.; Cai, J.; Clevers, H.; Fast, E.; Gray, S.; Greenberg, R.; Jain, M.K.; Ma, Q.; Qiu, M.; Rowitch, D.H.; Taylor, C.; Stiles, C.D.

    2009-01-01

    Forward genetic screens in genetically accessible invertebrate organisms such as Drosophila melanogaster have shed light on transcription factors that specify formation of neurons in the vertebrate CNS. However, invertebrate models have, to date, been uninformative with respect to genes that specify

  1. The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study.

    Directory of Open Access Journals (Sweden)

    Jyh-Ming Liou

    Full Text Available The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.The defined daily dose (DDD of antibiotics was analyzed using the Taiwan National Health Insurance (NHI research database. H. pylori strains isolated from treatment naïve (N=1395 and failure from prior eradication therapies (N=360 from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001. The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001, which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

  2. Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

    Institute of Scientific and Technical Information of China (English)

    In(ě)s Tomada; Nuno Tomada; Henrique Almeida; Delminda Neves

    2012-01-01

    The purpose of the current study was to evaluate the effect of a high-fat (HF) diet,energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF),angiopoietin (Ang) 1 and 2,and their receptors in rat corpus cavernosum (CC).Male Wistar rats were fed adlibitum with an HF diet for 8 or 16 weeks.After 8 weeks of the HF diet,a group of rats was subjected to energy restriction with or without exercise for 8 weeks.Control animals had free access to standard diet for the same period.After euthanasia,blood was collected and the penises removed for immunofluorescence assays (VEGF,VEGF receptor (VEGFR) 1 and 2,Ang1,Ang2 and Tie2) and semiquantification of VEGF,VEGFR1,VEGFR2,Ang1,Ang2,Tie2,endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting.HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels,higher systolic blood pressure and an increased atherogenic index.A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs.The Akt pathway was activated by the HF diet.Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression.These results emphasize the role of diet on vascular function regulation,demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/rie2 systems occurs before serum lipid changes and obesity onset,antedating structural atherosclerotic features.

  3. Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption

    Science.gov (United States)

    Livrinova, Vesna; Lega, Marija Hadzi; Dimcheva, Anita Hristova; Samardziski, Igor; Isjanovska, Rozalinda

    2015-01-01

    BACKGROUND: Factor V Leiden, Prothrombin and MTHFR gene mutation, could have an influence in pregnancy with adverse outcome Preeclamsia, IUGR and Placental abruption. AIM: The aim of this study is to investigate the presence of above mentioned inherited thrombophilias and its statistical significance, distribution among the complicated and normal pregnancy, and relative risk for carrier of mutation to develop preeclampsia, IUGR and placental abruption. MATERIAL AND METHODS: Prospective cohort study is implemented at University Clinic for Obstetric and Gynecology in Skopje, Republic of Macedonia. The study included 109 delivered patients: 40 with preeclapmsia, 22 with IUGR, 17 with placental abruption and 30 as control group with normal pregnancy. The amount of 3 ml venous blood has been used for detection of these point mutations using ThromboStrip -Opegen, QIAGEN kit manufactured for thrombotic risk. RESULTS: The highest frequency was found: in the group with preeclampsia 35% were MTHFR homozygous, IUGR -MTHFR heterozygous 45%, Placental abruption- 52.9% MTHFR heterozygous, and in the control group without thrombophilia 56.7%. There were combined thrombophilia in 3 patients. There aren`t statistical significance in presence of thrombophilia among groups (p > 0.05). Statistical significance (p < 0.05) was found between carriers of MTHFR homozygous in preeclampsia and group with placental abruption and control group. Relative risk in IUGR group for MTHFR homozygous was 5.54 (1.37Factor V Leiden heterozygous was 4.50 (0.47Factor V Leiden for placental abruption. Further investigations with more patients are warranted. PMID:27275292

  4. The critical role of personality and organizational factors as determinants of reactions to restricted and stressful environments. [undersea habitats

    Science.gov (United States)

    Helmreich, Robert L.

    1987-01-01

    Research into the impact of personality factors on groups in various settings is reviewed as an introduction to a brief discussion of personality and group behavior research needs relevant to the space program. Significant findings of some earlier research are summarized, and methodological problems are touched on. The study of intergroup and intragroup conflict in a stressful environment, as exemplified particularly by undersea habitats, is seen as being of consequence for long-term space missions. It is concluded that adequate research can only be conducted as an adjunct to data collection from operational stressful environments, and not from laboratory experiments.

  5. Hepatic insulin-like growth-factor binding protein (igfbp) responses tofood restriction in Atlantic salmon smolts

    Science.gov (United States)

    Breves, Jason P.; Phipps-Costin, Silas K.; Fujimoto, Chelsea K.; Einarsdottir, Ingibjörg E.; Regish, Amy M.; Björnsson, Björn Thrandur; McCormick, Stephen

    2016-01-01

    The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon ( Salmo salar ). Fish were fasted for 3 or 10 days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3 days and condition factor by 10 days. Plasma Gh, cortisol, and thyroxine (T 4 ) were not altered in response to fasting, whereas Igf1 and 3,5,3′-triiodo- l -thyronine (T 3 ) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1 , - 1b2 , - 2a , - 2b1 and - 2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10 days of fasting. Fasting did not alter hepatic igf1or igf2 ; however, muscle igf1 was diminished by 10 days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na + /K + -ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism.

  6. Hepatic insulin-like growth-factor binding protein (igfbp) responses to food restriction in Atlantic salmon smolts.

    Science.gov (United States)

    Breves, Jason P; Phipps-Costin, Silas K; Fujimoto, Chelsea K; Einarsdottir, Ingibjörg E; Regish, Amy M; Björnsson, Björn Thrandur; McCormick, Stephen D

    2016-07-01

    The growth hormone (Gh)/insulin-like growth-factor (Igf) system plays a central role in the regulation of growth in fishes. However, the roles of Igf binding proteins (Igfbps) in coordinating responses to food availability are unresolved, especially in anadromous fishes preparing for seaward migration. We assayed plasma Gh, Igf1, thyroid hormones and cortisol along with igfbp mRNA levels in fasted and fed Atlantic salmon (Salmo salar). Fish were fasted for 3 or 10days near the peak of smoltification (late April to early May). Fasting reduced plasma glucose by 3days and condition factor by 10days. Plasma Gh, cortisol, and thyroxine (T4) were not altered in response to fasting, whereas Igf1 and 3,5,3'-triiodo-l-thyronine (T3) were slightly higher and lower than controls, respectively. Hepatic igfbp1b1, -1b2, -2a, -2b1 and -2b2 mRNA levels were not responsive to fasting, but there were marked increases in igfbp1a1 following 3 and 10days of fasting. Fasting did not alter hepatic igf1 or igf2; however, muscle igf1 was diminished by 10days of fasting. There were no signs that fasting compromised branchial ionoregulatory functions, as indicated by unchanged Na(+)/K(+)-ATPase activity and ion pump/transporter mRNA levels. We conclude that dynamic hepatic igfbp1a1 and muscle igf1 expression participate in the modulation of Gh/Igf signaling in smolts undergoing catabolism. PMID:27210270

  7. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone

    DEFF Research Database (Denmark)

    Rasmussen, M H; Frystyk, Jan; Andersen, T;

    1994-01-01

    The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2......, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated...... = .02) weeks of dietary treatment. Both serum IGF-1 and insulin levels were positively correlated with serum IGFBP-3 levels (r = .34, P = .009 and r = .34, P = .008, respectively). We conclude that IGF-1 levels in obese females reflect the intraabdominal fat mass rather than obesity per se. IGF-1...

  8. Study on the Factors Restricting the Development of Rural Specialized Cooperatives%农村专业合作社发展制约因素研究

    Institute of Scientific and Technical Information of China (English)

    张建宁

    2012-01-01

    As an organization carrier of new rural economic order, the rural specialized cooperatives could not only promote the development of rural economic, but could also play a positive role in standardization of rural social management. Factors restricting the development of rural specialized cooperatives were analyzed; and suggestions were proposed accordingly, which could help improving and solving problems of agriculture, rural areas and farmers.%农村专业合作社作为农村经济新秩序中的一个组织载体,不仅能推动农村经济的繁荣发展,而且对农村的社会管理也有规范作用.分析制约农村专业合作社发展的因素,提出建议,对改进并解决“三农”问题具有现实意义.

  9. Main Restrictive Factors and Countermeasures of Rice Industry in China%中国水稻生产制约因素及发展对策

    Institute of Scientific and Technical Information of China (English)

    杨红旗; 郝仰坤

    2011-01-01

    The situations of new Chinese rice breeding progress and production history were reviewed briefly in the paper.Though Chinese rice breeding has reached advanced levels in the world for years, and great achievements have been made in rice production, there are some restrictive factors to be studied and solved conscientiously.The restrictive factors including the shortage of agricultural resources, the lack of dominant varieties, the low level of mechanization, etc.were analyzed, some appropriate countermeasures such as scientific utilization of agricultural resources, optimization of varieties and regional distribution, promotion of mechanization and so on were put forward, and the way of future development was also pointed out to promote more healthy and orderly rice industry development.%简要回顾了新中国水稻育种进展和生产发展历程,指出尽管水稻育种数十年保持国际领先水平,水稻生产取得了辉煌的发展成就,但仍然存在一些制约因素亟待认真研究解决.在剖析农业资源紧缺、突破性品种缺乏、机械化作业水平较低等发展制约因素的基础上,对中国水稻生产提出了科学利用农业资源、优化品种与区域布局、促进机械化发展等对策建议,并指明了中国水稻生产未来发展方向,旨在促进中国水稻产业更加健康有序发展.

  10. Calorie restriction and stroke

    Directory of Open Access Journals (Sweden)

    Manzanero Silvia

    2011-09-01

    Full Text Available Abstract Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR or intermittent fasting (IF, extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF and basic fibroblast growth factor (bFGF; protein chaperones, including heat shock protein 70 (Hsp70 and glucose regulated protein 78 (GRP78; antioxidant enzymes, such as superoxide dismutases (SOD and heme oxygenase-1 (HO-1, silent information regulator T1 (SIRT1, uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke.

  11. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. PMID:25691247

  12. Detection of Polymorphism at the Insulin Like Growth Factor-I Gene in Mazandaran Native Chicken using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Method

    Directory of Open Access Journals (Sweden)

    Hossein A. Abbasi

    2011-01-01

    Full Text Available Problem statement: Molecular genetics selection on individual genes is a promising method to genetically improve economically important traits in chickens. The Insulin like Growth Factor-I (IGF1 gene may play important roles in growth of multiple tissues, including muscle cells, cartilage and bone. Approach: In the present study polymorphism of the promoter and 5' untranslated region of IGF-1 gene of Mazandaran native fowls was investigated. In order to evaluate the IGF-1 gene polymorphism we have used a Restriction Fragment Length Polymorphism (RFLP method. Blood samples were collected from randomly chosen 100 Mazandaran native fowls. Genomic DNA was extracted using modified salting-out method and used amplified polymerase chain reaction technique. The promoter and 5' untranslated region of the fowl IGF-1 gene was amplified to produce a 621 bp fragment. The PCR products were electrophoresed on 2.5% agarose gel and stained by etidium bromide. Results: Then, they were digested of amplicon with PstI and revealed two alleles A and B. Data were analyzed using Pop Gene 32 package. In this population, AA, AB, BB genotype have been identified with the 25.88, 50.23, 23.89% frequencies. A and B alleles frequencies were 0.51, 0.49, respectively. The Chi-square (÷2 test was significant and the population was in Hardy-Weinberg equilibrium (pConclusion: The PCR technique amplified a DNA fragment of IGF-1 with 621 bp. The results of the RFLP analysis showed two fragment 257 and 354bp after restriction with enzyme with PstI that identify changes in 5' untranslated region. In according to action modes and importance of IGF-1, its polymorphisms can be related to economical traits such as body weight, muscle cells and bone.

  13. Evaluation of udder health parameters and risk factors for clinical mastitis in Dutch dairy herds in the context of a restricted antimicrobial usage policy.

    Science.gov (United States)

    Santman-Berends, I M G A; Swinkels, J M; Lam, T J G M; Keurentjes, J; van Schaik, G

    2016-04-01

    study indicated that udder health had not deteriorated compared with udder health in previous Dutch studies where herd sizes were somewhat smaller and before the restrictions in antimicrobial use. Several of the risk factors that were found can be influenced by the farmer and can prevent the occurrence of CMI. Still, when cases of CM occur, treatment with antimicrobials might be necessary to cure the CM case and is beneficial for the overall udder health in the herd. PMID:26874413

  14. Improved restriction landmark cDNA scanning and its application to global analysis of genes regulated by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Mayumi, K; Yaoi, T; Kawai, J; Kojima, S; Watanabe, S; Suzuki, H

    1998-07-30

    Restriction landmark cDNA scanning (RLCS) is a novel method by which more than 1000 genes can be simultaneously and quantitatively displayed as two-dimensional gel spots. Here we present an adaptation that allows an individual spot to correspond to a unique gene species without redundancy in more than two gel patterns. Using this improved RLCS, we examined global changes on the gene expression of PC12 cells before and after treatment with nerve growth factor. Among a total of 3000 spots, 21 (0.70%) and 91 (3.03%) spots newly appeared and became more intense with treatment. On the other hand, 15 (0.50%) and 44 (1.47%) spots disappeared, becoming less intense with treatment. These observations suggest that approx. 6% of the detected PC12 genes are up-(3.73%) or down-(1.97%) regulated when the cells differentiate to neuronal cells. In comparison with the results obtained using the expressed-sequence-tag approach, previously reported by Lee et al. (Proc. Natl. Acad. Sci. USA 92 (1995) 8303-8307), RLCS should be useful for quantitatively examining the global change of differentially expressed genes of various expression levels. PMID:9714711

  15. The effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia

    NARCIS (Netherlands)

    Faassen, A. van; Ploeg, E.M.C. van der; Habets, H.M.L.; Meer, R. van der; Hermus, R.J.J.; Janknegt, R.A.

    1998-01-01

    The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-r

  16. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

    Directory of Open Access Journals (Sweden)

    Kelly M Cheney

    Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

  17. Effects of calorie restriction and diet-induced obesity on murine colon carcinogenesis, growth and inflammatory factors, and microRNA expression.

    Directory of Open Access Journals (Sweden)

    Susan E Olivo-Marston

    Full Text Available Obesity is an established colon cancer risk factor, while preventing or reversing obesity via a calorie restriction (CR diet regimen decreases colon cancer risk. Unfortunately, the biological mechanisms underlying these associations are poorly understood, hampering development of mechanism-based approaches for preventing obesity-related colon cancer. We tested the hypotheses that diet-induced obesity (DIO would increase (and CR would decrease colon tumorigenesis in the mouse azoxymethane (AOM model. In addition, we established that changes in inflammatory cytokines, growth factors, and microRNAs are associated with these energy balance-colon cancer links, and thus represent mechanism-based targets for colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and randomized to: 1 control diet; 2 30% CR diet; or 3 DIO diet. Mice were euthanized at week 5 (n = 12/group, 10 (n = 12/group, and 20 (n = 20/group after the last AOM injection. Colon tumors were counted, and cytokines, insulin-like growth factor 1 (IGF-1, IGF binding protein 3 (IGFBP-3, adipokines, proliferation, apoptosis, and expression of microRNAs (miRs were measured. The DIO diet regimen induced an obese phenotype (∼36% body fat, while CR induced a lean phenotype (∼14% body fat; controls were intermediate (∼26% body fat. Relative to controls, DIO increased (and CR decreased the number of colon tumors (p = 0.01, cytokines (p<0.001, IGF-1 (p = 0.01, and proliferation (p<0.001. DIO decreased (and CR increased IGFBP-3 and apoptosis (p<0.001. miRs including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and mir-138 were differentially expressed between the dietary groups. We conclude that the enhancing effects of DIO and suppressive effects of CR on colon carcinogenesis are associated with alterations in several biological pathways, including inflammation, IGF-1, and microRNAs.

  18. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    Science.gov (United States)

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR. PMID:25010399

  19. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  20. Achieving Salt Restriction in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Emma J. McMahon

    2012-01-01

    Full Text Available There is consistent evidence linking excessive dietary sodium intake to risk factors for cardiovascular disease and chronic kidney disease (CKD progression in CKD patients; however, additional research is needed. In research trials and clinical practice, implementing and monitoring sodium intake present significant challenges. Epidemiological studies have shown that sodium intake remains high, and intervention studies have reported varied success with participant adherence to a sodium-restricted diet. Examining barriers to sodium restriction, as well as factors that predict adherence to a low sodium diet, can aid researchers and clinicians in implementing a sodium-restricted diet. In this paper, we critically review methods for measuring sodium intake with a specific focus on CKD patients, appraise dietary adherence, and factors that have optimized sodium restriction in key research trials and discuss barriers to sodium restriction and factors that must be considered when recommending a sodium-restricted diet.

  1. 我国扩大消费的制约因素及对策研究%Research on the restricting factors and countermeasures of expanding spending power

    Institute of Scientific and Technical Information of China (English)

    张磊

    2012-01-01

    随着经济社会的进一步发展,传统经济发展模式的弊端逐渐显露出来。要克服传统经济发展模式的弊端,需要转变经济发展方式,建立以消费为主导,消费、投资和出口协调拉动的经济发展模式。通过论述经济与社会发展之间的关系,探讨制约我国扩大消费实践中存在的制约因素,并针对这些影响因素提出合理的政策建议。首先,论证建立以消费为主导的发展模式,是实现经济社会可持续发展的必由之路;其次,分别分析现行分配制度、经济发展模式和供给结构对扩大消费的制约作用;最后,将扩大消费的对策放在限制政府对市场的干预行为,提高居民的收入水平、完善消费品供给结构、提高农民收入、健全基本公共服务体系、稳定物价等6个方面。%With the development of economy and community, the traditional economic growth mode reveals its disadvantages. The proportion of consumption must be increased to get over the difficulty. This article looks for the restraining factors which hinder the expansion of consumption by analyzing the relationship between the economic and social development. First, we can arrive at conclusion from the analysis that it is the only way of social and economic sustainable develop- ment to establish consumption for the leading model of development; Second, the paper analyzes consumption restriction role of the distribution system, the model of economic development and the supply structure. Third, the article focuses the points of application on limiting the govern- ment to market intervention behavior;raising the income level of resident;perfecting goods supply structure;improving farmers' income;constructing basic public service system and stabilizing com- modity prices.

  2. Measuring the Restrictiveness of Living Environments for Children and Youth: Reconceptualizing Restriction

    Science.gov (United States)

    Rauktis, Mary E.; Huefner, Jonathan C.; O'Brien, Kirk; Pecora, Peter J.; Doucette, Ann; Thompson, Ronald W.

    2009-01-01

    The "Restrictiveness of Living Environment Scale" has long been the primary way to conceptualize the "restrictiveness" of a child's living situation. However, changes in systems of care and other factors have created a need to revisit how restrictiveness is conceptualized and measured. A measure was created to assess an environment's level of…

  3. Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2013-09-03

    Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

  4. Massively parallel characterization of restriction endonucleases

    OpenAIRE

    Kamps-Hughes, Nick; Quimby, Aine; Zhu, Zhenyu; Johnson, Eric A.

    2013-01-01

    Restriction endonucleases are highly specific in recognizing the particular DNA sequence they act on. However, their activity is affected by sequence context, enzyme concentration and buffer composition. Changes in these factors may lead to either ineffective cleavage at the cognate restriction site or relaxed specificity allowing cleavage of degenerate ‘star’ sites. Additionally, uncharacterized restriction endonucleases and engineered variants present novel activities. Traditionally, restri...

  5. Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

    International Nuclear Information System (INIS)

    The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

  6. SAMHD1, the Aicardi-Goutières syndrome gene and retroviral restriction factor, is a phosphorolytic ribonuclease rather than a hydrolytic ribonuclease.

    Science.gov (United States)

    Ryoo, Jeongmin; Hwang, Sung-Yeon; Choi, Jongsu; Oh, Changhoon; Ahn, Kwangseog

    2016-09-01

    SAMHD1 plays diverse roles in innate immunity, autoimmune diseases and HIV restriction, but the mechanisms involved are still unclear. SAMHD1 has been reported to have both dNTPase and RNase activities. However, whether SAMHD1 possesses RNase activity remains highly controversial. Here, we found that, unlike conventional hydrolytic exoribonucleases, SAMHD1 requires inorganic phosphate to degrade RNA substrates and produces nucleotide diphosphates rather than nucleoside monophosphates, which indicated that SAMHD1 is a phosphorolytic but not hydrolytic 3'-5' exoribonuclease. Furthermore, SAMHD1 preferentially cleaved single-stranded RNAs comprising A20 or U20, whereas neither C20 nor G20 was susceptible to SAMHD1-mediated degradation. Our findings will facilitate more advanced studies into the role of the SAMHD1 RNase function in the cellular pathogenesis implicated in nucleic acid-triggered inflammatory responses and the anti-retroviral function of SAMHD1. PMID:27387229

  7. Investigation Analysis of the City Inhabitants Participate Community Sports Motivation and Its Restrictive Factors%城市居民参加社区体育动机及其制约因素的调查分析

    Institute of Scientific and Technical Information of China (English)

    葛冰

    2012-01-01

    Take the Jilin Province partial city community inhabitants as the sample,investigate the motivation and the restrictive factors from the questionnaire that city inhabitants participates in the community sports,using the mathematical statistic method,discussion the difference of the motivation and the restrictive factors that community inhabitants participates in community sports.Result show:24.1% city inhabitants participate in community sports above 3 time/week;The first three motivation that inhabitants participates in the community sports is the enhance physical,the leisure and entertainment,the fitness and loses weight;The restriction factors existence significant differences that the city inhabitants participate in community sports in physiology,psychology,facilities,society and so on.%以吉林省部分城市社区居民为样本,对城市居民参加社区体育动机及其制约因素进行问卷调查,运用数理统计方法探讨城市居民参加社区体育动机和制约因素的差异。结果显示:有24.1%的城市居民参加3次/周以上的社区体育活动;参加社区体育动机前三位的是增强体质、休闲娱乐、健美减肥;城市居民参加社区体育的制约因素在生理、心理、设施和社会等层面存在显著差异。

  8. Restricting retrotransposons: a review.

    Science.gov (United States)

    Goodier, John L

    2016-01-01

    Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic "parasites", focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation. Some factors act in the nucleus and involve DNA repair enzymes or epigenetic processes of DNA methylation and histone modification. RISC and piRNA pathway proteins protect the germline. Retrotransposon control is relaxed in some cell types, such as neurons in the brain, stem cells, and in certain types of disease and cancer, with implications for human health and disease. This review also considers potential pitfalls in interpreting retrotransposon-related data, as well as issues to consider for future research. PMID:27525044

  9. An Analysis on Institutional Restriction Factor of Financial Holding Company Development in China%我国金融控股公司发展的制度性制约因素分析

    Institute of Scientific and Technical Information of China (English)

    成娜

    2012-01-01

    我国没有专门的金融控股公司法,但是事实上存在各种类型的金融控股公司。制约金融控股股公司的发展的因素除法律因素外,还包括公司转投资限制、母公司融资限制和税收制度限制等。在分业监管体制下.我国金融控股公司立法很难有实质性突破,研究分析专门立法之外的因素更具有现实意义。%There is no special law on financial holding companies, but in fact there exist many kinds of financial holding compa- nies. Apart from legal factor, restrictions on company investment transfer, parent company financing and taxation system all restrict the development of financial holding companies. Under the separated supervision flame, making a law on financial holding companies is hard to make a material progress. Therefore, it is meaningful to study and analyze other factors beyond legal factor.

  10. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration

    OpenAIRE

    Chujo, Yoshikazu; Fujii, Namiki; Okita, Naoyuki; Konishi, Tomokazu; Narita, Takumi; Yamada, Atsushi; Haruyama, Yushi; Tashiro, Kosuke; Chiba, Takuya; Shimokawa, Isao; Higami, Yoshikazu

    2012-01-01

    The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adipose tissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6–7-month-old wild-type Wistar rats fed ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although ...

  11. Change in prevalence of restrictive lung impairment in the U.S. population and associated risk factors: the National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 2007–2010

    OpenAIRE

    Kurth, Laura; Hnizdo, Eva

    2015-01-01

    Background Data for the U.S adult population from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate risk factors for a restrictive pattern on spirometry and estimate the change in its prevalence from the 1988–1994 to 2007–2010 sampling periods. Several previous epidemiologic studies used the Global Initiative for Chronic Obstructive Lung Disease fixed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70 criteria for classifying restr...

  12. Estimating Trade Restrictiveness Indices

    OpenAIRE

    Kee, Hiau Looi; Nicita, Alessandro; Olarreaga, Marcelo

    2009-01-01

    Studies of the impact of trade restrictiveness on growth, poverty, or unemployment are frequent in the academic literature. Few authors, however, provide a precise definition of what they mean by trade restrictiveness. When they do, the definition is unlikely to have tight links with trade theory. The objective of this article is to fill this gap by providing for 78 developing and developed countries clearly defined indicators of trade restrictiveness that are well grounded in trade theory. R...

  13. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    The article discusses three central aspects of the freedoms under European Community law, namely 1) the prohibition against restrictions as an important extension of the prohibition against discrimination, 2) a prohibition against exit restrictions which is just as important as the prohibition...... against host country restrictions, but which is often not recognised to the same extent by national law, and 3) the importance of also identifying and recognising an exit restriction, so that it is possible to achieve the required test of appropriateness and proportionality in relation to the rule...

  14. Effect of Vitamin D Receptor Gene Foki Restriction Sites and Gastric Factors%维生素D受体基因FokI酶切位点与胃癌的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    方法; 高洁; 王海江

    2016-01-01

    目的:探讨维生素D受体基因 Fok I酶切位点多态性与胃癌的影响因素。方法随机选取2013年5月—2015年5月该院就诊的维吾尔族胃癌患者143例(A组)及维吾尔族健康对照者147例(B组),采用多聚酶链反应-限制性酶切片段长度多态性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)方法测定维生素D受体基因Fok I酶切位点多态性,进行两组间比较。结果单因素Logistic回归分析显示:胃癌患者的f等位基因频率高于对照组(58.0%vs 47.3%,P<0.05)。多因素Logistic回归分析显示:带有f等位基因(Ff+ ff)的受试者表现出较高的患胃癌的风险(OR值2.87)。结论 VDR的FokI酶切位点多态性是胃癌易感性影响因素。 f等位基因可能是胃癌发生的危险因素之一,而F等位基因可能是胃癌的保护因素。%Objective Discussion of vitamin D receptor gene Fok I restriction site polymorphism influencing factors and gastric cancer. Methods 143 cases of Uygur patients with gastric cancer treated in our hospital from May 2013 to May 2015 were randomly selected as the group A, 147 cases of Uygur healthy people treated in our hospital at the same period were selected as the group B (control group ), the polymorphism of vitamin D acceptor gene FokI restriction enzyme cutting site was measured by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method,PCR-RFLP and com-pared between the two groups. Results The single factor Logistic regression analysis showed that F allele frequency in the gastric cancer group was higher than that in the control group (58.0% vs 47.3%,P<0.05), multi-factor Logistic regression analysis showed that the subjects with F allele(Ff + ff)had a higher risk of gastric cancer(OR value was 2.87). Conclusion VDR FokI restriction site polymorphisms are susceptibility factors in gastric cancer. F allele may be one of the risk factors of occurrence of gastric cancer, however, F allele

  15. CD8+-Cell Antiviral Factor Activity Is Not Restricted to Human Immunodeficiency Virus (HIV)-Specific T Cells and Can Block HIV Replication after Initiation of Reverse Transcription

    OpenAIRE

    Le Borgne, Sylvie; Février, Michèle; Callebaut, Christian; Lee, Steven P.; Rivière, Yves

    2000-01-01

    CD8+ lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4+ T cells by a noncytolytic mechanism involving secreted CD8+-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4+ T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector pha...

  16. RhoJ is an endothelial cell-restricted Rho GTPase that mediates vascular morphogenesis and is regulated by the transcription factor ERG

    NARCIS (Netherlands)

    Yuan, Lei; Sacharidou, Anastasia; Stratman, Amber N.; Le Bras, Alexandra; Zwiers, Peter J.; Spokes, Katherine; Bhasin, Manoj; Shih, Shou-ching; Nagy, Janice A.; Molema, Grietje; Aird, William C.; Davis, George E.; Oettgen, Peter

    2011-01-01

    ERG is a member of the ETS transcription factor family that is highly enriched in endothelial cells (ECs). To further define the role of ERG in regulating EC function, we evaluated the effect of ERG knockdown on EC lumen formation in 3D collagen matrices. Blockade of ERG using siRNA completely inter

  17. Alphavirus Restriction by IFITM Proteins.

    Science.gov (United States)

    Weston, Stuart; Czieso, Stephanie; White, Ian J; Smith, Sarah E; Wash, Rachael S; Diaz-Soria, Carmen; Kellam, Paul; Marsh, Mark

    2016-09-01

    Interferon inducible transmembrane proteins (IFITMs) are broad-spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by either virus. IFITM3 inhibits release of the SFV capsid into the cytosol, without inhibiting binding, internalization, trafficking to endosomes or low pH-induced conformational changes in the envelope glycoprotein. Infection by SFV fusion at the cell surface was inhibited by IFITM1, but was equally inhibited by IFITM3. Furthermore, an IFITM3 mutant (Y20A) that is localized to the plasma membrane inhibited infection by cell surface fusion more potently than IFITM1. Together, these results indicate that IFITMs, in particular IFITM3, can restrict alphavirus infection by inhibiting viral fusion with cellular membranes. That IFITM3 can restrict SFV infection by fusion at the cell surface equivalently to IFITM1 suggests that IFITM3 has greater antiviral potency against SFV. PMID:27219333

  18. 中国竞技排球发展制约因素的研究%Study on the Restrictive Factors of the Development of the Chinese Competitive Volleyball

    Institute of Scientific and Technical Information of China (English)

    古松; 钟秉枢

    2012-01-01

    By the method of questionnaire and factor analysis,the research takes the research objects of the officials of China Volleyball Management Center,volleyball scholar,national team coaches,coaches of men's and women's volleyball clubs participating in the National Volleyball League,international and national volleyball referees.Major restrictive factors in the development on the Chinese competitive volleyball have been researched and analyzed.The result shows that current major factors restricting the development of Chinese competitive volleyball are: management models,athletes' culture quality,volleyball club,training effect,the effect of reserve training and coaches.%采用问卷调查、因子分析法以中国排球管理中心相关领导,排球学者,国家队教练员,参加全国排球甲A联赛的各俱乐部男女排教练员和国际、国家级排球裁判员等为调查对象,对当前中国竞技排球发展过程中的主要制约因素进行研究并对各因素进行分析。结果显示,当前制约中国竞技排球发展的主要因素有:管理模式、运动员文化素质、排球俱乐部、训练影响、后备培养和教练员影响。

  19. Psychological factors in analogous thinking and their restriction%类比思维的心理因素及其制约

    Institute of Scientific and Technical Information of China (English)

    张晓芒

    2006-01-01

    AIM: To investigate the role of certain psychological factors in the process of new analogous combination on the basis of complete perceptual materials.METHODS: By means of evaluation of critical thinking, the psychological factors in the process of analogous thinking were investigated.RESULTS: In the process of analogous thinking, how to choose and reflect the analogous objects has its proper use of analogous mode of thinking. At the same time, it is also influenced by certain psychological factors.CONCLUSION: Analogous thinking plays an important role as thinking tool in the process of recognizing new things and solving new problems, or explaining abstract affair with simple reasons.%目的:探讨一定的心理因素在完整的知觉材料基础上进行新的类比组合过程中的作用.方法:以批判性思维的评价方法,对类比思维过程中心理因素进行研究.结果:在类比思维的过程中,如何选择、映射类比事物,不但有着正确的类比思维方法的运用,同时它也受到一定的心理因素的影响.结论:类比思维在认识新事物、解决新问题的过程中,或者以简单的道理说明抽象事理的过程中,都发挥着重要的思维工具作用.

  20. Change in proportional protein intake in a 10-week energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors

    DEFF Research Database (Denmark)

    Stocks, Tanja; Taylor, Moira A; Ängquist, Lars;

    2013-01-01

    Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal e...... increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet. Copyright © 2013 S. Karger GmbH, Freiburg.......Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal...... energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (2) on outcomes...

  1. Restrictions of stable bundles

    CERN Document Server

    Balaji, V

    2011-01-01

    The Mehta-Ramanathan theorem ensures that the restriction of a stable vector bundle to a sufficiently high degree complete intersection curve is again stable. We improve the bounds for the "sufficiently high degree" and propose a possibly optimal conjecture.

  2. The Affecting Factors to Restrict Increasing Convert Ratio of Fluid Catalytic Cracking Unit%制约提高催化裂化转化率的影响因素分析

    Institute of Scientific and Technical Information of China (English)

    曹小伟

    2012-01-01

    通过运用催化裂化相关理论并结合惠州炼油分公司催化裂化装置的实际生产情况,对影响催化裂化转化率的因素进行了分析,通过分析各操作参数间的相互关系,确定在装置掺炼加氢尾油后,油浆系统是制约提高转化率的关键因素。%On the basis of the fluid catalytic cracking theory,the main process parameters of FCC unit in Huizhou Oil Refining Company were analyzed,that the slurry oil system was the important restrict factor to increase the convert ratio when FCC unit process the feed mixed with hydro-cracking unconverted oil.

  3. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-01-01

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated. PMID:26986509

  4. Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology.

    Science.gov (United States)

    Hu, C; Cao, H; Pan, X; Li, J; He, J; Pan, Q; Xin, J; Yu, X; Li, J; Wang, Y; Zhu, D; Li, L

    2016-01-01

    Current evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated. PMID:26986509

  5. Methionine restriction and life-span control.

    Science.gov (United States)

    Lee, Byung Cheon; Kaya, Alaattin; Gladyshev, Vadim N

    2016-01-01

    Dietary restriction (DR) without malnutrition is associated with longevity in various organisms. However, it has also been shown that reduced calorie intake is often ineffective in extending life span. Selecting optimal dietary regimens for DR studies is complicated, as the same regimen may lead to different outcomes depending on genotype and environmental factors. Recent studies suggested that interventions such as moderate protein restriction with or without adequate nutrition (e.g., particular amino acids or carbohydrates) may have additional beneficial effects mediated by certain metabolic and hormonal factors implicated in the biology of aging, regardless of total calorie intake. In particular, it was shown that restriction of a single amino acid, methionine, can mimic the effects of DR and extend life span in various model organisms. We discuss the beneficial effects of a methionine-restricted diet, the molecular pathways involved, and the use of this regimen in longevity interventions.

  6. Social Factors of Restricting Chinese to Renew Eyesight by Cataract Operations%制约国人白内障复明手术的社会因素

    Institute of Scientific and Technical Information of China (English)

    傅波; 安海鸥; 冯万国; 孙璐

    2011-01-01

    There is about 20 million people lost their vision just because of cataract, and the number of low vision by cataract is three times more than that gets to 60 million. Cataract surgery can restore normal or some useful vision. It is an effective measure of eye care scale in the different environment that the number of cataract operations (cataract surgery rate)is calculated in per million people every year. There is big significant different rate of cataract between different countries or in different regions. The highest rate is 16,000 cases/million in Belgium. In our country, there are 448.7 cases/million base upon statistics in 2004. Aceording to the policy which made by Ministry of Health of China, the rate of cataract surgery will reach to 700 cases/million in the next 5 years, 2006-2010. This difference is constrained by the host country and the patient's own economic and cultural degrees and other social factors, even if it has surgery services. It is difficult to be useful. This paper reviewed retrospectively on prevention of blindness in 20 years, Liaoning Province and Dalian City, discussing the cataract operations from the constraints of social factors.%全球因白内障致失明者大约2 000万人,导致低视力者3倍于此数字,即6 000万.手术可使白内障失明者视力恢复正常或有用视力.每年每百万人口接受白内障手术的人数(白内障手术率)是在不同环境中衡量眼保健工作的有用尺度.白内障手术率在各国之间以及一个国家的不同地区都存在极大差异,最高者比利时16 000例/百万,2004年统计我国448.7例/百万,2005卫生部制定的2006~2010全国今后5年白内障手术率要达到700例/百万.这种差异是受所在国和地区及患者本人的经济和文化程度及其他社会因素所制约的,即使具备手术服务也很难予以利用.本文拟就防盲治盲20年间,辽宁省及大连市白内障复明手术开展情况进行回顾性分析,从制约国人

  7. Neuroaesthetics: range and restrictions.

    Science.gov (United States)

    Chatterjee, Anjan

    2013-04-01

    Bullot & Reber (B&R) should be commended for highlighting tensions between scientific aesthetics and art history. The question of how each tradition can learn from the other is timely. While I am sympathetic to their views, their diagnosis of the problem appears exaggerated and their solution partial. They underestimate the reach of scientific aesthetics while failing to identify its inherent restrictions. PMID:23507092

  8. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...

  9. Bilinear Fourier restriction theorems

    CERN Document Server

    Demeter, Ciprian

    2012-01-01

    We provide a general scheme for proving $L^p$ estimates for certain bilinear Fourier restrictions outside the locally $L^2$ setting. As an application, we show how such estimates follow for the lacunary polygon. In contrast with prior approaches, our argument avoids any use of the Rubio de Francia Littlewood--Paley inequality.

  10. Analysis of Risk Factors for Fetal Growth Restriction and Delivery Timing%胎儿生长受限危险因素及分娩时机的分析

    Institute of Scientific and Technical Information of China (English)

    崔世红; 孙俊燕; 陈娟; 李园园; 杭中霞; 申琳娜; 职云晓; 高亚南

    2015-01-01

    Objective:To explore the related risk factors for fetal growth restriction and time to termination of pregnancy.Method:The clinical data of 173 neonates with FGR(FGR group),180 neonates with normal weight(normal group) and the parturient women in the Third Affiliated Hospital of Zhengzhou University were selected from January 2013 to November 2014,they were analyzed retrospectively.Result:The high risk factors of fetal growth restriction were: gestational hypertension disease (P=0.000,OR=20.440,95%CI 8.499-49.156),oligohydramnios(P=0.000, OR=5.652,95%CI 2.195-14.555),gestational diabetes(P=0.018,OR=2.763,95%CI 1.192-6.400) and anemia (P=0.032,OR=1.708,95%CI 1.047-2.786).With the gestational age greater, the weight of the newborn was higher, the prognosis was better,the differences were statistically significant(P<0.05).Conclusion:Gestational hypertension disease, oligohydramnios, gestational diabetes and anemia are high risk factors of fetal growth restriction.To strengthen pregnancy care and custody,the standard treatment of obstetric complications, timely termination of pregnancy is main measures to reduce perinatal mortality.%目的:探讨胎儿生长受限的相关危险因素及终止妊娠时机。方法:对2013年1月-2014年11月在郑州大学第三附属医院分娩的173例FGR新生儿(FGR组)及180例正常体重新生儿(对照组)及其产妇病历资料进行回顾性分析。结果:胎儿生长受限的高危因素有:妊娠期高血压疾病(P=0.000,OR=20.440,95%CI 8.499~49.156)、羊水过少(P=0.000,OR=5.652,95%CI 2.195~14.555)、妊娠期糖尿病(P=0.018, OR=2.763,95%CI 1.192~6.400)和贫血(P=0.032,OR=1.708,95%CI 1.047~2.786)。孕周越大,新生儿体重越重,预后越好,差异均有统计学意义(P<0.05)。结论:妊娠期高血压疾病、羊水过少、妊娠期糖尿病、贫血是胎儿生长受限的高危因素,加强孕期保健及监护,规范治疗产科并发症

  11. Analysis of factors restricting the development of large and medium-sized sports venue in Yunnan Province%制约云南省大中型体育场馆开发因素分析

    Institute of Scientific and Technical Information of China (English)

    史永

    2014-01-01

    In this paper, through the literature material method, investigation method, mathematical statistics, to analyze the factors influencing the development and utilization of large and medium-sized sports venues in Yunnan Province. The property right is not clear through research;economy is relatively backward, lack of inadequate consumption;venue management idea is lag, the overall quality of staff is not high;venue facilities is imperfect, function is relatively simple;the lack of influential brand competition activities and professional teams and other factors fixed, is the main factor that restricts the development of large and medium-sized sports venues in Yunnan province.%本文通过文献资料法、实地考察法、数理统计法、个案分析等研究方法对影响云南省大中型体育场馆开发利用的因素进行综合剖析。通过研究得出产权不清晰;经济较落后,居民消费能力不足;场馆管理者观念滞后,人员整体素质不高;场馆配套设施不完善,功能相对单一;缺乏固定的、有影响力的品牌赛事活动和专业队伍等因素是制约云南省大中型体育场馆开发的主要因素。

  12. Restriction of Helmholtz Model

    Directory of Open Access Journals (Sweden)

    V.M. Polunin

    2014-07-01

    Full Text Available The results of the experimental studies of physical mechanisms of energy dissipation in the oscillating system in which air cavity held by the forces of magnetic levitation is used as the elastic element, and magnetic fluid prepared on the basis of dispersing media with different viscosity level is used as the inertial element are considered in the article. Based on the obtained results the conclusion on the restriction of the applicability of Helmholtz equation, caused by boundary effects is made.

  13. Late gestational nutrient restriction

    DEFF Research Database (Denmark)

    Tygesen, Malin Plumhoff; Nielsen, Mette Olaf; Nørgaard, Peder;

    2008-01-01

    We investigated the effect of 50% nutrient restriction during the last 6 weeks of gestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, ß-hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb birth weight and ewes' lactation performance. Plasma...... changes in feed intake and energy balance. It is concluded that severely reduced nutrient availability in late gestation affects fetal growth in utero and has a prolonged negative effect on lactation performance....

  14. 海洋无脊椎动物细胞培养的制约因素及改进方法%Restrictive Factor and Improved Strategy of Cell Culture from Marine Invertebrates

    Institute of Scientific and Technical Information of China (English)

    张晓燕; 王昌留; 李琳

    2015-01-01

    Attempts to development cell culture from marine invertebrates dated back to 1970s. The cell culture from marine invertebrates lags far behind that from vertebrates,there is no single immortal cell line available from marine invertebrates yet. This review outlines the progress of marine invertebrates’ cell culture,points out restrictive factor,and proposes improved strategy. This article provides the reference on the establishment of im-mortal cell lines from marine invertebrates.%海洋无脊椎动物细胞培养的研究始于20世纪70年代,至今未得到永生化细胞系,远远落后于脊椎动物细胞培养的研究。本文概述了海洋无脊椎动物细胞培养的进展,指出了制约因素,参考脊椎动物的研究成果进而提出了海洋无脊椎动物细胞培养的改进方法,为进一步建立起海洋无脊椎动物的永生化细胞系提供参考。

  15. Methylation and downregulated expression of mac25/insulin-like growth factor binding protein-7 is associated with liver tumorigenesis in SV40T/t antigen transgenic mice, screened by restriction landmark genomic scanning for methylation (RLGS-M).

    Science.gov (United States)

    Komatsu, S; Okazaki, Y; Tateno, M; Kawai, J; Konno, H; Kusakabe, M; Yoshiki, A; Muramatsu, M; Held, W A; Hayashizaki, Y

    2000-01-01

    Restriction landmark genomic scanning for methylation (RLGS-M) was used to detect alterations in DNA methylation associated with murine SV40 T/t antigen-induced hepatocarcinogenesis. An altered locus/spot (S130) was cloned and found to correspond to sequences in the 5' flanking region and 5' portion of the cDNA for the murine mac25/insulin-like growth factor binding protein-7 (Igfbp-7) gene. IGFBPs are believed to be capable of binding insulin, Igf1, and Igf2 and modulating mitogenic effects. Previous studies have shown that Igf2 has an important role in promoting liver tumorigenesis. Quantitative PCR was used to access the methylation status of the NotI site just 5' to the coding region and the expression level of the mac25/igfbp-7 gene. The results indicated that the degree of methylation was inversely related to the expression level and is consistent with a role for DNA methylation in silencing mac25/Igfbp-7 gene expression and function for mac25/Igfbp-7 as a tumor suppressor gene. PMID:10623583

  16. The Examination of China’s New Medical Reform Based on Restrictive Factors in British Medical Reform%基于英国医改制约性因素审视我国新医改

    Institute of Scientific and Technical Information of China (English)

    王演艺

    2014-01-01

    As the first country established universal health insurance in the world, UK has been devoted to construct the fairness and welfare of National Health Service(NHS) with constant development and improvement. It focuses on the reform process of NHS since the beginning of this century and studies the deep factors restricted the reform, compared with the current situation of health care system under China’s new medical reform since 2006, putting forward enlightenment to China’s reform.%作为世界上最早建立全民医疗保障的国家,英国一直致力于其医疗服务系统(NHS)公平性与福利性的构建,不断进行发展与完善。文章重点关注本世纪以来NHS 的改革历程,研究影响其改革成效的深层次制约性因素,同时对照我国2006年启动新医疗改革后国内卫生医疗服务体系的现状,提出其对我国新医改的启示。

  17. 高校网络法制教育效果的制约因素研究%On the Restrictive Factors of Internet Legal Education in Colleges and Universities

    Institute of Scientific and Technical Information of China (English)

    何庆江; 石浩旭

    2015-01-01

    目前很多高校陆续对大学生开展了网络法制教育,但教育效果不佳。制约高校网络法制教育效果的因素主要包括教育者的观念、受教育者的心理、教育的内容与方法、教育环境等。只有针对这些因素提出相应的改进措施,才能提高高校网络法制教育的效果。%Now many colleges and universities have carried out internet legal education for their students in suc-cession, but the effectiveness is poor. There are many factors restricting internet legal education, which mainly in-clude idea of educators, psychology of educatee, content and methods of education, educational environment, etc. In order to improve the effectiveness of internet legal education in colleges and universities, corresponding measures must be put forward.

  18. Discussion on Main Factors Restricting the Sports Scientific Research of College Teachers%浅谈制约高校教师从事体育科研的主要影响因素

    Institute of Scientific and Technical Information of China (English)

    陈秀菊

    2012-01-01

    Taking the physical education department and teachers from 17 universities and 36 vocational colleges in Fujian province as research subject, using the method of literature review, questionnaire, mathematical statis- tics and Pareto analysis, this paper makes analysis on factors restricting the sports scientific research of college students in Fujian province. Based on existing problems, some measurements are put forwarded. The main purpose is to improve the sports scientific research level of college teachers and promote physical education reform.%本研究以福建省17所普通本科院校和36所普通高职院校的体育部门及其教师作为研究对象,运用文献资料法、问卷调查法、数理统计法和帕累托分析法等研究方法,对制约福建省普通高校体育教师从事体育科研的影响因素进行综合研究。针对影响因素提出相应对策,旨在探讨提高福建省高校教师的体育科研水平,推动福建省高校体育教育改革的顺利进行。

  19. License restrictions at Barnwell

    Energy Technology Data Exchange (ETDEWEB)

    Autry, V.R. [S.C. Dept. of Health and Environmental Control, Columbia, SC (United States). Bureau of Radiological Health

    1991-12-31

    The State of South Carolina was delegated the authority by the US Nuclear Regulatory Commission to regulate the receipt, possession, use and disposal of radioactive material as an Agreement State. Since 1970, the state has been the principal regulatory authority for the Barnwell Low-Level Waste Disposal Facility operated by Chem-Nuclear Systems, Inc. The radioactive material license issued authorizing the receipt and disposal of low-level waste contains numerous restrictions to ensure environmental protection and compliance with shallow land disposal performance criteria. Low-level waste has evolved from minimally contaminated items to complex waste streams containing high concentrations of radionuclides and processing chemicals which necessitated these restrictions. Additionally, some waste with their specific radionuclides and concentration levels, many classified as low-level radioactive waste, are not appropriate for shallow land disposal unless additional precautions are taken. This paper will represent a number of these restrictions, the rationale for them, and how they are being dealt with at the Barnwell disposal facility.

  20. 中国职业经理人市场发展的制约因素分析%On the Restricting Factors in the Development of Professional Manager Market in China

    Institute of Scientific and Technical Information of China (English)

    张金艳; 张帆

    2013-01-01

    职业经理人市场是为适应市场经济发展的内在需求而产生的一种新的人力资源配置方式。职业经理人市场的建立和完善涉及到一系列有关因素。相对而言,中国市场经济的建设时期较短,并且具有特殊国情。这决定了不完善的职业经理人价值评价体系、企业主和职业经理人之间的信息不对称、企业主和职业经理人相互信任的缺失、公司治理结构的缺陷和职业经理人市场法律制度的不健全等成为中国职业经理人市场发展的制约因素。%As a new way of human resource allocation, the professional manager market is created to meet the internal demand of the development of market economy. The creation and improvement of professional manager market involves a se-ries of relevant factors. Relatively, China, with special national condition, has established the market economy for a short time period. This determines that the restricting factors for the development of professional manager market in China include the non-perfect value evaluation system for professional managers, asymmetry of information, mutual trust deficiencies between enterprise owners and professional managers, drawback in corporate governance structure and imperfection of relevant legal system and so on.

  1. Problems and Restricting Factor Analysis of Leisure Sports Industry in Shaanxi Province%陕西省休闲体育产业面临的问题及制约因素分析

    Institute of Scientific and Technical Information of China (English)

    姜健

    2012-01-01

    通过对陕西省休闲体育产业面临的问题及制约因素进行深入细致的分析,认为目前面临的主要问题有休闲体育消费市场城乡差别较明显;现有体育场馆设施面向休闲体育市场的开放不够;经营性休闲健身场所与竞赛表演产业发展较成熟,休闲体育培训服务产业较滞后;休闲体育文化产业市场尚待开发。制约陕西省休闲体育产业发展的主要因素包括经济、体制、政策、场地设施、人才等方面。%Through the analysis of problems and factors of Shaanxi leisure sports industry, the paper concludes that the main prob- lem facing leisure sports consumer market gap between urban and rural areas is obvious; Existing sports facilities for leisure sports market opening up enough; Business leisure fitness place and competition demonstration industry development are more mature, leisure sports training service industry is lag; Leisure sports culture industry market is yet to be developed. Restriction of the de- velopment of leisure sports industry of shaanxi province, the main factors including economy, system, policy, the ground equip- ment, personnel, etc.

  2. 限制刑事技术专业实战技能训练开展的因素及对策%The Factors Restricting Combat Skills Training of Criminal Technology Major and the Countermeasures

    Institute of Scientific and Technical Information of China (English)

    张颖

    2014-01-01

    公安院校刑事技术专业的人才培养目标是理论基础扎实、专业知识系统并且实战能力强的应用型复合型刑侦人员,当前刑事犯罪的特点对刑侦人员的实战技能提出了更高的要求。实战技能训练作为培养和提升公安院校刑事技术专业学生实战技能的重要手段和途径,由于受到来自学生、教师以及学校等因素的限制并没有取得理想的教学效果,本文分析了这些因素产生的原因并提出了转变学生观念扭转学习态度,提升教师业务能力和水平,聘请公安机关刑事技术人员为实践教学教官,加强实验室建设,以及建立校外实践训练基地等相应对策。%The training goal of criminal technology major in public security college is to cultivate the practical and versatile talents who have solid theoretical background, professional knowledge system, and outstanding combat ability. However, the characteristics of new crime put forward a higher requirement for the actual combat ability of criminal investigators. As an important way to train and promote the criminal technology majors’ combat ability, the combat skills training fails to receive satisfied teaching effects out of some restrictions from students, teachers and the college. This paper analyses the reasons of these restricted factors and presents the countermeasures accordingly, such as changing the students’ learning idea and attitudes, improving the teachers’ proficiency and teaching level, appointing the criminal technicians in public security organs to be practicing teachers, improving the lab, establishing the practice training base outside school, etc.

  3. Placental Adaptations in Growth Restriction

    Directory of Open Access Journals (Sweden)

    Song Zhang

    2015-01-01

    Full Text Available The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.

  4. 我国公共政策参与中公民层面的制约因素分析%AN ANALYSIS OF FACTORS RESTRICTING CITIZENS FROM PARTICIPATING IN PUBLIC POLICIES

    Institute of Scientific and Technical Information of China (English)

    李占乐

    2011-01-01

    在现代社会,公民积极主动地参与政府的公共政策,除了基于自身利益追求的参与动机外,实现和促进与全体社会成员相联系的公共利益也是一个重要动机。改革开放以后,在公民个体的政策参与逐渐增多的同时,我国以民间组织为主体的各种利益团体参与政府公共政策的活动也逐渐增多。同时在我国公民的公共政策参与过程中存在的问题也十分突出。公共政策参与中公民层面的制约因素主要包括参与意识不强、参与能力不足和参与的组织化程度不高3个方面。%In modern society, citizens actively participate in the government' s public policies. In addition to participation based on the pursuit of self-interests, the achieving and promoting of the public interest involving all members of society can be another important motivation. After the reform and opening up, an increasing number of individual citizens participate in policies and meanwhile more various interest groups in China take part in more policy-related activities with civil organizations as the main body. There exist some prominent problems in the participating process. The factors restricting citizens from participating in public policy include weak sense of participation, lack of capacity for involvement and participation and low degree of organization.

  5. Restrictive Factors and Historical Significance of Rectification Movement in the Later Anti-Japanese War%抗战后期敌后整风的制约因素与历史意义

    Institute of Scientific and Technical Information of China (English)

    向伟

    2015-01-01

    抗战后期,中共在全党开展整风学习运动。处在敌后的各根据地,尽管也都在规定时间内完成整风,但从当时的情况来看,这些根据地的整风受到诸多因素的制约,如党员干部对整风的重要性缺乏认识、敌后环境异常艰苦、党员与干部知识水平较低以及整风脱离实际等。分析敌后整风情况,无论从认识还是实践上,对于如今的党建工作也有一定的启发意义。%In the latter part of the Anti-Japanese War, the Chinese Communists Party carried out the rectification movement. Although the rectification was completed in a short time, from the point of view of the situation at that time, the rectification movement was restricted by many factors , such as the lack of understanding of importance of Party members and cadres ,the difficult environment in the enemy’s rear area, low level of knowledge and rectification from the reality etc. Analysis of rectification situation both from behind enemy lines, understanding and practice, also have certain enlightening significance for today ’s rectification learning.

  6. 制约大学生体育能力发展的因素分析与对策研究%The Factor Analysis and Countermeasure Research of Restricting the University Students Sports Ability

    Institute of Scientific and Technical Information of China (English)

    余丁友

    2011-01-01

    运用问卷和建模等方法,对制约大学生体育能力发展的因素进行了分析讨论。结果表明:在高中阶段,切勿随意调停体育课,学校和家长要积极鼓动他们体育锻炼,努力营造良好的体育氛围;大学阶段,优化教师队伍,大力发展体育社团,加强身体健康的重要性教育;临近毕业阶段,通过各种途径积极提高大学生自我认知能力。同时也提出了针对性的发展对策。%This paper analyzes and disscusses the factors of the restrict on the university sports ability development by the the methods of questionnaire and modeling.The results show that:In the high school stage,PE class can not be stop.Teachers and students parents should actively encouraged student to exercise body and tried to create a fine sports atmosphere.At University phase,optimizing the teachers team,devotes to developing sports organization and strengthen health education of exercising.During the graduation stages,improves the university students' selfcognitive ability by some actively means.Finally,the paper also puts forward corresponding develope countermeasures of how to improve the university students ablity of sports.

  7. 贫困地区民营经济发展的制约因素及对策分析%Restricting Factors for the Growth of Private Economy in Poverty-Stricken Areas and the Strategy

    Institute of Scientific and Technical Information of China (English)

    彭贞贞; 马骥

    2014-01-01

    民营经济发展水平低是贫困地区经济发展不发达的重要原因。制约贫困地区民营经济发展的因素有脱贫致富的思想、人力资源状况、金融生态环境和技术创新水平等。促进贫困地区民营经济发展与脱贫致富必须根据民营经济产业发展需求,大力发展职业教育;优化环境,承接产业转移;创新贫困地区新型城镇化发展机制,推动地区民营经济发展;大力发展交通基础设施,破解民营经济发展瓶颈;创新民营企业管理,做大做强民营经济。%Inadequate development of the private economy is a major reason of economic underdevelopment in poverty-driven areas. Fac-tors restricting the growth of the private economy in these areas include people's lack of eagerness for creating a fortune, human resource shortage, and the poor financial environment and technological innovation ability. To shake off poverty, the areas must develop the private economy by proactively develop vocational education, improve environment for carrying on industry transfer, innovate new-type urbaniza-tion mechanism, enhance the transportation infrastructure construction, and innovate the management of private enterprises.

  8. Factoring

    OpenAIRE

    Lenstra, Arjen K.

    1994-01-01

    Factoring, finding a non-trivial factorization of a composite positive integer, is believed to be a hard problem. How hard we think it is, however, changes almost on a daily basis. Predicting how hard factoring will be in the future, an important issue for cryptographic applications of composite numbers, is therefore a challenging task. The author presents a brief survey of general purpose integer factoring algorithms and their implementations

  9. Very strict selectional restrictions

    CERN Document Server

    Laporte, Eric; Dias, Maria Carmelita P

    2007-01-01

    We discuss the characteristics and behaviour of two parallel classes of verbs in two Romance languages, French and Portuguese. Examples of these verbs are Port. abater [gado] and Fr. abattre [b\\'etail], both meaning "slaughter [cattle]". In both languages, the definition of the class of verbs includes several features: - They have only one essential complement, which is a direct object. - The nominal distribution of the complement is very limited, i.e., few nouns can be selected as head nouns of the complement. However, this selection is not restricted to a single noun, as would be the case for verbal idioms such as Fr. monter la garde "mount guard". - We excluded from the class constructions which are reductions of more complex constructions, e.g. Port. afinar [instrumento] com "tune [instrument] with".

  10. Restricted Factors and Countermeasures for the Development of Chinese Ice Hockey Players%我国冰球运动发展的制约因素及对策

    Institute of Scientific and Technical Information of China (English)

    宁文静; 王淑华

    2013-01-01

    冰球运动是一项冬季体育运动中唯一的球类集体项目,其运动水平可以代表一个国家冬季运动的总体水平。对我国冰球运动现状进行分析,找出目前我国冰球运动存在项目普及萎缩,后备人才短缺;培养体制不完善,场地、器材匮乏;教练员教练水平低,创新意识差;科技投入少,科学化训练水平低等制约因素。提出加大冰球运动后备人才培养力度;制定、完善冰球运动员培养、输送体制;提升冰球运动教练员的整体素质;强化冰球运动科学化训练体系等解决对策,为让冰球运动重新在中国的大地上蓬勃开展起来,打造中国冰球崭新的未来提供参考。%Ice hockey is the only team ball game of winter sports , its sports level can represent the winter sports level of a country .By analyzing the status of Chinese ice hockey , this paper has found out that there are many restricted factors of Chinese ice hockey , such as project popularization declining , shortages of re-served talents;training system is not perfect , lack of venues and equipments;low level of coaches , poor in-novation consciousness;low technology input , low level of scientific training .The paper puts forward that we should strengthen the reserved talents training of ice hockey; outline and perfect the training conveying system of ice hockey players;improve the overall quality of coaches;strengthen scientific training system of ice hockey and other solutions , in order to give a reference for having a great boom in ice hockey in China and creating a new future of Chinese ice hockey .

  11. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...... more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally...

  12. 34周以下早产儿宫外生长发育迟缓发生的影响因素%Risk factors for extrauterine growth restriction in preterm infants with gestational age less than 34 weeks

    Institute of Scientific and Technical Information of China (English)

    曹玮; 张永红; 赵冬莹; 夏红萍; 朱天闻; 谢利娟

    2015-01-01

    ObjectiveTo investigate the correlated factors contributed to extrauterine growth restriction (EUGR) in preterm infants with the gestational age less than 34 weeks.MethodsA total of 694 preterm infants with the gestational ages less than 34 weeks were enrolled. They were classiifed into EUGR and non-EUGR groups by weight on discharge. The perinatal data, growth data, nutritional information and morbidities during hospitalization were compared between the two groups.ResultsEUGR on discharge occurred in 284 (40.9%) out of the 694 infants. The incidence of EUGR in intrauterine growth restriction (IUGR) infants was signiifcantly higher than in non-IUGR infants (P<0.01). The very low birth weight (VLBW) infants had a higher incidence of EUGR than non-VLBW infants (P<0.01). The incidence of EUGR increased with the decreases of gestational age at birth and birth weight (P<0.01). Compared with the non-EUGR group, the fasting time, the duration of parenteral nutrition, the time beginning to feed and the age to achieve full enteral feeds were signiifcantly greater in the EUGR group (P<0.01). The cumulative protein deifcit and cumulative caloric deifcit in the ifrst week of life in the EUGR group were higher than in the non-EUGR group (P<0.05). The incidences of respiratory distress syndrome, apnea, necrotizing enterocolitis and septicemia in the EUGR group were higher than in the non-EUGR group (P<0.05). The logistic regression analysis showed that birth weight, gestational age at birth and IUGR were the independent risk factors for EUGR.ConclusionsThe incidence of EUGR in infants with gestational age less than 34 weeks is high, especially in IUGR or VLBW infants. Early and aggressive nutritional strategy and prevention of apnea and septicemia may facilitate to reduce the occurrence of EUGR.%目的:研究34周以下早产儿宫外生长发育迟缓(EUGR)发生的相关因素。方法选取<34周早产儿694例,根据出院时体重分为EUGR组和非EUGR组,回顾

  13. Geometry of the restricted Boltzmann machine

    OpenAIRE

    Cueto, Maria Angelica; Morton, Jason; Sturmfels, Bernd

    2009-01-01

    The restricted Boltzmann machine is a graphical model for binary random variables. Based on a complete bipartite graph separating hidden and observed variables, it is the binary analog to the factor analysis model. We study this graphical model from the perspectives of algebraic statistics and tropical geometry, starting with the observation that its Zariski closure is a Hadamard power of the first secant variety of the Segre variety of projective lines. We derive a dimension formula for the ...

  14. 制约城市社区老年人参与健身活动的因素研究——基于解释结构模型视角%Research of the Individual Restricting Factors of Elderly Fitness Participation in Urban Community Based on ISM

    Institute of Scientific and Technical Information of China (English)

    任波

    2012-01-01

    This research based on ISM and analyzed the individual restricting factors of elderly fitness participation in urban community.It used the method of matrix to grading the restricting factors.Conclusion shows that the interpretative structural modeling can be classified by three grades.The purpose of this research was to provide strategy analysis and theoretical basis for community managers and elderly fitness activity promoters.%研究制约城市社区老年人健身参与的个人因素,利用ISM模型对各项指标进行分析,运用矩阵的方法对其分级。结果表明,构建的解释结构模型可以分为三级,从而为社区管理者和老年健身活动推广者提供策略分析和理论依据。

  15. 森林资源产权市场制约因素及对策分析——基于供求视角%Analysis on Forest Resource Property Market's Restriction Factors and Countermeasures: From the Perspective of Supply and Demand

    Institute of Scientific and Technical Information of China (English)

    乔永平; 聂影

    2012-01-01

    目前森林资源产权市场仍处于起步阶段,存在着众多制约市场供求双方的因素.制约需求的因素包括森林资源产权制度不完善、森林资源风险防范机制不健全、林业融资难、林业比较利益低;制约供给的因素包括政策法规不完善、信息不完备、交易成本高、非农就业机会少、社会保障制度不健全等;通过市场中介间接影响供求的因素包括市场中介组织缺乏等.本研究给出了强化森林资源产权市场机制的对策建议.%Current forest resource property market is still at the initial stage and there are many restricting factors that affect both the supply and the demand. The factors restricting the demand are forest resource property systems being imperfect, forest resource risk prevention mechanism being incomplete, forestry financing being difficult, forestry comparative rate of profit being low and so on; the factors restricting the supply include concerning law and policies being imperfect, information being incomplete, trading cost being high, non-agricultural job chance being low, social security system being imperfect and so on; to make it worse, imperfect intermediary organization turns out to be one of the restricting factors affect both the supply and the demand. This research offers some countermeasure suggestions of strengthening forest resource property market mechanism.

  16. Nutrient restrictive factors, nutrient absorption and accumulation of red kidney bean%红芸豆养分限制因子及养分吸收、积累和分配特征研究

    Institute of Scientific and Technical Information of China (English)

    韩彦龙; 晋凡生; 郑普山; 李晓平; 李洁; 李海金

    2016-01-01

    AbstractWith important economical and nutritional values, kidney bean (Phaseolus vuglaris) is one of the main grain crops in China. Recently, the planting area of red kidney bean has been gradually increasing in Shanxi Province, China. However, the nutrient absorption characteristics and limiting factors of kidney bean was still not very clear. Nitrogen (N), phosphorus (P) and potassium (K) are essential nutrients for plant growth, and knowledge on periodic uptake, accumulation and allocation of N, P and K in different organs of kidney bean is important to implement nutrient management practices to ensure its’ sustainable production. There were several studies on effect of the fertilization and nitrogen application on yield of kidney bean. However, few studies have investigated the nutrient accumulation and distribution characteristics of kidney bean. In this study, field experiment was conducted with different nutrient application (N absence, P absence, K absence, NPK application and no fertilizer) using the red kidney bean variety ‘British Red’ as the materials in 2014. The nutrient restrictive factors, dry matter accumulation and nutrient uptake and accumulation of red kidney bean were investigated. The samples of NPK application treatment at different growth stages were collected for determining dry matter and nutrient contents in different organs, to illustrate the law of nutrient absorption. This is beneficial to provide theoretical basis for rational fertilization and high yield cultivation of red kidney bean. The results showed that NPK application treatment significantly increased yield of red kidney bean compared to absence of N, P, or K and no fertilizer treatments. Compared to NPK application treatment, yields of N-, P- or K-absence decreased by 14.2%, 8.0% and 11.3%, respectively, which indicated that the order of nutrient restrictive factors of red kidney bean yield was N > K > P. The dry matter accumulation rate of red kidney bean increased

  17. Epigenetic regulation of caloric restriction in aging

    Directory of Open Access Journals (Sweden)

    Daniel Michael

    2011-08-01

    Full Text Available Abstract The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modification, are believed to dynamically influence chromatin structure, resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging and potential extension of a healthy lifespan in humans. Enhanced understanding of the important role of epigenetics in the control of the aging process through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases.

  18. Repletion of TNFα or leptin in calorically restricted mice suppresses post-restriction hyperphagia

    Science.gov (United States)

    Hambly, Catherine; Duncan, Jacqueline S.; Archer, Zoë A.; Moar, Kim M.; Mercer, Julian G.; Speakman, John R.

    2012-01-01

    SUMMARY The causes of post-restriction hyperphagia (PRH) represent a target for drug-based therapies to prevent obesity. However, the factors causing PRH are poorly understood. We show that, in mice, the extent of PRH was independent of the time under restriction, but depended on its severity, suggesting that PRH was driven by signals from altered body composition. Signals related to fat mass were important drivers. Circulating levels of leptin and TNFα were significantly depleted following caloric restriction (CR). We experimentally repleted their levels to match those of controls, and found that in both treatment groups the level of PRH was significantly blunted. These data establish a role for TNFα and leptin in the non-pathological regulation of energy homeostasis. Signals from adipose tissue, including but not limited to leptin and TNFα, regulate PRH and might be targets for therapies that support people engaged in CR to reduce obesity. PMID:21954068

  19. How harmful are adaptation restrictions

    OpenAIRE

    Bruin, de, B.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  20. Remarks on restricted Nevanlinna transforms

    CERN Document Server

    Jankowski, Lech

    2010-01-01

    The Nevanlinna transform K(z), of a measure and a real constant, plays an important role in the complex analysis and more recently in the free probability theory (boolean convolution). It is shown that its restriction k(it) (the restricted Nevanlinna transform) to the imaginary axis can be expressed as the Laplace transform of the Fourier transform (characteristic function) of the corresponding measure. Finally, a relation between the Voiculescu and the boolean convolution is indicated.

  1. Alteration of placental haemostatic mechanisms in idiopathic intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Jaime Eduardo Bernal Villegas

    2012-08-01

    Full Text Available Intrauterine growth restriction is a complication of pregnancy with a high probability of perinatal morbidity and mortality. It appears tobe caused by abnormal development of placental vasculature. Haemostatic processes are important for the development of the placenta,and an imbalance between procoagulant and anticoagulant factors has been associated with risk of intrauterine growth restriction.Objective. To evaluate coagulation abnormalities in placenta of pregnancies complicated with idiopathic intrauterine growth restriction.Materials and methods. Five placentas from pregnancies with idiopathic intrauterine growth restriction were compared to 19 controls.We performed gross and histological examination of the placenta. Analysis was made of both mRNA expression by real-time PCRand protein by ELISA of tissue factor and thrombomodulin in placental tissue. Results. Results based on histological evaluation wereconsistent with an increased prothrombotic state in placentas from pregnancies with idiopathic intrauterine growth restriction, andthrombosis of chorionic vessels was the most important finding. The study showed an increased expression of tissue factor protein(p=0.0411 and an increase in the ratio of tissue factor/thrombomodulin mRNA (p=0.0411 and protein (p=0.0215 in placentas frompregnancies with idiopathic intrauterine growth restriction. There were no statistically significant differences neither between cases andcontrols in the mRNA levels of tissue factor or thrombomodulin nor at the protein level of thrombomodulin. Conclusion. Evidence ofalteration of local haemostatic mechanisms at the level of the placenta, including abnormal expression of tissue factor and tissue factor/thrombomodulin ratio, in pregnancies that occur with idiopathic intrauterine growth restriction is presented.

  2. Neutron inelastic scattering from {sup 4}He in restricted geometries

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, M.R. [Keele Univ. (United Kingdom). Dept. of Physics; Sokol, P.E. [Dept. of Physics, Pennsylvania State Univ., University Park, PA (United States); Azuah, R.T. [Keele Univ. (United Kingdom). Dept. of Physics]|[Rutherford Appleton Lab., Chilton, Didcot (United Kingdom); Stirling, W.G. [Keele Univ. (United Kingdom). Dept. of Physics; Adams, M.A. [Rutherford Appleton Lab., Chilton, Didcot (United Kingdom)

    1995-08-01

    When liquid {sup 4}He is condensed in porous aerogel glass (typical pore size {approx}5000 A), many of the superfluid properties are significantly altered. Measurements have been made of the dynamic structure factor S(Q,{omega}) of liquid {sup 4}He in restricted geometries. The collective phonon-roton excitations are shown to have an intrinsic broadening associated with the restricted geometry. The temperature dependence of the excitation spectrum is discussed. (orig.).

  3. Photoperiod interacts with food restriction on performance in the Barnes maze in female California mice

    OpenAIRE

    Steinman, Michael Q.; Crean, Katie K.; Trainor, Brian C.

    2010-01-01

    Food restriction has been reported to have positive effects on cognition. This study examines how another environmental factor, daylength, can alter the impact of food restriction on the brain and behavior. Female California mice (Peromyscus californicus), housed on either long days (16L:8D) or short days (8L:16D) were restricted to 80% of their normal baseline food intake or provided food ad libitum. Testing in a Barnes maze revealed that the effects of food restriction depend on photoperiod...

  4. Genetics Home Reference: familial restrictive cardiomyopathy

    Science.gov (United States)

    ... Home Health Conditions familial restrictive cardiomyopathy familial restrictive cardiomyopathy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Familial restrictive cardiomyopathy is a genetic form of heart disease. For ...

  5. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Siddharth Gautam; S Mitra; R Mukhopadhyay

    2008-10-01

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time scales involved in the motion and the geometry of motion can be studied using QENS. Molecular dynamics (MD) simulation not only provides insight into the details of the different types of motion possible but also does not suffer limitations of the experimental set-up. Here we report the effect of confinement on molecular dynamics in various restricted geometries as studied by QENS and MD simulations: An example where the QENS technique provided direct evidence of phase transition associated with change in the dynamical behaviour of the molecules is also discussed.

  6. Telomere Restriction Fragment (TRF) Analysis

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al., 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al., 1990; Ouellette et al., 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  7. CDRL - company dose restriction level

    International Nuclear Information System (INIS)

    For a number of year's close constraints and controls have been used as effective measures in aiding restricting exposure to ionising radiation. Predecessor companies to British Energy Generation (BEG) originally established the Company Dose Restriction Level (CDRL) as a consequence of the revision of risk estimates, then with the revised Ionising Radiations Regulations 1999 (IRR99) the CDRL for BEG was also revised. The background, influences and consequences of CDRL appliance in a commercial organisation in calendar year 2000/1 are presented below. (author)

  8. HFB in a restricted space

    International Nuclear Information System (INIS)

    A restricted Hartree-Fock-Bogoliubov method is developed with a restriction on the angular momenta of the Cooper pairs that conform the vacuum (SD or SDG). The method is applied to 176Yb. The quadrupole moment in the SD subspace is found to be 80% for neutrons and 91% for protons of its value in the full space. The inclusion of the G part of the Cooper pairs improves that agreement. The descriptions in terms of boson condensate and coherent states are discussed. (author)

  9. APOBEC3G-induced hypermutation of human immunodeficiency virus type-1 is typically a discrete "all or nothing" phenomenon

    DEFF Research Database (Denmark)

    Armitage, Andrew E; Deforche, Koen; Chang, Chih-Hao;

    2012-01-01

    -lethal frequencies that could increase viral diversification. We show in vitro that limiting-levels of hA3G-activity (i.e. when only a single hA3G-unit is likely to act on HIV) produce hypermutation frequencies similar to those in patients and demonstrate in silico that potentially non-lethal G-to-A mutation rates......" phenomenon. Thus, therapeutic measures that inhibit the interaction between Vif and hA3G will likely not increase virus diversification but expand the fraction of hypermutated proviruses within the infected host....

  10. Space-restricted attribute grammars

    DEFF Research Database (Denmark)

    Schmidt, Erik Meineche

    1980-01-01

    Restricting the size of attribute values, relative to the length of the string under consideration, leads to a model of attribute grammars in which grammars with both inherited and synthesized attributes can be significantly more economical than grammars with synthesized attributes only....

  11. Restricted Morgan’s problem

    Institute of Scientific and Technical Information of China (English)

    陈树中; 曹立

    1996-01-01

    A new list of regular feedback invariant integers called right independent orders is introduced.That the restricted Morgan’s problem is equivalent to a kind of nonlinear algebraic equations is proved and the condition that the nonlinear algebraic equations degenerate into linear algebraic equations is given.

  12. Restrictive dermopathy and fetal behaviour

    NARCIS (Netherlands)

    Mulder, EJH; Beemer, FA; Stoutenbeek, P

    2001-01-01

    We report three siblings from consecutive pregnancies affected with restrictive dermopathy (RD). During the second pregnancy, fetal behavioural development and growth were studied extensively using ultrasound at 1-4 week intervals. Dramatic and sudden changes occurred in fetal body movements and gro

  13. Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Wood Richard J

    2006-05-01

    Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

  14. 甘肃省少数民族地区包容性增长制约因素分析——基于“十二五”的历史方位%Analysis about restrictive Factors in Minority Area of GanSu's Inclusive Growth --Based on the Historical Position of the Period from the Year 2011 to 2015

    Institute of Scientific and Technical Information of China (English)

    张克政

    2012-01-01

    包容性增长是“十二五”时期甘肃省少数民族地区发展面临的重大课题。经济基础薄弱、发展任务繁重、自然条件恶劣、地理区住劣势明显、基础设施落后、社会事业发展滞后、人才资源匮乏、制度不完善、社会不公是制约“十二五”时期少数民族地区包容性增长的主要因素。深入分析少数民族地区包容性增长的制约因素,是推动少数民族地区包容性增长的前提。%Inclusive growth is a great subject to minority area of GanSu in the period of the year 2011 to 2015. The unsubstantial economic foundation, heavy development task, bad natural conditions, evident geographical location disadvantages, behindhand infrastructure, hysteretic development of social undertakings, deficient resources of human talents, ineompletcd system and social injustice are major restrictive factors which will restrict minority area of Gansu's inclusive growth in the period from the year 2011 to 2015. In-depth analysis of the restrictive factors about minority area of GanSu's inclusive growth is the precondition of pushing forward minority area of GanSu's inclusive growth.

  15. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than...

  16. 制约少数民族生态移民可持续发展的因素探究%Probing into the Factors Restricting the Sustainable Development of the Minority Ecological Migration

    Institute of Scientific and Technical Information of China (English)

    金莲; 王永平; 周丕东; 黄海燕

    2012-01-01

    To realize the sustainable development of the minority ecological migration, we must consider four constraints that are social factors, economical factors, ecological factors and own factors. Social factors involve the constraints of government, community, enterprise and NGO. Economic factors mainly include three aspects that are economic development foundation, the development level of the industry and the urbanization level. Ecological factors are considered from the angle of natural conditions, such as land and water. Economic conditions, cultural quality, ideology and family structure of eco-migrants themselves also affect the sustainable development of the minority ecological migration.%实现可持续发展受到社会、经济、生态及移民自身方面因素的制约,其中社会因素,涉及政府、社区、企业及民间组织四个方面;经济因素主要包括经济发展基础、产业发展水平和城镇化水平三个方面;生态因素主要是从自然条件(如土地、水等资源)的角度去考虑其制约因素;移民自身的经济条件、文化素质、思想观念和家庭结构也是影响少数民族生态移民可持续发展的因素.

  17. Requirements for nucleocapsid-mediated regulation of reverse transcription during the late steps of HIV-1 assembly.

    Science.gov (United States)

    Racine, Pierre-Jean; Chamontin, Célia; de Rocquigny, Hugues; Bernacchi, Serena; Paillart, Jean-Christophe; Mougel, Marylène

    2016-01-01

    HIV-1 is a retrovirus replicating within cells by reverse transcribing its genomic RNA (gRNA) into DNA. Within cells, virus assembly requires the structural Gag proteins with few accessory proteins, notably the viral infectivity factor (Vif) and two copies of gRNA as well as cellular factors to converge to the plasma membrane. In this process, the nucleocapsid (NC) domain of Gag binds to the packaging signal of gRNA which consists of a series of stem-loops (SL1-SL3) ensuring gRNA selection and packaging into virions. Interestingly, mutating NC activates a late-occurring reverse transcription (RT) step in producer cells, leading to the release of DNA-containing HIV-1 particles. In order to decipher the molecular mechanism regulating this late RT, we explored the role of several key partners of NC, such as Vif, gRNA and the cellular cytidine deaminase APOBEC3G that restricts HIV-1 infection by targeting the RT. By studying combinations of deletions of these putative players, we revealed that NC, SL1-SL3 and in lesser extent Vif, but not APOBEC3G, interplay regulates the late RT. PMID:27273064

  18. Study on the Restricting Factors and Countermeasures in Resource - based Industries Green Development of Poyang Lake Ecological Economic Zone%鄱阳湖生态经济区资源型产业绿色发展制约因素及对策研究

    Institute of Scientific and Technical Information of China (English)

    李胜连

    2014-01-01

    鄱阳湖生态经济区作为国家的战略发展区域,应该具有超前思维,大力发展绿色产业,而资源型产业容易造成外部不经济,因此更需要健康、绿色发展。本文利用 AHP 方法对环鄱区资源型产业绿色发展的制约因素进行分层排序,得到如下结论:技术因素和生态因素是主要制约因素;制约因素排名前5位的分别是:空气质量、政府及社会第三方的技术监督、水资源质量、外部不经济补救成本、绿色检测技术的推广与应用。%As a strategic development areas of the country ,Poyang Lake Ecological Economic Zone should have advanced thinking ,to vigorously develop the green industry .But the resources industry is easy to cause the external diseconomy , therefore it need more healthy and green development .In this paper ,by using the AHP method ,hierarchical ranking con-straints of Poyang Lake Ecological Economic Zone is conducted and conclusion is as follows :technical factors and ecological factors are the main restricting factors and the top five restricting factors should be air quality ,the technological supervision of the third party government and society ,the quality of water resources ,external non economic recovery cost ,promotion and application of green detection technology .

  19. Management of fetal growth restriction

    OpenAIRE

    Alberry, M; Soothill, P

    2007-01-01

    Fetal growth restriction (FGR) is challenging because of the difficulties in reaching a definitive diagnosis of the cause and planning management. FGR is associated not only with a marked increased risk in perinatal mortality and morbidity but also with long‐term outcome risks. Combinations of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables allow a comprehensive fetal evaluation of FGR. However, no evidence supports that the u...

  20. 制约我国地方性国有资产证券化的因素与对策研究%The Research on the Restrict Factors to Local State- owned Assets Securitization and Countermeasure

    Institute of Scientific and Technical Information of China (English)

    李国义; 杨果

    2012-01-01

    Securitization is the local state - owned assets important means for increment. But some factors exist in the local state - owned asset securitization process, including the subjective and objective factors, the subjective factors are enor of understanding in state - owned asset function, efficiency of public ownership theory. In order to promote the local state- owned asset securitizafion, it is necessary to undertake an analysis to these elements, put forward according to these factors the countermeasures to solve the problems, to further promote the local state - owned assets securitization. We can take the induction, inference analysis method to study. Securitization of state - owned assets, should from the dynamic asset expanded to static asset, from artificial assets expanded to natural assets.%证券化是地方性国有资产保值增值的重要手段。但是在地方性国有资产证券化过程中存在一些制约因素,包括主观因素和客观因素,其中主观因素主要是在国有资产功能、公有制效率等理论方面存在认识偏差。为了顺利推进地方性国有资产证券化工作,有必要对这些因素进行分析,针对这些因素提出解决问题的对策,进一步推进地方性国有资产证券化。可以采取归纳、推理分析方法进行研究。可证券化的国有资产范围,应该从动态资产扩大到静态资产,从人工资产扩大到自然资产。

  1. "Green consumption" restricting factors: Analysis based on five dimensional framework%"绿色消费"的制约因素研究:基于五维框架的分析

    Institute of Scientific and Technical Information of China (English)

    付兆锋

    2015-01-01

    绿色消费是我国生态文明建设的基本要求.如何推进绿色消费是现实中极为关注而理论上亟待解决的难题.本文从市场需求、消费意识、消费价格、企业生产、消费环境五个维度构建绿色消费的影响因素体系,采用DEMATEL方法研究绿色消费的制约因素.有鉴于此,政府应着力于制定绿色消费政策拉动市场需求,改善绿色消费环境.%The green consumption is the basic requirement of ecological civilization construction in our country. How to promote green consumption is a difficult problem to be solved. In this paper, from the market demand, consumer consciousness, consumer prices five dimensions, enterprise production, consumption environment, build system of the influence factors of green consumption, using DEMATEL method to study the factors of the green consumption. For this reason, the government should focus on green consumption policy driven by market demand, improve the environment of green consumption.

  2. Electromagnetic Fields Restrictions and Approximation

    CERN Document Server

    Katsenelenbaum, Boris Z

    2003-01-01

    The fields scattered by metallic bodies or radiated by some types of antennas are created by the surfaces currents and therefore they are subject to some restrictions. The book is the first one where the properties of these fields are investigated in details. The properties have the important significance for the antenna synthesis, body shape reconstruction and other diffraction problems. The material of the book lies in the meetingpoint of the antenna theory, highfrequency electrodynamics and inverse scattering problems. The author is an internationally renowned investigator in the field of e

  3. Restrictions on trade in distribution services

    OpenAIRE

    Kaleeswaran Kalirajan

    2001-01-01

    Identifies and quantifies restrictions affecting domestic and international trade in distribution services - mainly wholesaling and retailing - in 38 economies, including Australia. The paper also explores the price and cost implications of restrictions in food distribution services.

  4. Bronchial Responsiveness in Patients with Restrictive Spirometry

    OpenAIRE

    Keddissi, Jean I.; Elya, Marwan K.; Farooq, Saif U.; Youness, Houssein A.; Kellie R. Jones; Ahmed Awab; Kinasewitz, Gary T.

    2013-01-01

    Background. Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. Methods. Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defi...

  5. 42 CFR 73.13 - Restricted experiments.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Restricted experiments. 73.13 Section 73.13 Public... SELECT AGENTS AND TOXINS § 73.13 Restricted experiments. (a) An individual or entity may not conduct a restricted experiment with a HHS select agent or toxin unless approved by and conducted in accordance...

  6. Restrictive Cardiomyopathy: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Bilal Bin Abdullah*, Mehboob.M.Kalburgi, Sahana Shetty and Satyasrinivas

    2011-04-01

    Full Text Available We report a 28 years old male presenting with heart failure. A thorough clinical evaluation directed us towards restrictive heart disease. Doppler echocardiographic study was used as a main modality of diagnosis and cardiac catheterization confirmed the diagnosis of idiopathic restrictive cardiomyopathy. We express the contribution of clinical findings and appropriate diagnostic measures in approaching a case of Restrictive cardiomyopathy (RCM.

  7. 50 CFR 648.204 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession restrictions. 648.204 Section... Atlantic Herring Fishery § 648.204 Possession restrictions. (a) A vessel must be issued a valid limited... with no possession restriction from any of the herring management areas defined in §...

  8. Profiling of micrometer-sized laser beams in restricted volumes

    DEFF Research Database (Denmark)

    Miroshnychenko, Yevhen; Nielsen, Otto; Thorsen, Aske;

    2012-01-01

    micrometers across the measuring volume. We characterize the performance of the method and experimentally demonstrate profiling of micrometer-sized laser beams. We discuss the limiting factors and routes toward a further increase of the resolution and beam profiling in even more restricted volumes. Finally......, as an application example, we present profiling of laser beams inside a micro ion trap with integrated optical fibers.......We present a method for determining the three-dimensional intensity distribution of directed laser radiation with micrometer resolution in restricted volumes. Our method is based on the incoupling and guiding properties of optical fibers, with the current version requiring only a few hundred...

  9. 试析贫困大学生就业难的深层社会因素%A Deep Social Factor Analysis on the Restriction of Poor College Students Employment Difficulty

    Institute of Scientific and Technical Information of China (English)

    彭仲生; 罗筑华

    2012-01-01

    当前大学生就业难已经成了大学生、学生家长、高等学校及社会共同的感受和普遍关注的问题,而作为大学生中的弱势群体——贫困大学生的就业则更是得到了有关各方的高度重视.为进一步探明当前贫困大学生就业难的潜因,为今后解决贫困大学生就业问题打好前期基础,文章对贫困大学生就业困难的深层社会因素进行了初步分析,并提出了一些可操作性的对策和措施.%Employment difficulty of college students has become consensus and concern of college students, parents, colleges and society in recent years, and for poor college students, the vulnerable group of the university, their employment problem has attracted more intensive attention from the society. In order to explore the potent factors of employment difficulty of poor college students and to make a good preparation for the solution to this problem, this article attempts to make an analysis of the reasons and countermeasure of poor college students' employment difficulty from the perspective of society.

  10. 低出生体重早产儿宫外发育迟缓的相关因素分析%Related factors of extrauterine growth restriction in low birth weight preterm children

    Institute of Scientific and Technical Information of China (English)

    廖文君

    2014-01-01

    目的:探讨胎龄≤32周低出生体重早产儿宫外发育迟缓(EUGR)发生率及其相关影响因素。方法纳入126例胎龄≤32周低出生体重早产儿,记录胎龄(超声或出生时成熟度分析数据)、出生时体重、身长、头围、性别、是否低于胎龄儿、是否存在呼吸窘迫综合征、最大生理性体重减少率、恢复出生体重的天数、起始肠内喂养时间、完全肠内喂养时间(每天奶量>100 ml/kg·d),37~42周时测定早产儿体重、身长、头围,以体重、身长和头围计,分析EUGR发生率、其危险因素以及适于胎龄儿(AGA)和低于胎龄儿(SGA) EUGR发生率。结果 EUGR组胎龄、出生体重、出生身长、出生头围均低于非EUGR组(均P100 ml/kg·d) were recorded. During 37~42 weeks, weight, length, head circumference, body weight, length and head circumference of premature children were measured. Incidence of EUGR and risk factors, and incidences of EUGR in appropriate for gestational age children (AGA) and small for gestational age children (SGA) were analyzed. Results The gestational age, birth weight, birth length, and head circumference at birth of EUGR group were lower than those of the non-EUGR group (all P<0.01), while the rate of weight loss (%), time to regain birth weight, time for starting enteral feeding and giving full enteral feeding were greater than those of non-EUGR group (all P<0.01). The proportion of SGA was significantly greater than that of non-EUGR group (all P<0.05). Based on weight, length, head circumference, incidences of EUGR in all newborns were 47.6%, 39.7%and 4.8%. Toatally, extrauterine growth retardation rate of SGA was significantly higher than that of AGA (all P<0.01).Gestational age, birth weight, recovery time, and time for full enteral feeding were closely related with EUGR. Conclusion Gestation-al age, intrauterine growth retardation, poor nutritional intake and RDS are still the risk factors of EUGR in premature

  11. On Restricting Factors and Countermeasures of the Development of Carrageenan%我国卡拉胶生产发展制约因素及其对策的探讨

    Institute of Scientific and Technical Information of China (English)

    郭善慧; 关键

    2014-01-01

    卡拉胶用作天然食品添加剂已有多年的历史,它是一种无毒而又不能被人体消化的植物纤维,用途十分广泛。国外的卡拉胶商业性生产是从20世纪20年代开始的。我国则从1985年开始生产商业用卡拉胶,其中80%用于食品或与食品有关的工业。随着食品、医疗等行业发展,国内外市场对卡拉胶需求不断扩大,但卡拉胶行业在蓬勃发展的同时遇到瓶颈。本文主要通过对卡拉胶生产发展制约因素的研究,以探讨破解瓶颈的方法和策略。%Carrageenan is used as a natural food additive has a long history, it is the plant fiber which is a non-toxic and can not be digested by, use isvery extensive. Carrageenan demand has continued to expand, but in recent years the development of carrageenan bottleneck of highlights. In this paper , through the research on the development of carrageenan production factors, to explore the methods and strategies of breaking the bottleneck.

  12. Observability in electric power networks: a method of ways of factorization in state estimation with equality restrictions; Observabilidade em redes de energia: um metodo de caminhos de fatoracao em estimacao de estado com restricoes de igualdade

    Energy Technology Data Exchange (ETDEWEB)

    Vicentino, Flavio Antonio

    1997-07-01

    A theory of network observability that mixes graph concepts and factorization of the gain matrix G has been recently developed. It uses data already available in Power System Operating Centers. That theory is easy to understand and implement and does not require subroutines other than the ones used in static state estimation. However, this new theory has been implemented only for the case of state estimation in Normal Equation Formulation (N E). However, the N E Method presents some inherent numerical difficulties. Such numerical difficulties are usually related to the disparity in the measurements weights (high values for zero-injections measurements and low values for pseudo-measurements) and the presence of short lines in the network, as well. In order to solve such numerical difficulties, new methods have come up, such as: Normal Equation Method with Equality Constraints (N E/C), where Lagrange's Multiplier Method can be applied to minimize a function while satisfying a set of constraints; Hachtel's Method, which is formulated the same way as N E/C Method, although an equation of residual vector is introduced in solution process; Hybrid Method, which is a general formulation behaving as the N E/C Method at one extreme, and as Hachtel's Method at the other. Thus, the aim of this work is to treat the adaptation of the network observability Method by using path graphs, with the state estimation in the form of a minimization problem with equality constraints. As the Hybrid Method is a generalization form of the state estimator with constraints, this formulation is used to develop the proposed theory. Extreme case (as the pure Hachtel's Method) are also considered. (author)

  13. Factors Restricting the Healthy Development of Non-governmental Institutions of Higher Learning from the Perspective of Public Spirit%从公共精神看民办高校健康发展的制约因素

    Institute of Scientific and Technical Information of China (English)

    薛金玲; 宋秋蓉

    2012-01-01

      公共精神是西方现代公民文化的核心观念,指在承认个人独立自主性的前提下,公民所拥有的着眼于社会整体的公共精神。目前我国部分民办高校办学者缺乏诚信自律意识、法制规则意识、公共责任意识等公共精神,并在一定程度上存在着背离公共精神的家族化意识。办学者缺乏相关的公共精神,是制约民办高校健康发展的重要因素。我国君主专制制度和儒家文化的负面效应是办学者缺乏公共精神的主要原因。昔日私立南开大学校长张伯苓所拥有的公共精神,值得当今民办高校的办学者学习。%  Public spirit, as the core concept of modern citizen culture in western world , refers to the consciousness of society as a whole held by citizens with the acknowledgement of full personal independence and autonomy .Some of the current administrators in non-governmental institutions of higher learning in China lack the public spirit of the awareness of integrity and self -discipline, regulation and legislation, as well as the sense of public responsibility .To some extends, they depart from public spirit and be-lieve in family consciousness.This is one of the main factors that prevent non-governmental institutions of higher learning from their healthy developments .The negative effect from China's autocratic monarchy and Confucian culture is one of the main reasons for administrators'lack of public spirit.The lifelong affection of public spirit of Zhang Boling , a former president of Nankai Uni-versity, is well worth learning by his peers today .

  14. 21世纪初波兰的东方政策及其制约因素%Poland’s Eastern Policy and Its Restricting Factors in the Early 21st Century

    Institute of Scientific and Technical Information of China (English)

    赵艳霞; 唐更田

    2013-01-01

      21世纪初,随着波兰“入约加盟”,东方问题开始凸显,积极活跃的东方政策遂成为波兰的优先外交政策。地缘政治与现实利益、历史积淀与文化传统以及精英集团的政策理念与公众情绪等各种复杂的国内外因素,决定21世纪波兰的东方政策仍以对俄政策为核心,防范俄罗斯对波兰的威胁是其主要战略意图,并以此为基础在一定程度上决定着波兰对乌克兰、白俄罗斯和南高加索等东欧中亚国家的政策。而欧盟、美国则成为波兰推行东方政策的主要借助力量,实现欧盟东方政策的“波兰化”是波兰实现东方政策的最理想方式。%In the early 21st century, with Poland’s accession to NATO, Eastern problem became prominent. An active eastern policy became a prior foreign policy. In the 21st century, Poland’s eastern policy still kept Russia as the center, which was decided by complex factors at home and abroad like geopolitics, practical interests, historical accumulation, cultural tradition, elite crew’s policy principle and public mood. Preventing Russian threaten was the main strategic idea, which also decided Poland’s policies toward Ukraine, Belarus and the Southern Caucasus, and other Central Asian Eastern Europe countries. EU and U.S.A. became Poland’s main relay powers to push“eastern policy”. Therefore, the“Polonization”of EU’s“eastern policy”was the best way to realize its own“eastern policy”.

  15. Paternally Inherited IGF2 Mutation and Growth Restriction.

    Science.gov (United States)

    Begemann, Matthias; Zirn, Birgit; Santen, Gijs; Wirthgen, Elisa; Soellner, Lukas; Büttel, Hans-Martin; Schweizer, Roland; van Workum, Wilbert; Binder, Gerhard; Eggermann, Thomas

    2015-07-23

    In humans, mutations in IGF1 or IGF1R cause intrauterine and postnatal growth restriction; however, data on mutations in IGF2, encoding insulin-like growth factor (IGF) II, are lacking. We report an IGF2 variant (c.191C→A, p.Ser64Ter) with evidence of pathogenicity in a multigenerational family with four members who have growth restriction. The phenotype affects only family members who have inherited the variant through paternal transmission, a finding that is consistent with the maternal imprinting status of IGF2. The severe growth restriction in affected family members suggests that IGF-II affects postnatal growth in addition to prenatal growth. Furthermore, the dysmorphic features of affected family members are consistent with a role of deficient IGF-II levels in the cause of the Silver-Russell syndrome. (Funded by Bundesministerium für Bildung und Forschung and the European Union.).

  16. Restriction of Retroviral Replication by Tetherin/BST-2

    Directory of Open Access Journals (Sweden)

    Jason Hammonds

    2012-01-01

    Full Text Available Tetherin/BST-2 is an important host restriction factor that limits the replication of HIV and other enveloped viruses. Tetherin is a type II membrane glycoprotein with a very unusual domain structure that allows it to engage budding virions and retain them on the plasma membrane of infected cells. Following the initial report identifying tetherin as the host cell factor targeted by the HIV-1 Vpu gene, knowledge of the molecular, structural, and cellular biology of tetherin has rapidly advanced. This paper summarizes the discovery and impact of tetherin biology on the HIV field, with a focus on recent advances in understanding its structure and function. The relevance of tetherin to replication and spread of other retroviruses is also reviewed. Tetherin is a unique host restriction factor that is likely to continue to provide new insights into host-virus interactions and illustrates well the varied ways by which host organisms defend against viral pathogens.

  17. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

    C S Srivatsan; M V N Murthy; R K Bhaduri

    2006-03-01

    In a recent paper (Tran et al, Ann. Phys. 311, 204 (2004)), some asymptotic number theoretical results on the partitioning of an integer were derived exploiting its connection to the quantum density of states of a many-particle system. We generalise these results to obtain an asymptotic formula for the restricted or coloured partitions $p_{k}^{s} (n)$, which is the number of partitions of an integer into the summand of th powers of integers such that each power of a given integer may occur utmost times. While the method is not rigorous, it reproduces the well-known asymptotic results for = 1 apart from yielding more general results for arbitrary values of .

  18. Stillbirth and fetal growth restriction.

    Science.gov (United States)

    Bukowski, Radek

    2010-09-01

    The association between stillbirth and fetal growth restriction is strong and supported by a large body of evidence and clinically employed for the stillbirth prediction. However, although assessment of fetal growth is a basis of clinical practice, it is not trivial. Essentially, fetal growth is a result of the genetic growth potential of the fetus and placental function. The growth potential is the driving force of fetal growth, whereas the placenta as the sole source of nutrients and oxygen might become the rate limiting element of fetal growth if its function is impaired. Thus, placental dysfunction may prevent the fetus from reaching its full genetically determined growth potential. In this sense fetal growth and its aberration provides an insight into placental function. Fetal growth is a proxy for the test of the effectiveness of placenta, whose function is otherwise obscured during pregnancy.

  19. Asymptotics for restricted integer compositions

    CERN Document Server

    Malandro, Martin E

    2011-01-01

    We study the compositions of an integer n where the part sizes of the compositions are restricted to lie in a finite set. We obtain asymptotic formulas for the number of such compositions, the total and average number of parts among all such compositions, and the total and average number of times a particular part size appears among all such compositions. Several of our asymptotics have the additional property that their absolute errors---not just their percentage errors---go to 0 as n goes to infinity. Along the way we also obtain recurrences and generating functions for calculating several of these quantities. Our asymptotic formulas come from the meromorphic analysis of our generating functions. Our results also apply to questions about certain kinds of tilings and rhythm patterns.

  20. INTERPOLATION WITH RESTRICTED ARC LENGTH

    Institute of Scientific and Technical Information of China (English)

    Petar Petrov

    2003-01-01

    For given data (ti,yi), I= 0,1,…,n,0 = t0 <t1 <…<tn = 1we study constrained interpolation problem of Favard type inf{‖f"‖∞|f∈W2∞[0,1],f(ti)=yi,i=0,…,n,l(f;[0,1])≤l0}, wherel(f";[0,1])=∫1 0 / 1+f'2(x)dx is the arc length off in [0,1]. We prove the existence of a solution f* of the above problem, that is a quadratic spline with a second derivative f"* , which coincides with one of the constants - ‖f"*‖∞,0,‖f"*‖∞ between every two consecutive knots. Thus, we extend a result ofKarlin concerning Favard problem, to the case of restricted length interpolation.

  1. Blood Flow Restricted Exercise and Vascular Function

    Directory of Open Access Journals (Sweden)

    Masahiro Horiuchi

    2012-01-01

    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  2. Methionine restriction beyond life-span extension.

    Science.gov (United States)

    Ables, Gene P; Hens, Julie R; Nichenametla, Sailendra N

    2016-01-01

    Dietary methionine restriction (MR) extends life span across species via various intracellular regulatory mechanisms. In rodents, MR induces resistance against adiposity, improves hepatic glucose metabolism, preserves cardiac function, and reduces body size, all of which can affect the onset of age-related diseases. Recent studies have shown that MR-affected biomarkers, such as fibroblast growth factor 21, adiponectin, leptin, cystathionine β synthase, and insulin-like growth factor 1, can potentially alter physiology. The beneficial effects of MR could be explained in part by its ability to reduce mitochondrial oxidative stress. Studies have revealed that MR can reduce reactive oxygen species that damage cells and promote cancer progression. It has been demonstrated that either MR or the targeting of specific genes in the methionine cycle could induce cell apoptosis while decreasing proliferation in several cancer models. The complete mechanism underlying the actions of MR on the cell cycle during cancer has not been fully elucidated. Epigenetic mechanisms, such as methylation and noncoding RNAs, are also possible downstream effectors of MR; future studies should help to elucidate some of these mechanisms. Despite evidence that changes in dietary methionine can affect epigenetics, it remains unknown whether epigenetics is a mechanism in MR. This review summarizes research on MR and its involvement in metabolism, cancer, and epigenetics.

  3. Analyzing the Restrictive Factors of Student Practice Intention Cultivation and Countermeasure in the University History Teaching%大学历史教学中学生实践动机培养的制约因素及对策分析

    Institute of Scientific and Technical Information of China (English)

    王小丽; 肖守库; 勾正刚; 许广灵

    2012-01-01

    实践动机是实践能力的构成要素之一。大学历史教学中存在着诸多制约学生实践动机培养的因素,历史教学应从培养实践兴趣,形成实践内驱力;构建研究性课堂,激发实践成就动机;加强实践教学环节,创设实践压力场景;营造实践氛国,优化实践动机培养外部环境来构建学生实践动机培养的对策,为学生实践能力发展创造条件。%Practice intention is one of component factors of practice ability. There are many factors to restrict cultivation of practice intention in the course of history teaching. Therefore, history teaching cultivates practice intention of student from cultivating practice interest and coming into practice interior power;building up study class and arousing practice achievement intention;beefing up practice teaching segment and setting up practice pressure scene;making practice atmosphere and perfecting external environment of practice intention cultivation. These countermeasures will create advantageous conditions for student cultivating practice intention cultivation and developing practice ability.

  4. Extrauterine growth restriction: Universal problem among premature infants

    Directory of Open Access Journals (Sweden)

    Brunnella Alcantara Chagas de FREITAS

    2016-02-01

    Full Text Available ABSTRACT Objective: To analyze the growth rate of premature infants in the first weeks of life and factors associated with extrauterine growth restriction. Methods: This is a cross-sectional study of 254 premature infants in a neonatal intensive care unit conducted from January 1, 2008 to December 31, 2010. Infants who died or had malformations incompatible with life were excluded. Median weight curves according to gestational age were constructed for the first four weeks of life. The Fenton growth chart calculations provided the weight Z-scores. Extrauterine growth restriction was defined as corrected weight-for-age Z-score ≤-2. Perinatal, morbidity, and health care variables were analyzed. The Poisson regression model yielded the prevalenceratios . Associations between extrauterine growth restriction and the perinatal, morbidity, and care variables were investigated. Poisson regression controlled possible confounding factors. Results: The frequency of extrauterine growth restriction was 24.0%. Most (85.0% small-for-gestational-age infants developed extrauterine growth restriction; 55.3% of extrauterine growth restriction cases involved small-for-gestational-age infants. Premature infants with gestational age >32 weeks did not recover the median birth weight until the third week of life and had a higher frequency of small-for-gestational-age. The Z-scores of non-small-for-gestational-age infants decreased more after birth than those of small-for-gestational-age infants. extrauterine growth restriction was associated with small-for-gestational-age (PR=6.14; 95%CI=3.33-11.33;p <0.001 and time without enteral diet (PR=1.08; 95%CI=1.04-1.13; p =0.010. Conclusion: Extrauterine growth restriction occurs in premature infants of all gestational age. The participation of small-for-gestational-age and nutritional practices in its genesis is noteworthy. We suggest prospective studies of all premature infants. The implementation of best care practices

  5. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  6. Measuring Regulatory Restrictions in Logistics Services

    OpenAIRE

    Hollweg, Claire; Marn-Heong WONG

    2009-01-01

    This study measures the extent of restrictions on trade in logistics services in the ASEAN+6 economies by constructing a logistics regulatory restrictiveness index for each economy that quantifies the extent of government regulations faced by logistics service providers. This is the first study of its kind to construct a regulatory index of the entire logistics sector, which includes the main modes of international transport and customs restrictions. The indices show that large differences ex...

  7. SAMHD1: a new insight into HIV-1 restriction in myeloid cells

    OpenAIRE

    Wu Li; St Gelais Corine

    2011-01-01

    Abstract Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of a putative restriction factor. Two recent studies discovered the cellular protein SAMHD1 to be this restriction factor, demonstrating that Vpx induces proteasomal degradation of SAMHD1 and enhances HIV-1 infection in myeloid-lineage cells. SAMHD1 functions as a myeloid-cell-specific HIV-1 ...

  8. The Restriction .on Educational Quality in Rural Schools

    Institute of Scientific and Technical Information of China (English)

    艾丽娜

    2012-01-01

    In order to understand the educational quality in rural schools, I went deep into Huangjia Middle School( situated in Northern China) to make the research. In this article, I focus on the restrictions on educational qualitys, which is one of the main themes about rural education. The factors influencing quality in rural schools are analyzed in this article .It is concluded that educational quality depends on the relationship of teaching and learning and its supporting context.

  9. Estimation of average causal effect using the restricted mean residual lifetime as effect measure

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben

    2016-01-01

    with respect to their survival times. In observational studies where the factor of interest is not randomized, covariate adjustment is needed to take into account imbalances in confounding factors. In this article, we develop an estimator for the average causal treatment difference using the restricted mean......Although mean residual lifetime is often of interest in biomedical studies, restricted mean residual lifetime must be considered in order to accommodate censoring. Differences in the restricted mean residual lifetime can be used as an appropriate quantity for comparing different treatment groups...

  10. 40 CFR 1033.740 - Credit restrictions.

    Science.gov (United States)

    2010-07-01

    ... restrictions. Use of emission credits generated under this part 1033 or 40 CFR part 92 is restricted depending on the standards against which they were generated. (a) Credits from 40 CFR part 92. NOX and PM credits generated under 40 CFR part 92 may be used under this part in the same manner as NOX and...

  11. Restricting mutualistic partners to enforce trade reliance

    Science.gov (United States)

    Wyatt, Gregory A. K.; Kiers, E. Toby; Gardner, Andy; West, Stuart A.

    2016-01-01

    Mutualisms are cooperative interactions between members of different species, often involving the trade of resources. Here, we suggest that otherwise-cooperative mutualists might be able to gain a benefit from actively restricting their partners' ability to obtain resources directly, hampering the ability of the restricted partner to survive and/or reproduce without the help of the restricting mutualist. We show that (i) restriction can be favoured when it makes the resources of the restricting individual more valuable to their partner, and thus allows them to receive more favourable terms of trade; (ii) restriction maintains cooperation in conditions where cooperative behaviour would otherwise collapse; and (iii) restriction can lead to either an increase or decrease in a restricted individual's fitness. We discuss the applicability of this scenario to mutualisms such as those between plants and mycorrhizal fungi. These results identify a novel conflict in mutualisms as well as several public goods dilemmas, but also demonstrate how conflict can help maintain cooperation. PMID:26813888

  12. 44 CFR 402.2 - Restricted commodities.

    Science.gov (United States)

    2010-10-01

    ... Positive List (15 CFR part 399) (as amended from time to time) of the Comprehensive Export Schedule of the... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Restricted commodities. 402.2... SHIPMENTS ON AMERICAN FLAG SHIPS AND AIRCRAFT (T-1, INT. 1) § 402.2 Restricted commodities. The...

  13. 50 CFR 648.25 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession restrictions. 648.25 Section 648.25 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... Atlantic Mackerel, Squid, and Butterfish Fisheries § 648.25 Possession restrictions. (a) Atlantic...

  14. 50 CFR 648.105 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession restrictions. 648.105 Section... Summer Flounder Fisheries § 648.105 Possession restrictions. (a) Unless otherwise specified pursuant to... for a summer flounder moratorium permit are subject to this possession limit. The owner, operator,...

  15. 50 CFR 648.164 - Possession restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession restrictions. 648.164 Section... Atlantic Bluefish Fishery § 648.164 Possession restrictions. (a) No person shall possess more than 15... is not issued a bluefish commercial permit are subject to this possession limit. The owner,...

  16. Smoking restrictions in private workplaces in Singapore.

    Science.gov (United States)

    Koh, Y H; Voo, Y O; Yong, L S

    1994-06-01

    This survey aims to determine the number and profile of private workplaces in Singapore which have a smoking restriction policy. The response rate was 43%. Of the companies which responded, 59% had some form of smoking restriction. Private companies are more likely to have a smoking restriction policy: (a) where smoking poses inherent fire risks, such as those dealing with inflammable chemicals or gases; (b) where smoking poses inherent detrimental effects to the quality of the products, such as those dealing with precision electronic microcomponents, where a smoke-free and dust-free environment is essential; (c) are larger companies; and (d) have strong management support in initiating and enforcing smoking restriction. Future programmes should give more emphasis to the service industries such as construction, insurance, banking and finance, and smaller companies (with fewer than 100 employees). They should involve the management who play an important role in implementing smoking restriction at their workplace. PMID:7997897

  17. Near BPS skyrmions and restricted harmonic maps

    Science.gov (United States)

    Speight, J. M.

    2015-06-01

    Motivated by a class of near BPS Skyrme models introduced by Adam, Sánchez-Guillén and Wereszczyński, the following variant of the harmonic map problem is introduced: a map φ :(M, g) →(N, h) between Riemannian manifolds is restricted harmonic if it locally extremizes E2 on its SDiff(M) orbit, where SDiff(M) denotes the group of volume preserving diffeomorphisms of (M, g), and E2 denotes the Dirichlet energy. It is conjectured that near BPS skyrmions tend to restricted harmonic maps in the BPS limit. It is shown that φ is restricted harmonic if and only if φ∗ h has exact divergence, and a linear stability theory of restricted harmonic maps is developed, from which it follows that all weakly conformal maps are stable restricted harmonic. Examples of restricted harmonic maps in every degree class R3 → SU(2) and R2 →S2 are constructed. It is shown that the axially symmetric BPS skyrmions on which all previous analytic studies of near BPS Skyrme models have been based, are not restricted harmonic, casting doubt on the phenomenological predictions of such studies. The problem of minimizing E2 for φ :Rk → N over all linear volume preserving diffeomorphisms is solved explicitly, and a deformed axially symmetric family of Skyrme fields constructed which are candidates for approximate near BPS skyrmions at low baryon number. The notion of restricted harmonicity is generalized to restricted F-criticality where F is any functional on maps (M, g) →(N, h) which is, in a precise sense, geometrically natural. The case where F is a linear combination of E2 and E4, the usual Skyrme term, is studied in detail, and it is shown that inverse stereographic projection R3 →S3 ≡ SU(2) is stable restricted F-critical for every such F.

  18. 中国实施国际船舶登记制度的制约因素及未来的对策%Study on the Main Restricting Factors and Countermeasures in the Future for Implementation of the International Ship Registration System in China

    Institute of Scientific and Technical Information of China (English)

    陈继红; 刘巽良; 万征; 何新华

    2014-01-01

    China’s ship flagging out problem has brought negative influence to the international shipping industry in our country, our government and industry are making effort to solve the problem. Based on the analysis of the international ship registration system policy background, this paper conducts an in-depth study of the factors restricting the implementation of the international ship registration system in China, combining with the actual situation in China in the field of industrial and commercial management, government supervision and service, the tax system and the ship finance and legal environment. In view of these factors, future countermeasures for implementation in our country and international ship registration management system are studied, which is significant to China's future ship management policy.%中资船舶海外移籍问题给我国国际航运业带来负面影响,政府及业界均在探索解决这一问题。在分析国际船舶登记制度的政策背景的基础上,结合中国实际情况从工商管理、政府行业监管和服务、税务制度以及船舶融资与法律环境等问题对我国实施国际船舶登记制度面临的制约因素进行研究,在此基础上提出我国未来实施这项制度的相关对策,这对我国未来的船舶管理政策走向有重要借鉴意义。

  19. 胰岛素样生长因子Ⅰ受体基因突变与宫内生长受限的研究进展%Development of mutation of insulin-like growth factor Ⅰreceptor and intrauterine growth restriction

    Institute of Scientific and Technical Information of China (English)

    唐梅; 杨凡

    2016-01-01

    目前有关胰岛素生长因子(IGF)家族与胎儿宫内生长受限(IUGR)的研究逐渐增多。在胰岛素样生长因子Ⅰ受体(IGF-ⅠR)基因突变所致 IUGR 患儿中,除了常见的体格生长发育落后,还常合并头小畸形,以及运动、语言发育落后等不同程度的精神发育迟滞。关于 IUGR 发生机制有较多研究,但其确切机制目前尚未明确。目前有关IGF-ⅠR 不同位点的杂合突变导致 IUGR 的研究较多,本文就IGF-ⅠR 不同位点基因突变导致的 IUGR 临床表现及其可能机制进行综述。%In recently years,the amount of researches about relationship between insulin-like growth factor(IGF)family and intrauterine growth restriction(IUGR)was increasing.IUGR which caused by insulin-like growth factor-Ⅰ receptor (IGF-Ⅰ R )mutation usually can lead to mental retardation,such as microcephaly abnormal development in motor and language besides physical growth backwardness.The mechanism of IUGR is still not clear.Now many researches focus on different point heterozygous mutation of IGF-ⅠR which leads to IUGR,and this review will make a summary of the different point mutations.

  20. Evidence for selection at HIV host susceptibility genes in a West Central African human population

    Directory of Open Access Journals (Sweden)

    Zhao Kai

    2012-12-01

    Full Text Available Abstract Background HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes that carries strains of SIV ancestral to HIV-1. Results SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding. Conclusions We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our

  1. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

    Directory of Open Access Journals (Sweden)

    I-Chueh Huang

    Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

  2. Restriction beyond the restriction point: mitogen requirement for G2 passage

    Directory of Open Access Journals (Sweden)

    te Riele Hein

    2006-05-01

    Full Text Available Abstract Cell proliferation is dependent on mitogenic signalling. When absent, normal cells cannot pass the G1 restriction point, resulting in cell cycle arrest. Passage through the G1 restriction point involves inactivation of the retinoblastoma protein family. Consequently, loss of the retinoblastoma protein family leads to loss of the G1 restriction point. Recent work in our lab has revealed that cells possess yet another mechanism that restricts proliferation in the absence of mitogens: arrest in the G2 phase of the cell cycle. Here, we discuss the similarities and differences between these restriction points and the roles of cyclin-dependent kinase inhibitors (CKIs herein.

  3. Urban water restrictions: Attitudes and avoidance

    Science.gov (United States)

    Cooper, Bethany; Burton, Michael; Crase, Lin

    2011-12-01

    In most urban cities across Australia, water restrictions remain the dominant policy mechanism to restrict urban water consumption. The extensive adoption of water restrictions as a means to limit demand, over several years, means that Australian urban water prices have consistently not reflected the opportunity cost of water. Given the generally strong political support for water restrictions and the likelihood that they will persist for some time, there is value in understanding households' attitudes in this context. More specifically, identifying the welfare gains associated with avoiding urban water restrictions entirely would be a nontrivial contribution to our knowledge and offer insights into the benefits of alternative policy responses. This paper describes the results from a contingent valuation study that investigates consumers' willingness to pay to avoid urban water restrictions. Importantly, the research also investigates the influence of cognitive and exogenous dimensions on the utility gain associated with avoiding water restrictions. The results provide insights into the impact of the current policy mechanism on economic welfare.

  4. Analysis of Restrictive Environments in the South-West Oltenia Development Region

    Directory of Open Access Journals (Sweden)

    Radu Matei Cocheci

    2016-12-01

    Full Text Available Restrictive environments can be defined as an area within a territorial system where development is constrained either by natural factors or anthropogenic factors. This paper aims to identify restrictive environments through multi-criteria analysis of Romania’s South West Oltenia development region, known for its issues regarding open-pit mining, desertification or flood risk. In order to achieve this, I proposed a typology of restrictive environments, based on an extensive literature review of natural and anthropogenic factors that can limit development. For each of the ten environmental restrictiveness types identified, several criteria were proposed, which were then weighted as a result of a questionnaire addressed to experts in the field of territorial planning. Based on the questionnaire results, an index of environmental restrictiveness is computed at LAU 2 level for the entire South-West Oltenia development region. The territorialized index highlights the environmental restrictiveness of areas susceptible to flood risk (e.g. along the Jiu valley, but also the problems faced by mining areas (Motru-Rovinari or isolated mountain areas. The computed index represents a first step towards the definition of potential inter-communal cooperation structures, that could become the object of territorial planning instruments aimed at mitigating restrictive environments.

  5. Restrictive extraocular myopathy: A presenting feature of acromegaly

    Directory of Open Access Journals (Sweden)

    Steven Heireman

    2011-01-01

    Full Text Available A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.

  6. Some restrictions on the existence of second order limit language

    Science.gov (United States)

    Ahmad, Muhammad Azrin; Sarmin, Nor Haniza; Yusof, Yuhani; Fong, Wan Heng

    2015-10-01

    The cut and paste phenomenon on DNA molecules with the presence of restriction enzyme and appropriate ligase has led to the formalism of mathematical modelling of splicing system. A type of splicing system named Yusof-Goode splicing system is used to present the transparent behaviour of the DNA splicing process. The limit language that is defined as the leftover molecules after the system reaches its equilibrium point has been extended to a second order limit language. The non-existence of the second order limit language biologically has lead to this study by using mathematical approach. In this paper, the factors that restrict the formation of the second order limit language are discussed and are presented as lemmas and theorem using Y-G approach. In addition, the discussion focuses on Yusof- Goode splicing system with at most two initial strings and two rules with one cutting site and palindromic crossing site and recognition sites.

  7. Age-restricted housing in New England

    OpenAIRE

    Peter Francese

    2008-01-01

    Fair Housing Act amendments exempt housing restricted to “older persons” from provisions protecting families with children from discrimination. But municipal leaders who believe that promoting over-55 housing will reduce education costs are in for a rude awakening.

  8. Avoidant/Restrictive Food Intake Disorder

    Science.gov (United States)

    ... Intake Disorder Binge Eating Disorder Bulimia Nervosa Pica Rumination Disorder Avoidant/restrictive food intake disorder is characterized ... Intake Disorder Binge Eating Disorder Bulimia Nervosa Pica Rumination Disorder NOTE: This is the Consumer Version. CONSUMERS: ...

  9. The Frattini Subalgebra of Restricted Lie Superalgebras

    Institute of Scientific and Technical Information of China (English)

    Liang Yun CHEN; Dao Ji MENG; Yong Zheng ZHANG

    2006-01-01

    In the present paper, we study the Frattini subalgebra of a restricted Lie superalgebra (L, [p]). We show first that if L = A1 (⊙) A2 (⊙) … (⊙) An, then φp (L) = φp (A1) + φp (A2) +… +φp (An),where each Ai is a p-ideal of L. We then obtain two results: F(L) = φ(L) = J(L) = L(1) if and only if L is nilpotent; Fp(L) and F(L) are nilpotent ideals of L if L is solvable. In addition, necessary and sufficient conditions are found for φp-free restricted Lie superalgebras. Finally, we discuss the relationships of E-p-restricted Lie superalgebras and E-restricted Lie superalgebras.

  10. Bound on m-restricted Edge Connectivity

    Institute of Scientific and Technical Information of China (English)

    Jian-ping Ou; Fu-ji Zhang

    2003-01-01

    An m-restricted edge cut is an edge cut that separates a connected graph into a disconnected one with no components having order less than m. m-restricted edge connectivity λm is the cardinality of a minimum m-restricted edge cut. Let G be a connected k-regular graph of order at least 2m that contains m-restricted edge cuts and X be a subgraph of G. Let( )(X) denote the number of edges with one end in X and the other not in X and ξm = min{( )(X): X is a connected vertex-induced subgraph of order m}. It is proved in this paper that if G has girth at least m/2 + 2, then λm ≤ξm. The upper bound of λm is sharp.

  11. Restrictions on Database Use: Are They Necessary?

    Science.gov (United States)

    Molster, H. C.

    1979-01-01

    Discusses restrictions regarding use of bibliographic data bases, cites their rationale in terms of cooperation in input creation, economics and administrative control, and notes their effect on use. (Author/CWM)

  12. Restriction/modification polypeptides, polynucleotides, and methods

    Energy Technology Data Exchange (ETDEWEB)

    Westpheling, Janet; Chung, DaeHwan; Huddleston, Jennifer; Farkas, Joel A

    2015-02-24

    The present invention relates to the discovery of a novel restriction/modification system in Caldicellulosiruptor bescii. The discovered restriction enzyme is a HaeIII-like restriction enzyme that possesses a thermophilic activity profile. The restriction/modification system also includes a methyltransferase, M.CbeI, that methylates at least one cytosine residue in the CbeI recognition sequence to m.sup.4C. Thus, the invention provides, in various aspects, isolated CbeI or M.CbeI polypeptides, or biologically active fragments thereof; isolated polynucleotides that encode the CbeI or M.CbeI polypeptides or biologically active fragments thereof, including expression vectors that include such polynucleotide sequences; methods of digesting DNA using a CbeI polypeptide; methods of treating a DNA molecule using a M.CbeI polypeptide; and methods of transforming a Caldicellulosiruptor cell.

  13. Crowding during restricted and free viewing.

    Science.gov (United States)

    Wallace, Julian M; Chiu, Michael K; Nandy, Anirvan S; Tjan, Bosco S

    2013-05-24

    Crowding impairs the perception of form in peripheral vision. It is likely to be a key limiting factor of form vision in patients without central vision. Crowding has been extensively studied in normally sighted individuals, typically with a stimulus duration of a few hundred milliseconds to avoid eye movements. These restricted testing conditions do not reflect the natural behavior of a patient with central field loss. Could unlimited stimulus duration and unrestricted eye movements change the properties of crowding in any fundamental way? We studied letter identification in the peripheral vision of normally sighted observers in three conditions: (i) a fixation condition with a brief stimulus presentation of 250 ms, (ii) another fixation condition but with an unlimited viewing time, and (iii) an unrestricted eye movement condition with an artificial central scotoma and an unlimited viewing time. In all conditions, contrast thresholds were measured as a function of target-to-flanker spacing, from which we estimated the spatial extent of crowding in terms of critical spacing. We found that presentation duration beyond 250 ms had little effect on critical spacing with stable gaze. With unrestricted eye movements and a simulated central scotoma, we found a large variability in critical spacing across observers, but more importantly, the variability in critical spacing was well correlated with the variability in target eccentricity. Our results assure that the large body of findings on crowding made with briefly presented stimuli remains relevant to conditions where viewing time is unconstrained. Our results further suggest that impaired oculomotor control associated with central vision loss can confound peripheral form vision beyond the limits imposed by crowding.

  14. Behavioral and Physiological Consequences of Sleep Restriction

    OpenAIRE

    Banks, Siobhan; Dinges, David F.

    2007-01-01

    Adequate sleep is essential for general healthy functioning. This paper reviews recent research on the effects of chronic sleep restriction on neurobehavioral and physiological functioning and discusses implications for health and lifestyle. Restricting sleep below an individual's optimal time in bed (TIB) can cause a range of neurobehavioral deficits, including lapses of attention, slowed working memory, reduced cognitive throughput, depressed mood, and perseveration of thought. Neurobehavio...

  15. Public Investment, Revenue Shocks, and Borrowing Restrictions

    OpenAIRE

    Büttner, Thiess; David E. Wildasin

    2010-01-01

    This paper lays out a theory of taxation and public investment in an intertemporal setting under conditions of revenue shocks. Without borrowing restrictions, the optimal policy is characterized by smooth time paths of taxes and public investment. While the introduction of formal borrowing restrictions leads to some precautionary savings, it gives rise to fluctuations in public investment in response to adverse but also favorable revenue shocks. This theoretical result is tested empirically u...

  16. Placental Nutrient Transport and Intrauterine Growth Restriction

    OpenAIRE

    Gaccioli, Francesca; Lager, Susanne

    2016-01-01

    Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and...

  17. Feed restriction in broiler chickens production

    OpenAIRE

    Sahraei M.

    2012-01-01

    The feed restriction program is on of the main techniques in growth curve manipulation for increasing production efficiency in broiler chicken. Quantities and qualitative feed restriction are procedures that can be used to manipulate the feeding strategies of poultry in order to decrease growth and metabolic rate to some extent and so alleviate the incidence of some metabolic diseases such as ascites, lameness, mortality, and sudden death syndrome and so im...

  18. Date restricted queries in web search engines

    OpenAIRE

    Lewandowski, Dirk

    2004-01-01

    Search engines usually offer a date restricted search on their advanced search pages. But determining the actual update of a web page is not without problems. We conduct a study testing date restricted queries on the search engines Google, Teoma and Yahoo!. We find that these searches fail to work properly in the examined engines. We discuss implications of this for further research and search engine development.

  19. Restricted three body problems at the nanoscale

    OpenAIRE

    Chan, Yue; Thamwattana, Ngamta; Hill, James M.

    2009-01-01

    In this paper, we investigate some of the classical restricted three body problems at the nanoscale, such as the circular planar restricted problem for three C60 fullerenes, and a carbon atom and two C60 fullerenes. We model the van der Waals forces between the fullerenes by the Lennard-Jones potential. In particular, the pairwise potential energies between the carbon atoms on the fullerenes are approximated by the continuous approach, so that the total molecular energy between two fullerenes...

  20. Temporary Tariffs and Capital Market Restrictions

    OpenAIRE

    Saqib Jafarey; Sajal Lahiri

    2004-01-01

    We develop a two-period model with endogenous investment and credit flows. Credit is subject to quantitative restrictions. With an exogenous restriction, we analyze the welfare effects of temporary tariffs. We then consider three scenarios under which a monopoly lender optimally decides the level of credit and a borrower country chooses an import tariff: one in which the two parties act simultaneously and two scenarios where one of them has a first-mover advantage. The equilibrium under the l...

  1. 孕妇抗磷脂抗体、胰岛素样生长因子-I与胎儿生长受限的相关性研究%Correlation study of pregnant women's antiphospholipid antibody and insulin-like growth factor I and fetal growth restriction

    Institute of Scientific and Technical Information of China (English)

    班正贺; 黎丽嫦; 翁碧艳

    2014-01-01

    Objective To investigate the relationship between the pregnant women's expression levels of anti-cardiolipin antibody (ACA) and placental tissue insulin-like growth factor-1 (IGF-I)and their role in fetal growth restriction (FGR). Methods The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum ACA-IgG and IgM of 63 pregnant women with normal full-term pregnancy (control group)and 63 patients with fetal growth restriction(study group);The immunohistochemical method and multimedia color pathological image analysis technique were used to measure the IGF-I expression level in placenta tissues. Results The positive rate of ACA in the study group was 19.0% and that in the control group was 3.2%,with significant difference between the two groups(P 0.05),but were significantly different in placenta weight and fetal body weight (P < 0.05). Conclusion Positive serum ACA or decreased IGF-I expression levels in placenta tissues of the pregnant women is one of the risk factors of FGR.Whether ACA can decrease the IGF-I expression level in placenta tissues needs further study.%目的:探讨胎儿生长受限(FGR)孕妇抗心磷脂抗体(ACA)与胎盘组织胰岛素样生长因子-I(IGF-I)表达水平间的关系及两者在FGR发生中的作用。方法采用酶联免疫吸附法(ELISA法)测定63例正常足月妊娠孕妇(对照组)及63例胎儿生长受限孕妇(研究组)血清中ACA-IgG、IgM;利用免疫组织化学方法及多媒体彩色病理图像分析技术测定胎盘组织IGF-I表达水平。结果研究组抗心磷脂抗体阳性率为19.0%,对照组为3.2%,两组比较,有显著性差异(P<0.05);研究组胎盘组织IGF-1表达水平明显低于对照组(P<0.05);ACA阳性组与ACA阴性组两组比较,胎盘组织IGF-I表达水平无显著差异(P>0.05),胎盘重量、胎儿体重有显著差异(P<0.05)。结论孕妇血清ACA阳性或胎盘组织IGF-I表达水平下降是导致FGR

  2. Emotion regulation training to reduce problematic dietary restriction: An experimental analysis.

    Science.gov (United States)

    Haynos, Ann F; Hill, Bailey; Fruzzetti, Alan E

    2016-08-01

    Evidence suggests that emotion regulation may be a process relevant to problematic dietary restriction. However, emotion regulation has not been evaluated as an intervention target across a range of restriction severity. This study utilized an experimental design to examine whether targeting emotion regulation reduced problematic dietary restriction. Within a self-identified restrictive sample (n = 72), the effects of an emotion regulation condition (i.e., emotion regulation training) were compared to those of a control condition (i.e., nutrition information training) on dietary restriction indices (i.e., effort to reduce intake on a progressive ratio task, work towards an alternate reinforcer on a progressive ratio task, intake by dietary recall) following a stressor. Exploratory analyses of potential moderators (i.e., restraint, BMI, binge eating and purging status, emotion regulation difficulties) were conducted to examine whether these factors affected the impact of training on dietary restriction. No significant main effects of condition were detected on any outcome measure. However, results were moderated by BMI status. Participants with lower BMIs exerted less effort towards dietary restriction following the emotion regulation condition versus the control condition (p = 0.02). Results suggest that targeting emotion regulation may help to reduce problematic dietary restriction among lower weight individuals. PMID:27105583

  3. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction*

    Institute of Scientific and Technical Information of China (English)

    Jing Liu; Xiaofeng Wang; Ying Liu; Na Yang; Jing Xu; Xiaotun Ren

    2013-01-01

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neo-natal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cel s in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cel apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cel line-derived neuro-trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cel apoptosis through the glial cel line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  4. Protein Expressions and Their Immunogenicity from Riemerella anatipestifer Cultured in Iron Restriction Medium

    OpenAIRE

    Yifei Yang; Changqin Gu; Yonghong Liao; Qingping Luo; Xueying Hu; Wanpo Zhang; Huabin Shao; Guofu Cheng

    2013-01-01

    Riemerella anatipestifer was cultured in both iron restriction media and normal media. Two-dimensional gel electrophoresis identified 23 proteins that significantly increased in the iron restriction media. Of them 12 proteins were analyzed with mass spectrography. Nine of 12 proteins belong to 6 different protein families: fibronectin type iii domain protein, secreted subtilase family protein, phosphoglycerate kinase, translation elongation factor, leucine-rich repeat-containing protein, and ...

  5. Cytosine methylation dysregulation in neonates following intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Francine Einstein

    Full Text Available BACKGROUND: Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM, manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR and control subjects. METHODS AND FINDINGS: Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. CONCLUSIONS: Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

  6. Fasting and Caloric Restriction in Cancer Prevention and Treatment.

    Science.gov (United States)

    Brandhorst, Sebastian; Longo, Valter D

    2016-01-01

    Cancer is the second leading cause of death in the USA and among the leading major diseases in the world. It is anticipated to continue to increase because of the growth of the aging population and prevalence of risk factors such as obesity, smoking, and/or poor dietary habits. Cancer treatment has remained relatively similar during the past 30 years with chemotherapy and/or radiotherapy in combination with surgery remaining the standard therapies although novel therapies are slowly replacing or complementing the standard ones. According to the American Cancer Society, the dietary recommendation for cancer patients receiving chemotherapy is to increase calorie and protein intake. In addition, there are no clear guidelines on the type of nutrition that could have a major impact on cancer incidence. Yet, various forms of reduced caloric intake such as calorie restriction (CR) or fasting demonstrate a wide range of beneficial effects able to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories are emerging as interventions with the potential to be widely used to prevent and treat cancer. Here, we review preclinical and preliminary clinical studies on dietary restriction and fasting and their role in inducing cellular protection and chemotherapy resistance.

  7. Fasting and Caloric Restriction in Cancer Prevention and Treatment.

    Science.gov (United States)

    Brandhorst, Sebastian; Longo, Valter D

    2016-01-01

    Cancer is the second leading cause of death in the USA and among the leading major diseases in the world. It is anticipated to continue to increase because of the growth of the aging population and prevalence of risk factors such as obesity, smoking, and/or poor dietary habits. Cancer treatment has remained relatively similar during the past 30 years with chemotherapy and/or radiotherapy in combination with surgery remaining the standard therapies although novel therapies are slowly replacing or complementing the standard ones. According to the American Cancer Society, the dietary recommendation for cancer patients receiving chemotherapy is to increase calorie and protein intake. In addition, there are no clear guidelines on the type of nutrition that could have a major impact on cancer incidence. Yet, various forms of reduced caloric intake such as calorie restriction (CR) or fasting demonstrate a wide range of beneficial effects able to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories are emerging as interventions with the potential to be widely used to prevent and treat cancer. Here, we review preclinical and preliminary clinical studies on dietary restriction and fasting and their role in inducing cellular protection and chemotherapy resistance. PMID:27557543

  8. A randomized trial of dietary sodium restriction in CKD.

    Science.gov (United States)

    McMahon, Emma J; Bauer, Judith D; Hawley, Carmel M; Isbel, Nicole M; Stowasser, Michael; Johnson, David W; Campbell, Katrina L

    2013-12-01

    There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3-4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.

  9. Characterization of RNA binding and chaperoning activities of HIV-1 Vif protein: Importance of the C-terminal unstructured tail

    OpenAIRE

    Sleiman, Dona; Bernacchi, Serena; Xavier Guerrero, Santiago; Brachet, Franck; Larue, Valéry; Paillart, Jean-Christophe; Tisné, Carine

    2014-01-01

    The viral infectivity factor (Vif) is essential for the productive infection and dissemination of HIV-1 in non-permissive cells, containing the cellular anti-HIV defense cytosine deaminases APOBEC3 (A3G and A3F). Vif neutralizes the antiviral activities of the APOBEC3G/F by diverse mechanisms including their degradation through the ubiquitin/proteasome pathway and their translational inhibition. In addition, Vif appears to be an active partner of the late steps of viral replication by interac...

  10. Potentializing and restrictive factors in the implementation of the balanced scorecard: a study in a contruction firm in the state of Ceará Fatores potencializadores e restritivos à implantação do Balanced Scorecard:um estudo em uma empresa de construção civil do Ceará

    Directory of Open Access Journals (Sweden)

    Roberta Catrib de Azevedo Lemos

    2011-12-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The Balanced Scorecard (BSC, better known as a method to translate a firm’s mission and strategy into a broad set of performance measurements, has been used for the strategic management of organizations, serving as a measurement system  that, besides the financial goals, includes performance characteristics. This research, which was carried out through a case study, aims at identifying the main potentializing and restrictive factors in the implementation of the BSC in a civil construction firm in the state of Ceará, the Porto Freire Engineering. The bibliographical research, which was based on the managerial reports of the 2003 to 2009 period, showed that the firm conducted the process necessary to the implementation of the BSC for the management of its strategy. The field data were collected through questionnaires and interviews applied, respectively, to the employees and managers who already were in the firm when the BSC was implemented. The questionnaire data show that, among the set of twenty factors considered in the research, only three were deemed potentializing in the implementation of the BSC: technical support, balancing of the four perspectives and preservation of

  11. Optimal control of entanglement under restrictions

    Energy Technology Data Exchange (ETDEWEB)

    Haeberle, Thomas Stefan; Freyberger, Matthias [Institut fuer Quantenphysik, Universitaet Ulm, D-89069 Ulm (Germany)

    2013-07-01

    We present a novel iterative algorithm with a special presearching step that can optimize the entanglement of a coupled quantum system while fulfilling restrictions of the control function. As an example we regard two atoms in a harmonic trap which interact via point-like collisions. Our aim is to improve the entanglement at a fixed time by dynamically varying the trap frequency within a fixed interval. In order to get rid of the restrictions for the trap frequency, we use a suitable parameterization that transforms the optimization problem from a restricted to an unrestricted one. By applying the pre-searching step we get a reasonable initial guess for the optimal trap frequency. Finally, we use a standard method based on optimal control theory to further increase the entanglement.

  12. Risk Factors for Eating Disorders

    Science.gov (United States)

    Striegel-Moore, Ruth H.; Bulik, Cynthia M.

    2007-01-01

    The authors review research on risk factors for eating disorders, restricting their focus to studies in which clear precedence of the hypothesized risk factor over onset of the disorder is established. They illustrate how studies of sociocultural risk factors and biological factors have progressed on parallel tracks and propose that major advances…

  13. Quantum Game with Restricted Matrix Strategies

    Institute of Scientific and Technical Information of China (English)

    CHENBo; MAYing-Jun; LONGGui-Lu

    2003-01-01

    We study a quantum game played by two players with restricted multiple strategies. It is found that in this restricted quantum game Nash equilibrium does not always exist when the initial state is entangled. At the same time,we find that when Nasli equilibrium exists the payoff function is usually different from that in the classical counterpart except in some special cases. This presents an explicit example showing quantum game and classical game may differ.When designing a quantum game with limited strategies, the allowed strategy should be carefully chosen according to the type of initial state.

  14. Quantum Game with Restricted Matrix Strategies

    Institute of Scientific and Technical Information of China (English)

    CHEN Bo; MA Ying-Jun; LONG Gui-Lu

    2003-01-01

    We study a quantum game played by two players with restricted multiple strategies. It is found that in this restricted quantum game Nash equilibrium does not always exist when the initial state is entangled. At the same time,we find that when Nash equilibrium exists the payoff function is usually different from that in the classical counterpart except in some special cases. This presents an explicit example showing quantum game and classical game may differ.When designing a quantum game with limited strategies, the allowed strategy should be carefully chosen according to the type of initial state.

  15. Methylation of insulin-like growth factor binding protein 3 gene in neonates with intrauterine growth restriction%胰岛素样生长因子结合蛋白3在宫内生长受限儿中的甲基化研究

    Institute of Scientific and Technical Information of China (English)

    苏爱玲; 蒋犁; 葛芹玉

    2011-01-01

    Objective To study the role of promoter methylation of insulin-like growth factor binding protein 3 (ICFBP3) in intrauterine growth restriction (IUGR). Methods Fifty neonates with IUCR and 30 healthy neonates were enrolled. The promoter methylation status of 1GFBP3 in peripheral blood was evaluated by methylation-specific PCR (MSP) and high resolution melting (HRM) techniques. Results The complete methylation rate, partial methylation rate and non-methylation rate of IGFBP3 promoter in the IUGR group was 4% (2/50) , 40% (20/50) and 56% (28/50) , respectively. The partial methylation rate and non-methylation rate of IGFBP3 promoter in the control group were 13% (4/30) and 87% (26/30) , respectively. There were significant differences in the promoter methylation rate of IGFBP3 between the two groups ( P < 0. 01 ). Conclusions The promoter methylation of IGFBP3 gene is associated with the pathogenesis of IUGR.%目的 探讨胰岛素样生长因子结合蛋白3(IGFBP3)启动子区甲基化状态在胎儿宫内生长受限(IUGR)中的作用.方法 选取IUGR新生儿50例及正常新生儿30例,应用甲基化特异性PCR(MSP)及高分辨率溶解(HRM)技术检测外周血中IGFBP3基因的甲基化状态.结果 IUGR组中IGFBP3启动子区完全甲基化比例为4%(2/50),部分甲基化比例为40%(20/50),未甲基化比例为56%(28/50);对照组中部分甲基化比例为13%(4/30),未甲基化比例为87%(26/30),两组甲基化率差异有统计学意义(P<0.01).结论 IGFBP3基因启动子区的甲基化程度与IUGR的发生有关.

  16. 早产儿发生呼吸窘迫综合征及患儿宫外发育迟缓的相关因素分析%Analysis on the relevant factors of respiratory distress syndrome and ex-trauterine growth restriction for premature infants

    Institute of Scientific and Technical Information of China (English)

    项俊华; 夏红卫

    2015-01-01

    Objective To analyze the relevant factors of respiratory distress syndrome for premature infants and the risk factors of extrauterine growth restriction(EUGR)for the premature infants with respiratory distress syndrome. Methods All 153 premature infants with respiratory distress syndrome were selected as case group, and they were assigned to EUGR group and non-EUGR group on the basis of whether they had EUGR. 200 premature infants without respiratory distress syndrome were selected as control group during the same period. Clinical data of each group were observed and relevant factors were analyzed. Results Differences of incidence rates of EUGR and severe EUGR between the pre-mature infants with respiratory distress syndrome and those without respiratory distress syndrome were statistically sig-nificant (P<0.05). Incidence rates of gestational age, birth weight, multiple pregnancy rate, preventive application rate of PS,antenatal application rate of hormone,fetal distress or asphyxia,amniotic fluid aspiration,intrauterine in-fection, placenta previa/placental abruption, cesarean section, pregnancy-induced hypertension and ges tational dia-betes mellitus were relevant factors of respiratory distress syndrome for premature infants (P<0.05). Gestational age of less than 31 weeks, multiple pregnancy, time reaching total enteral nutrition, feeding intolerance, and time resuming birth weight were independent risk factors of EUGR for premature patients with respiratory distress syndrome (P<0.05). Antenatal application of hormone was the protective factor of EUGR for premature infants with respiratory dis-tress syndrome (P<0.05). Conclusion Young gestational age and multiple pregnancy are common risk factors of respi-ratory distress syndrome and EUGR for premature infants, and antenatal application of hormone has protective effect on the two diseases. Respiratory distress syndrome has obvious adverse effect on infants' extrauterine growth, and EU-GR for premature infants

  17. Restricted total stability and total attractivity

    Directory of Open Access Journals (Sweden)

    Giuseppe Zappala'

    2006-08-01

    Full Text Available In this paper the new concepts of restricted total stability and total attractivity is formulated. For this purpose the classical theory of Malkin with suitable changes and the theory of limiting equations, introduced by Sell developed by Artstein and Andreev, are used. Significant examples are presented.

  18. 45 CFR 400.44 - Restriction.

    Science.gov (United States)

    2010-10-01

    ... Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Immigration Status and Identification of Refugees Documentation of Refugee Status § 400.44 Restriction. An applicant for asylum is...

  19. 9 CFR 166.2 - General restrictions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false General restrictions. 166.2 Section 166.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE SWINE HEALTH PROTECTION SWINE HEALTH PROTECTION General Provisions § 166.2 General...

  20. Material and Cultural Restriction of Political Life

    Institute of Scientific and Technical Information of China (English)

    马国祥

    2015-01-01

    Material and culture have a certain influence on the political life. In general, the higher level of economic development of the country, people's political life is more democratic. Culture has some negative effect on the political life. China's traditional cul-ture has restricted the people's political life in some ways.

  1. Restricted Liberty, Parental Choice and Homeschooling

    Science.gov (United States)

    Merry, Michael S.; Karsten, Sjoerd

    2010-01-01

    In this paper the authors carefully study the problem of liberty as it applies to school choice, and whether there ought to be restricted liberty in the case of homeschooling. They examine three prominent concerns that might be brought against homeschooling, viz., that it aggravates social inequality, worsens societal conflict and works against…

  2. Restricted liberty, parental choice and homeschooling

    NARCIS (Netherlands)

    M.S. Merry; S. Karsten

    2010-01-01

    In this paper the authors carefully study the problem of liberty as it applies to school choice, and whether there ought to be restricted liberty in the case of homeschooling. They examine three prominent concerns that might be brought against homeschooling, viz., that it aggravates social inequalit

  3. Joint Venture Structuring in Restricted Industries

    Institute of Scientific and Technical Information of China (English)

    CHRIS; DEVONSHIRE-ELLIS

    2008-01-01

    When investing in China’s restricted in- dustries, it is essential to have a joint venture (JV) partner. Often the maximum percent- age of equity allowed in foreign ownership can only be 50 percent. So what options are available to the foreign investor to mitigate the risk of not owning, on paper, a majority

  4. Observing Behavior and Atypically Restricted Stimulus Control

    Science.gov (United States)

    Dube, William V.; Dickson, Chata A.; Balsamo, Lyn M.; O'Donnell, Kristin Lombard; Tomanari, Gerson Y.; Farren, Kevin M.; Wheeler, Emily E.; McIlvane, William J.

    2010-01-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded…

  5. 12 CFR 575.11 - Operating restrictions.

    Science.gov (United States)

    2010-01-01

    ..., the reference in § 563b.510 of this chapter to five percent refers to minority shareholders. (d) Restrictions on waiver of dividends. No mutual holding company may waive its right to receive any dividend... holding company provides the OTS with written notice of its intent to waive its right to receive...

  6. Restrictive dermopathy - Report of 12 cases

    NARCIS (Netherlands)

    Smitt, JHS; van Asperen, CJ; Niessen, CM; Beemer, FA; van Essen, AJ; Hulsmans, RFHJ; Oranje, AP; Steijlen, PM; Wesby-van Swaay, E; Tamminga, P; Breslau-Siderius, EJ

    1998-01-01

    Background: This study describes 12 cases of restrictive dermopathy seen during a period of 8 years by the Dutch Task Force on Genodermatology. We present these unique consecutive cases to provide more insight into the clinical picture and pathogenesis of the disease. Observations: Clinical features

  7. 46 CFR 119.405 - Fuel restrictions.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Fuel restrictions. 119.405 Section 119.405 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150 PASSENGERS OR WITH OVERNIGHT ACCOMMODATIONS FOR MORE THAN 49 PASSENGERS MACHINERY INSTALLATION...

  8. Design implications of extremely restricted patterning

    Science.gov (United States)

    Vaidyanathan, Kaushik; Liu, Renzhi; Liebmann, Lars; Lai, Kafai; Strojwas, Andzrej J.; Pileggi, Larry

    2014-07-01

    Escalating manufacturing cost and complexity is challenging the premise of affordable scaling. With lithography accounting for a large fraction of wafer costs, researchers are actively exploring several cost-effective alternative lithographic techniques, such as directed self-assembly, self-aligned multiple patterning, etc. However, most of the alternative lithographic techniques are restrictive, and it is important to understand the impact of such pattering restrictions on system-on-chip (SoC) design. To this end, we artificially restricted all layers in a 14 nm process to be pure gratings and observed that the pure gratings approach results in an inefficient SoC design with several process integration concerns. To come up with a technology definition that is mindful of designer requirements, it is essential to undertake a holistic design technology co-optimization (DTCO) considering several SoC design elements, such as standard cell logic, static random access memory bitcells, analog blocks, and physical synthesis. Our DTCO on the IBM 14 nm process with additional 10- and 7-nm node-like pattern restrictions leads us to converge on a set of critical pattern constructs that are required for an efficient and affordable SoC design.

  9. A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.

    Directory of Open Access Journals (Sweden)

    Malene Hansen

    2008-02-01

    Full Text Available In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin. TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

  10. 7 CFR 322.28 - General requirements; restricted articles.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false General requirements; restricted articles. 322.28... EQUIPMENT Importation and Transit of Restricted Articles § 322.28 General requirements; restricted articles. (a) The following articles from any region are restricted articles: (1) Dead bees of any genus;...

  11. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anthony E Civitarese

    2007-03-01

    Full Text Available BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y, overweight (body mass index, 27.8 +/- 0.7 kg/m(2 individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX, 12.5% CR + 12.5% increased energy expenditure (EE. In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008. Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05. In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005 and 21% +/- 4% in the CREX group (p < 0.004, with no change in the control group (2% +/- 2%. However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid cycle (citrate synthase, beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase, and electron transport chain (cytochrome C oxidase II was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003 and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011, but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content

  12. Restriction of dairy products: a reality in inflammatory bowel disease patients

    Directory of Open Access Journals (Sweden)

    Mirella Brasil Lopes

    2014-03-01

    Full Text Available Introduction: Calcium deficiency is considered a risk factor for the development of osteoporosis in inflammatory bowel disease (IBD patients. Various dietary restrictions, including milk products are reported by these patients. Objective: To evaluate dairy product and dietary calcium intake by IBD patients. Methods: This cross-sectional study enrolled 65 outpatients with IBD recruited from one reference center for IBD. A semi-structured questionnaire (to collect demographic, socioeconomic and clinical data and a quantitative food frequency questionnaire were administered. With regard to clinical data, we evaluated the anthropometric nutritional status, the disease classification, the disease activity index and the presence of gastrointestinal symptoms. Selfreported modifications in the use of dairy products were evaluated. Results: The IBD patients´ ages ranged from 20-75 years and 67.0% were diagnosed with ulcerative colitis. The majority (64.7% reported restricting dairy products. The frequency of gastrointestinal symptoms was higher among the Crohn´s disease patients who restricted dairy products than among those with no restrictions (100% vs 42.9%; p = 0.013; this result was not observed among the UC (ulcerative colitis patients. Disease activity was also more frequent in the IBD patients who restricted dairy products than in those with no restrictions (23.8% vs 4.5%; p = 0.031, and among the UC patients, extensive disease was more common in the patients who restricted dairy products than in those with no restrictions (42.9% vs 20.0%; p = 0.03. Conclusion: Restricting dairy products is common among IBD patients, possibly due to disease activity, the presence of gastrointestinal symptoms and the extension of the disease.

  13. Effects of the Post-Olympics Driving Restrictions on Air Quality in Beijing

    Directory of Open Access Journals (Sweden)

    Hua Ma

    2016-09-01

    Full Text Available To reduce congestion and air pollution, 20% driving restriction, a license plate-based traffic control measure, has been implemented in Beijing since October 2008. While the long-term impacts of this policy remain controversial, it is important to understand how and why the policy effects of driving restrictions change over time. In this paper, the short- and long-run effects of the 20% driving restrictions in Beijing and the key factors shaping the effects are analyzed using daily PM10 pollution data. The results showed that in the short run, 20% driving restriction could effectively reduce ambient PM10 levels. However, this positive effect rapidly faded away within a year due to long-term behavioral responses of residents. A modified 20% restriction, designed to replace the original 20% restriction system since April 2009, which is less stringent and provides more possibility for intertemporal driving substitution, has shown some positive influence on air quality over the long run comparing with that under the original policy design. Temporarily, the more stringent the driving restriction was, the better effects it would have on air quality. In the long-run, however, the policy was likely to cause a vicious circle, and more stringent policy might induce stronger negative incentives which would result in even worse policy effects. Lessons learned from study of the effects of driving restrictions in Beijing will help other major cities in China and abroad to use driving restrictions more prudently and effectively in the future. Decision-makers should carefully consider the pros and cons of a transport policy and conduct the ex-ante and ex-post evaluations on it.

  14. An unusual ECG pattern in restrictive cardimyopathy.

    Science.gov (United States)

    Selvaganesh, M; Arul, A S; Balasubramanian, S; Ganesan, N; Naina Mohammed, S; Sivakumar, G S; Veeramani, S R; Jeyasingh, P; Sathishkumar, S; Selvaraju, S

    2015-01-01

    Restrictive cardiomyopathy is the least common type of primary cardiomyopathies. Electrocardiographic recording is abnormal in 99% of patients with RCM. Biatrial enlargement, obliquely elevated ST segment with notched or biphasic late peaking T waves are considered characteristic ECG finding. Significant ST depression with T inversion mimicking subendocardial ischemia has also been reported in patients with RCM and is even suggested as a predictor of sudden cardiac death. We noted a similar ECG pattern in a 16 yr girl with Idiopathic restrictive cardiomyopathy. Coronaries were normal, stress perfusion imaging did not show any perfusion defect. This diffuse resting ST depression with T inversion in precordial & inferior leads along with ST elevation in aVR was persistent for more than six months. PMID:26304570

  15. A Property Restriction Based Knowledge Merging Method

    Science.gov (United States)

    Che, Haiyan; Chen, Wei; Feng, Tie; Zhang, Jiachen

    Merging new instance knowledge extracted from the Web according to certain domain ontology into the knowledge base (KB for short) is essential for the knowledge management and should be processed carefully, since this may introduce redundant or contradictory knowledge, and the quality of the knowledge in the KB, which is very important for a knowledge-based system to provide users high quality services, will suffer from such "bad" knowledge. Advocates a property restriction based knowledge merging method, it can identify the equivalent instances, redundant or contradictory knowledge according to the property restrictions defined in the domain ontology and can consolidate the knowledge about equivalent instances and discard the redundancy and conflict to keep the KB compact and consistent. This knowledge merging method has been used in a semantic-based search engine project: CRAB and the effect is satisfactory.

  16. Affective tone of mothers' statements to restrict their children's eating.

    Science.gov (United States)

    Pesch, Megan H; Miller, Alison L; Appugliese, Danielle P; Rosenblum, Katherine L; Lumeng, Julie C

    2016-08-01

    Maternal restrictive feeding behaviors have been associated with child weight status. The affective tone of mothers' statements intended to restrict their children's eating has not been examined. The objectives of this study were to describe the affective tone of mothers' restrictive feeding behaviors (positive or negative), and to test the association of child and mother characteristics with rates of Restriction with Positive Affect, Restriction with Negative Affect and Total Restriction. A total of 237 low-income child-mother dyads (mean child age 5.9 years) participated in a videotaped standardized laboratory eating protocol, during which mothers and children were both presented with large servings of cupcakes. A coding scheme was developed to count each restrictive statement with a positive affective tone and each restrictive statement with a negative affective tone. To establish reliability, 20% of videos were double-coded. Demographics and anthropometrics were obtained. Poisson regression models were used to test the association between characteristics of the child and mother with counts of Restriction with Positive Affect, Restriction with Negative Affect, and Total Restriction. Higher rates of Restriction with Positive Affect and Total Restriction were predicted by child obese weight status, and mother non-Hispanic white race/ethnicity. Higher rates of Restriction with Negative Affect were predicted by older child age, child obese weight status, mother non-Hispanic white race/ethnicity, and lower mother education level. In conclusion, in this study mothers of obese (vs. non-obese) children had higher rates of restriction in general, but particularly higher rates of Restriction with Negative Affect. Rather than being told not to restrict, mothers may need guidance on how to sensitively restrict their child's intake. Future studies should consider the contributions of maternal affect to children's responses to maternal restriction. PMID:27090342

  17. Blood flow-restricted exercise in space

    OpenAIRE

    Hackney, Kyle J; Everett, Meghan; Scott, Jessica M; Ploutz-Snyder, Lori

    2012-01-01

    Prolonged exposure to microgravity results in chronic physiological adaptations including skeletal muscle atrophy, cardiovascular deconditioning, and bone demineralization. To attenuate the negative consequences of weightlessness during spaceflight missions, crewmembers perform moderate- to high-load resistance exercise in conjunction with aerobic (cycle and treadmill) exercise. Recent evidence from ground-based studies suggests that low-load blood flow-restricted (BFR) resistance exercise tr...

  18. Privacy-Preserving Restricted Boltzmann Machine

    OpenAIRE

    Yu Li; Yuan Zhang; Yue Ji

    2014-01-01

    With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM). The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provi...

  19. Free vs. Restricted Immigration: Bilateral Country Study

    OpenAIRE

    Razin, Assaf; Wahba, Jackline

    2011-01-01

    This paper tests the differential effects of the generosity of the welfare state under free migration and under policy-controlled migration, distinguishing between source developing and developed countries. We utilize free-movement within the EU to examine the free migration regime and compare that to immigration into the EU from two other groups, developed and developing source countries, to capture immigration-restricted regimes. We standardize cross-country education quality differences by...

  20. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis

    OpenAIRE

    Piccio, Laura; Stark, Jennifer L.; Cross, Anne H.

    2008-01-01

    Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic and physiologic modifications, including anti-inflammatory, antioxidant, and neuroprotective effects that may be beneficial in multiple sclerosis (MS). The present studies sought to determine whether CR or increased calorie intake alters the course of experimental autoimmune encephalomyelitis (EAE), the leading animal model for MS. SJL and C57BL/6 mice were subjected to 40% ...

  1. Restricted Conformal Property of Compressive Sensing

    OpenAIRE

    Cheng, Tao

    2014-01-01

    Energy and direction are tow basic properties of a vector. A discrete signal is a vector in nature. RIP of compressive sensing can not show the direction information of a signal but show the energy information of a signal. Hence, RIP is not complete. Orthogonal matrices can preserve angles and lengths. Preservation of length can show energies of signals like RIP do; and preservation of angle can show directions of signals. Therefore, Restricted Conformal Property (RCP) is proposed according t...

  2. Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

    Science.gov (United States)

    Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Thamotharan, Shanthie; Shin, Bo-Chul; Stout, David; Devaskar, Sherin U

    2012-06-01

    Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype. PMID:22461568

  3. Team Formation and Communication Restrictions in Collectives

    Science.gov (United States)

    Agogino, Adrian K.; Turner, Kagan

    2003-01-01

    A collective of agents often needs to maximize a "world utility" function which rates the performance of an entire system, while subject to communication restrictions among the agents. Such communication restrictions make it difficult for agents which try to pursue their own "private" utilities to take actions that also help optimize the world utility. Team formation presents a solution to this problem, where by joining other agents, an agent can significantly increase its knowledge about the environment and improve its chances of both optimizing its own utility and that its doing so will contribute to the world utility. In this article we show how utilities that have been previously shown to be effective in collectives can be modified to be more effective in domains with moderate communication restrictions resulting in performance improvements of up to 75%. Additionally we show that even severe communication constraints can be overcome by forming teams where each agent of a team shares the same utility, increasing performance an additional 25%. We show that utilities and team sizes can be manipulated to form the best compromise between how "aligned" an agent s utility is with the world utility and how easily an agent can learn that utility.

  4. Restriction endonucleases digesting DNA in PCR buffer

    Institute of Scientific and Technical Information of China (English)

    LIU Xue-dong; ZHENG Dong; ZHOU Yan-na; MAO Wei-wei; MA Jian-zhang

    2005-01-01

    Six commonly used restriction endonucleases (Res) (Acc I, Ban II, EcoR I, Hind III, Sac I, Sca I) were tested for their ability to directly digest DNA completely in the Polymerase Chain Reaction (PCR) buffers. The results showed that: with the requirement for additional magnesium supplemented as activator, Res, except EcoR I appeared star activity, completely digested unmethylated lambda DNA after overnight incubation in PCR buffer and functioned as equally well as in recommended Restriction Enzyme Buffer provided with each enzyme; all Res tested completely digested PCR products in PCR buffer, it implied digestion of PCR products may often be performed directly in the PCR tube without the requirement for any precipitation or purification steps; and the concentration of MgCl2 from 2.5 mmol·L-1 to 10 mmol·L-1 did not significantly affect activity of Res in PCR buffer. This simplified method for RE digestion of PCR products could have applications in restriction fragment length polymorphism (RFLP) analysis and single-stranded conformational polymorphism (SSCP) analysis of large PCR products. However, usage of this procedure for cloning applications needs further data.

  5. Emergency building temperature restrictions. Final evaluation

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-11-01

    On July 5, 1979, DOE promulgated final regulations of the Emergency Building Temperature Restrictions program, placing emergency restrictions on thermostat settings for space heating, space cooling, and hot water in commercial, industrial, and nonresidential public buildings. The final regulations restricted space heating to a maximum of 65/sup 0/F, hot water temperature to a maximum of 105/sup 0/F, and cooling temperature to a minimum of 78/sup 0/F. A comprehensive evaluation of the entire EBTF program for a nine-month period from July 16, 1979 is presented. In Chapter 1, an estimate of the population of buildings covered by EBTR is presented. In Chapter 2, EBTR compliance by building type and region is reported. Exemptions are also discussed. In Chapter 3, the simulations of building energy use are explained and the relative impact of various building characteristics and effectiveness of different control strategies are estimated. Finally, in Chapter 4, the methodology for scaling the individual building energy savings to the national level is described, and estimated national energy savings are presented.

  6. Food restriction modifies ultrastructure of hippocampal synapses.

    Science.gov (United States)

    Babits, Réka; Szőke, Balázs; Sótonyi, Péter; Rácz, Bence

    2016-04-01

    Consumption of high-energy diets may compromise health and may also impair cognition; these impairments have been linked to tasks that require hippocampal function. Conversely, food restriction has been shown to improve certain aspects of hippocampal function, including spatial memory and memory persistence. These diet-dependent functional changes raise the possibility that the synaptic structure underlying hippocampal function is also affected. To examine how short-term food restriction (FR) alters the synaptic structure of the hippocampus, we used quantitative electron microscopy to analyze the organization of neuropil in the CA1 stratum radiatum of the hippocampus in young rats, consequent to reduced food. While four weeks of FR did not modify the density, size, or shape of postsynaptic spines, the synapses established by these spines were altered, displaying increased mean length, and more frequent perforations of postsynaptic densities. That the number of perforated synapses (believed to be an indicator of synaptic enhancement) increased, and that the CA1 spine population had on average significantly longer PSDs suggests that synaptic efficacy of axospinous synapses also increased in the CA1. Taken together, our ultrastructural data reveal previously unrecognized structural changes at hippocampal synapses as a function of food restriction, supporting a link between metabolic balance and synaptic plasticity.

  7. 产妇血及胎盘组织转化生长因子β1异常表达与预测胎儿生长受限的研究%Study on abnormal expression of transforming growth factor-β1 in maternal blood and placenta of patients with fetal growth restriction

    Institute of Scientific and Technical Information of China (English)

    吕娜; 王桂婵; 李少君

    2011-01-01

    目的 探讨产妇血及胎盘组织转化生长因子β1(TGF-β1)表达与胎儿生长受限(FGR)的关系.方法 采用酶联免疫吸附法(ELISA)和免疫组织化学方法检测33例FGR孕妇和120例正常孕妇血及胎盘组织TGF-β1水平,比较两组孕妇血及胎盘组织TGF-β1水平变化及阳性和强阳性表达.结果 TGF-β1阳性颗粒主要表达于绒毛中的合体滋养层细胞中的胞浆,细胞滋养层细胞和绒毛间质细胞未见TGF-β1表达,而蜕膜细胞呈弱阳性表达.FGR组孕妇血清中TGF-β1水平(76.5±33.4)高于对照组(47.6±24.2,t′=4.65,P<0.05).TGF-β1在两组孕妇绒毛组织合体滋养层细胞表达阳性率为100%,但合体滋养层细胞中TGF-β1强阳性率(81.82%)高于正常妊娠组(5.83%,P<0.01),两组孕妇蜕膜细胞中TGF-β1阳性率均为100%(P>0.05).结论 胎儿生长受限与TGF-β1水平高低有关,动态监产妇血TGF-β1水平有利预测胎儿生长受限,对临床防治具有指导意义.%Objective To find out the relationship between fetal growth restriction (FGR) and transforming growth factor -β1 (TGF-β1). Methods The levels of TGF-β1 in maternal serum and placental tissue of FGR were detected with using ELISA and immunohistochemistry technique, and it was compared with those of normal term pregnancy. Results The levels of TGF-β1 in maternal serum of FGR group were significantly higher than those of normal term pregnancy (76. 5 ± 33. 4 VS 47.6 ± 24. 2, t' = 4. 65, P <0. 05). As for the intensity of the immunohistochemistry signal, TGF-β1 in syncytiotrophoblastic cells of FGR was markedly higher than that of control group (81.82% vs 5.83%, P <0. 01). Conclusions The levels of TGF-β1 are closely related with FGR.

  8. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2005-11-01

    conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

  9. Alternatives to restrictive feeding practices to promote self-regulation in childhood: a developmental perspective.

    Science.gov (United States)

    Rollins, B Y; Savage, J S; Fisher, J O; Birch, L L

    2016-10-01

    Intake of energy-dense snack foods is high among US children. Although the use of restrictive feeding practices has been shown to be counterproductive, there is very limited evidence for effective alternatives to restriction that help children moderate their intake of these foods and that facilitate the development of self-regulation in childhood. The developmental literature on parenting and child outcomes may provide insights into alternatives to restrictive feeding practices. This review paper uses a model of parental control from the child development and parenting literatures to (i) operationally define restrictive feeding practices; (ii) summarize current evidence for antecedents and effects of parental restriction use on children's eating behaviours and weight status, and (iii) highlight alternative feeding practices that may facilitate the development of children's self-regulation and moderate children's intake of palatable snack foods. We also discuss recent empirical evidence highlighting the role of child temperament and food motivation related behaviours as factors that prompt parents to use restrictive feeding practices and, yet, may increase children's dysregulated intake of forbidden foods.

  10. Universal Restrictions on Syllable Structure: Evidence From Mandarin Chinese.

    Science.gov (United States)

    Zhao, Xu; Berent, Iris

    2016-08-01

    Across languages, certain onset clusters are systematically preferred (e.g., [Formula: see text], "[Formula: see text]" indicates preference), and speakers extend these preferences even to onsets that are unattested in their language. All such demonstrations, however, come from cluster-rich languages, so the observed preferences could reflect not universal linguistic restrictions but lexical analogy. To address this possibility, here, we turn to Mandarin Chinese-a cluster-poor language. We reasoned that, if people are sensitive to the onset hierarchy, then they should repair ill-formed onsets as better-formed ones [Formula: see text]-the worse formed the onset, the more likely its repair, hence, its misidentification. Results were consistent with this hypothesis, and they obtained irrespective of participants' experience with their second language (English). Nonetheless, the effect of syllable structure was strongly modulated by phonetic cues and task demands. These findings suggest that speakers might share broad phonological restrictions, but phonetic factors play a major role in their detection. PMID:25980969

  11. Approximate Message Passing with Restricted Boltzmann Machine Priors

    CERN Document Server

    Tramel, Eric W; Krzakala, Florent

    2015-01-01

    Approximate Message Passing (AMP) has been shown to be an excellent statistical approach to signal inference and compressed sensing problem. The AMP framework provides modularity in the choice of signal prior; here we propose a hierarchical form of the Gauss-Bernouilli prior which utilizes a Restricted Boltzmann Machine (RBM) trained on the signal support to push reconstruction performance beyond that of simple iid priors for signals whose support can be well represented by a trained binary RBM. We present and analyze two methods of RBM factorization and demonstrate how these affect signal reconstruction performance within our proposed algorithm. Finally, using the MNIST handwritten digit dataset, we show experimentally that using an RBM allows AMP to approach oracle-support performance.

  12. Approximate message passing with restricted Boltzmann machine priors

    Science.gov (United States)

    Tramel, Eric W.; Drémeau, Angélique; Krzakala, Florent

    2016-07-01

    Approximate message passing (AMP) has been shown to be an excellent statistical approach to signal inference and compressed sensing problems. The AMP framework provides modularity in the choice of signal prior; here we propose a hierarchical form of the Gauss-Bernoulli prior which utilizes a restricted Boltzmann machine (RBM) trained on the signal support to push reconstruction performance beyond that of simple i.i.d. priors for signals whose support can be well represented by a trained binary RBM. We present and analyze two methods of RBM factorization and demonstrate how these affect signal reconstruction performance within our proposed algorithm. Finally, using the MNIST handwritten digit dataset, we show experimentally that using an RBM allows AMP to approach oracle-support performance.

  13. Classical simulation of restricted quantum computations

    OpenAIRE

    Nebhwani, Mrityunjaya

    2013-01-01

    Treball final de màster oficial fet en col·laboració amb Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB) i Institut de Ciències Fotòniques (ICFO) [ANGLÈS] We study restricted models of measurement-based quantum computation; and we investigate whether their output probability distributions can be sampled from efficiently on a classical computer. We find that even for non-adaptive models of MBQC, if this task were feasible then a major conjecture of computational compl...

  14. Privacy-Preserving Restricted Boltzmann Machine

    Directory of Open Access Journals (Sweden)

    Yu Li

    2014-01-01

    Full Text Available With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM. The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provide a correctness and efficiency analysis of our algorithms. The comparative experiment shows that the accuracy is very close to the original RBM model.

  15. Privacy-preserving restricted boltzmann machine.

    Science.gov (United States)

    Li, Yu; Zhang, Yuan; Ji, Yue

    2014-01-01

    With the arrival of the big data era, it is predicted that distributed data mining will lead to an information technology revolution. To motivate different institutes to collaborate with each other, the crucial issue is to eliminate their concerns regarding data privacy. In this paper, we propose a privacy-preserving method for training a restricted boltzmann machine (RBM). The RBM can be got without revealing their private data to each other when using our privacy-preserving method. We provide a correctness and efficiency analysis of our algorithms. The comparative experiment shows that the accuracy is very close to the original RBM model. PMID:25101139

  16. Restricted fish feeding reduces cod otolith opacity

    DEFF Research Database (Denmark)

    Høie, H.; Folkvord, A.; Mosegaard, Henrik;

    2008-01-01

    The purpose of this work was to examine the effect of reduced feeding and constant temperature on cod otolith opacity. Three groups of juvenile cod were given restricted food rations at different times for 4 months, resulting in depressed somatic growth. Otolith opacity was measured on pictures...... in otolith opacity were found between individual fish both within groups and between groups. In two of the three groups significantly more translucent otolith material was deposited in response to reduced feeding. Our results show that variations in feeding and hence fish growth resulted in variation...

  17. The Monetary Policy – Restrictive or Expansive?

    Directory of Open Access Journals (Sweden)

    Adam Szafarczyk

    2007-10-01

    Full Text Available The monetary policy plays an important role in macroeconomic policy of government. There is a question concerning type of this policy expansive or restrictive (easy or tidy monetary policy. Unfortunately, we have a lot of criteria. Each of them gives us other answer. So due to equitation of Irving Fisher we have dominantly expansive monetary policy. This same situation exists when we use nominal value of rediscount interest rate of central bank. Opposite result appears when we use real value of this interest rate or level of obligatory reserve. Taking under consideration liquidity on money market we know, that level of interest rate is too high.

  18. Optimal Policy under Restricted Government Spending

    DEFF Research Database (Denmark)

    Sørensen, Anders

    2006-01-01

    Welfare ranking of policy instruments is addressed in a two-sector Ramsey model with monopoly pricing in one sector as the only distortion. When government spending is restricted, i.e. when a government is unable or unwilling to finance the required costs for implementing the optimum policy...... effectiveness canexceed the welfare loss from introducing new distortions. Moreover, it is found that the investment subsidy is gradually phased out of the welfare maximizing policy, which may be a policy combining the two subsidies, when the level of government spending is increased.Keywords: welfare ranking...

  19. Soil seed banks in restrictive environments: dynamics and response to human disturbance.

    OpenAIRE

    Martínez Duro, Esmeralda

    2009-01-01

    Gypsum steppes and saline steppes are restrictive environments, on which factors controlling seedling recruitment and establishment in early stages are little known. Information on the factors controlling recruitment and establishment of the gypsophytes and halophytes will improve our limited knowledge on arid edaphic endemism and provide a basic tool for the management and conservation of protected ecosystems, such as gypsum outcrops and saline steppes. Abandonment of agricultural lands in l...

  20. 77 FR 24760 - Safety Advisory 2012-02; Restricted Speed

    Science.gov (United States)

    2012-04-25

    ... Federal Railroad Administration Safety Advisory 2012-02; Restricted Speed AGENCY: Federal Railroad... speed. This safety advisory contains a preliminary discussion of recent train accidents involving a failure to operate at restricted speed and makes recommendations to railroads to ensure...

  1. Medical Expenditure Panel Survey (MEPS) Restricted Data Files

    Data.gov (United States)

    U.S. Department of Health & Human Services — Restricted Data Files Available at the Data Centers Researchers and users with approved research projects can access restricted data files that have not been...

  2. Respiratory Conditions Update: Restrictive Lung Disease.

    Science.gov (United States)

    Robinson, H Coleman

    2016-09-01

    Restrictive lung diseases are a heterogeneous group of conditions characterized by a restrictive pattern on spirometry and confirmed by a reduction in total lung volume. Patients with more severe symptoms may have a reduced diffusing capacity of the lung for carbon monoxide. Etiologies can be intrinsic with lung parenchymal involvement, as in interstitial lung diseases, or extrinsic to the lung, as in obesity and neuromuscular disorders. Idiopathic pulmonary fibrosis is a chronic progressive interstitial pneumonia with fibrosis for which treatment is primarily supportive with oxygen therapy, pulmonary rehabilitation, and management of comorbid conditions. Newer drugs for idiopathic pulmonary fibrosis, such as pirfenidone and nintedanib, can slow disease progression. Referral for evaluation for lung transplantation is recommended for appropriate patients. Obstructive sleep apnea and obesity hypoventilation syndrome increasingly are common health issues, with symptoms that can include snoring, daytime somnolence, difficulty concentrating, fatigue, witnessed apneas, and morning headaches. Serum bicarbonate may serve as a biomarker in screening for subclinical obesity hypoventilation syndrome. Preoperative evaluations should assess pulmonary risk in addition to cardiac risk with a thorough history, laboratory tests, and functional capacity assessments. Optimization of management may include weight loss, pulmonary rehabilitation, oxygen therapy, and respiratory support. PMID:27576233

  3. Restrictions on Purely Kinetic K-Essence

    Institute of Scientific and Technical Information of China (English)

    YANG Rong-Jia; QI Jing-Zhao; YANG Bao-Zhu

    2011-01-01

    We restrict purely kinetic k-essence. Assuming that the equation of state is a power law of the kinetic energy, I.e. W = w0Xα, we find that a must be positive to obtain accelerated phases, constrained from the conditions for stability and causality. In this case the k-essence behaves like a phantom. We also study the evolutions of the equation of state and the speed of sound with numerical simulations.%We restrict purely kinetic k-essence.Assuming that the equation of state is a power law of the kinetic energy,i.e.ω =ω0Xα,we find that α must be positive to obtain accelerated phases,constrained from the conditions for stability and causality.In this case the k-essence behaves like a phantom.We also study the evolutions of the equation of state and the speed of sound with numerical simulations.In the last decade a convergence of independent cosmological observations have suggested that the Universe is experiencing accelerated expansion.An unknown energy component,dubbed as dark energy,has been proposed to explain this acceleration.

  4. Columbus Closure Project Released without Radiological Restrictions

    International Nuclear Information System (INIS)

    The Columbus Closure Project (CCP), a historic radiological research complex, was cleaned up for future use without radiological restriction in 2006. The CCP research and development site contributed to national defense, nuclear fuel fabrication, and the development of safe nuclear reactors in the United States until 1988 when research activities were concluded for site decommissioning. In November of 2003, the Ohio Field Office of the U.S. Department of Energy contracted ECC/E2 Closure Services, LLC (Closure Services) to complete the removal of radioactive contamination from of a 1955 era nuclear sciences area consisting of a large hot cell facility, research reactor building and underground piping. The project known as the Columbus Closure Project (CCP) was completed in 27 months and brought to a close 16 years of D and D in Columbus, Ohio. This paper examines the project innovations and challenges presented during the Columbus Closure Project. The examination of the CCP includes the project regulatory environment, the CS safety program, accelerated clean up innovation, project execution strategies and management of project waste issues and the regulatory approach to site release 'without radiological restrictions'. (authors)

  5. 9 CFR 121.13 - Restricted experiments. 10

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Restricted experiments. 10 121.13... TRANSFER OF SELECT AGENTS AND TOXINS § 121.13 Restricted experiments. 10 10 For guidance, see the NIH... entity may not conduct a restricted experiment with a VS select agent or toxin unless approved by...

  6. 36 CFR 13.1174 - Whale water restrictions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Whale water restrictions. 13... Vessel Operating Restrictions § 13.1174 Whale water restrictions. (a) May 15 through September 30, the following waters are designated as whale waters. (1) Waters north of a line drawn from Point Carolus...

  7. 48 CFR 552.203-71 - Restriction on Advertising.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Restriction on Advertising... Restriction on Advertising. As prescribed in 503.570-2, insert the following clause: Restriction on Advertising (SEP 1999) The Contractor shall not refer to this contract in commercial advertising or...

  8. 14 CFR 252.8 - Extent of smoking restrictions.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Extent of smoking restrictions. 252.8... PROCEEDINGS) ECONOMIC REGULATIONS SMOKING ABOARD AIRCRAFT § 252.8 Extent of smoking restrictions. The restrictions on smoking described in §§ 252.3 through 252.7 shall apply to all locations within the aircraft....

  9. 49 CFR 215.303 - Stenciling of restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a)...

  10. 20 CFR 332.3 - Mileage and work restrictions.

    Science.gov (United States)

    2010-04-01

    ... INSURANCE ACT MILEAGE OR WORK RESTRICTIONS AND STAND-BY OR LAY-OVER RULES § 332.3 Mileage and work... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Mileage and work restrictions. 332.3 Section... solely because of the application to him of a mileage or work restriction agreed upon in a...

  11. Oncogenic pathways impinging on the G2-restriction point

    NARCIS (Netherlands)

    Foijer, F; Simonis, M; van Vliet, M; Wessels, L; Kerkhoven, R; Sorger, P K; Te Riele, H

    2008-01-01

    In the absence of mitogenic stimuli, cells normally arrest in G(1/0), because they fail to pass the G1-restriction point. However, abrogation of the G1-restriction point (by loss of the retinoblastoma gene family) reveals a second-restriction point that arrests cells in G2. Serum-starvation-induced

  12. Gender differences in the rate of restriction to room among Ontario forensic patients.

    Science.gov (United States)

    Mathias, Krista; Hirdes, John P

    2015-07-01

    Gender can have separate and interacting effects on mental health. Gender-based analysis provides insight into these effects on mental health, and it can provide evidence to inform policy and practice to meet these gender-specific needs among persons in forensic mental health settings. Both individual and facility-level characteristics play a role in restriction to room as a form of control intervention in forensic mental health. Understanding the gender differences associated with the factors that increase a person's risk of restriction to room can allow for more targeted interventions and provide insight into policies that will help reduce these types of control interventions. PMID:26015491

  13. Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

    OpenAIRE

    Szu-Chieh Mei; Charles Brenner

    2015-01-01

    In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we develop...

  14. Prevalence of Spirometrically-defined Restrictive Ventilatory Defect in Korea: The Fourth-2, 3, and Fifth Korean National Health and Nutrition Examination Survey, 2008-2012

    OpenAIRE

    Lee, Jung Yeon; Hwang, Yong Il; Park, Yong Bum; Park, Jae Yong; Kim, Ki Uk; Oh, Yeon-Mok; Yoon, Hyoung Kyu; Yoon, Ho Il; Sheen, Sueng Su; Lee, Sang Yeub; Lee, Chang-Hoon; Lee, Heung Bum; Lim, Sung Chul; Jung, Sung Soo; Oh, Kyungwon

    2015-01-01

    The aim of the study was to evaluate the prevalence of restrictive ventilatory defect and to determine the risk factors in subjects with spirometrically-defined restrictive ventilatory defect. We used the population-based, fourth-2, 3 (2008, 2009) and fifth (2010-2012) Korea National Health and Nutrition Examination Survey (KNHANES) to analyze 15,073 subjects, aged ≥40 yr who underwent spirometry. Chest radiographs were also analyzed to identify restrictive lung disease. Spirometrically-defin...

  15. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    Science.gov (United States)

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties. PMID:25669112

  16. Restricted Edge Connectivity of BinaryUndirected Kautz Graphs

    Institute of Scientific and Technical Information of China (English)

    OUJian-ping

    2004-01-01

    A restricted edge cut is an edge cut of a connected graph whose removal resultsin a disconnected graph without isolated vertices. The size of a minimum restricted edge cutof a graph G is called its restricted edge connectivity, and is denoted by λ′(G). Let ξ(G) bethe minimum edge degree of graph G. It is known that λ′(G) ≤ξ(G) if G contains restrictededge cuts. Graph G is called maximal restricted edge connected if the equality holds in thethe preceding inequality. In this paper, undirected Kautz graph UK(2, n) is proved to bemaximal restricted edge connected if n ≥ 2.

  17. A FORTRAN Program for Correcting Correlation Coefficients for Restriction in Range for Explicit or Implicit Restriction.

    Science.gov (United States)

    Lewis, Mary A.; Boone, James O.

    1979-01-01

    Restriction in range is a measurement problem frequently encountered in research studies that utilize correlation coefficients. A FORTRAN program is described that can compute the estimated unrestricted correlation coefficient in either the explicit or implicit case. The user selects the appropriate formula to be employed from five that are…

  18. Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag

    Directory of Open Access Journals (Sweden)

    Woods Matthew W

    2011-11-01

    Full Text Available Abstract Background The identification and characterization of several interferon (IFN-induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta-induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5 that blocks a unique late stage of the HIV-1 life cycle. Results HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus. Conclusions HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy.

  19. THE TSC COMPLEX IS REQUIRED FOR THE BENEFITS OF DIETARY PROTEIN RESTRICTION ON STRESS RESISTANCE IN VIVO

    OpenAIRE

    Eylul Harputlugil; Christopher Hine; Dorathy Vargas; Lauren Robertson; Brendan D. Manning; James R. Mitchell

    2014-01-01

    Protein restriction (PR) is important for the benefits of dietary restriction on longevity and stress resistance, but relevant nutrient sensors and downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements for the evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance. One week of PR reduced free amino acids and circulating growth factors, activating GCN2 and mTORC1 repre...

  20. Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Richard C Grandison

    Full Text Available BACKGROUND: Outcomes of lifespan studies in model organisms are particularly susceptible to variations in technical procedures. This is especially true of dietary restriction, which is implemented in many different ways among laboratories. PRINCIPAL FINDINGS: In this study, we have examined the effect of laboratory stock maintenance, genotype differences and microbial infection on the ability of dietary restriction (DR to extend life in the fruit fly Drosophila melanogaster. None of these factors block the DR effect. CONCLUSIONS: These data lend support to the idea that nutrient restriction genuinely extends lifespan in flies, and that any mechanistic discoveries made with this model are of potential relevance to the determinants of lifespan in other organisms.

  1. Formation reconfiguration in restricted three body problem

    Institute of Scientific and Technical Information of China (English)

    Shengping Gong; Junfeng Li; Hexi Baoyin; Yunfeng Gao

    2007-01-01

    Reconfiguration of formation flying around a halo orbit of the Sun-Earth restricted three body system is investigated with impulse maneuvers. For a short time reconfiguration, the two-impulse maneuver is investigated with both analytical and numerical methods and the BeginningEnding (BE) method is proven to be an energy-optimal one of all two-impulse (TI) reconfigurations, and the energy consumption of BE is independent of the position of the chief spacecraft, and decreases with the reconfiguration time.Then, genetic algorithm is adopted to optimize the energy consumption. The results show that the optimal energy increases with radius difference between the initial and final orbits, and decreases with the reconfiguration time.

  2. Membrane barriers for radon gas flow restrictions

    International Nuclear Information System (INIS)

    Research was performed to assess the feasibility of barrier membrane substances, for use within mining or associated high risk environments, in restricting the diffusion transport of radon gas quantities. Specific tests were conducted to determine permeability parameters of a variety of membrane materials with reference to radon flow capabilities. Tests were conducted both within laboratory and in-situ emanation environments where concentrations and diffusion flows of radon gas were known to exist. Equilibrium radon gas concentrations were monitored in initially radon-free chambers adjacent to gas sources, but separated by specified membrane substances. Membrane barrier effectiveness was demonstrated to result in reduced emanation concentrations of radon gas within the sampling chamber atmosphere. Minimum gas concentrations were evidenced where the barrier membrane material was shown to exhibit lowest radon permeability characteristics

  3. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  4. Constrictive Pericarditis Versus Restrictive Cardiomyopathy?

    Science.gov (United States)

    Garcia, Mario J

    2016-05-01

    About one-half of the patients with congestive heart failure have preserved left ventricular ejection fraction (HFpEF). Although the etiology of HFpEF is most commonly related to long-standing hypertension and atherosclerosis, a significant number of suspected HFpEF patients have a restrictive cardiomyopathy or chronic pericardial disease. Recognizing these syndromes is important because early diagnosis may lead to instituting specific therapy that may prolong survival, improve quality of life, and/or recognize and treat an underlying systemic disorder. Advances in diagnostic imaging, biomarkers, and genetic testing today allow identification of the specific etiology in most cases. Novel pharmacological, immunologic, and surgical therapies are leading to improved quality of life and survival.

  5. Restriction modification systems as engines of diversity.

    Science.gov (United States)

    Sneppen, Kim; Semsey, Szabolcs; Seshasayee, Aswin S N; Krishna, Sandeep

    2015-01-01

    Restriction modification (RM) systems provide protection against a broad spectrum of phages. However, the likelihood of a phage permanently bypassing this can be as high as 0.1 per infection (Korona et al., 1993) which makes for a relatively weak defense. Here we argue that, apart from providing such transient defenses, RM systems can facilitate long-term coexistence of many bacterial strains. We show that this diversity can be as large as the burst size of the phage but no larger-a curious correspondence between a number at the level of species and another number at the level of individuals. Such a highly diverse and stably coexisting ecosystem is robust to substantial variation in both bacterial growth rates and strength of their RM systems, which might be one reason why quite weak RM systems exist in the wild. PMID:26082758

  6. Restriction Modification Systems as Engines of Diversity

    Directory of Open Access Journals (Sweden)

    Kim eSneppen

    2015-06-01

    Full Text Available Restriction modification (RM systems provide protection against a broad spectrum of phages. However, the likelihood of a phage permanently bypassing this can be as high as 0.1 per infection (Korona et al., J. Gen. Microbiol. 139: 1283-1290, 1993 which makes for a relatively weak defence. Here we argue that, apart from providing such transient defences, RM systems can facilitate long-term coexistence of many bacterial strains. We show that this diversity can be as large as the burst size of the phage but no larger -- a curious correspondence between a number at the level of species and another number at the level of individuals. Such a highly diverse and stably coexisting ecosystem is robust to substantial variation in both bacterial growth rates and strength of their RM systems, which might be one reason why quite weak RM systems exist in the wild.

  7. Epitaxial growth by monolayer restricted galvanic displacement

    Directory of Open Access Journals (Sweden)

    Vasilić Rastko

    2012-01-01

    Full Text Available The development of a new method for epitaxial growth of metals in solution by galvanic displacement of layers pre-deposited by underpotential deposition (UPD was discussed and experimentally illustrated throughout the lecture. Cyclic voltammetry (CV and scanning tunneling microscopy (STM are employed to carry out and monitor a “quasi-perfect”, two-dimensional growth of Ag on Au(111, Cu on Ag(111, and Cu on Au(111 by repetitive galvanic displacement of underpotentially deposited monolayers. A comparative study emphasizes the displacement stoichiometry as an efficient tool for thickness control during the deposition process and as a key parameter that affects the deposit morphology. The excellent quality of layers deposited by monolayer-restricted galvanic displacement is manifested by a steady UPD voltammetry and ascertained by a flat and uniform surface morphology maintained during the entire growth process.

  8. Autotagging music with conditional restricted Boltzmann machines

    CERN Document Server

    Mandel, Michael; Larochelle, Hugo; Bengio, Yoshua

    2011-01-01

    This paper describes two applications of conditional restricted Boltzmann machines (CRBMs) to the task of autotagging music. The first consists of training a CRBM to predict tags that a user would apply to a clip of a song based on tags already applied by other users. By learning the relationships between tags, this model is able to pre-process training data to significantly improve the performance of a support vector machine (SVM) autotagging. The second is the use of a discriminative RBM, a type of CRBM, to autotag music. By simultaneously exploiting the relationships among tags and between tags and audio-based features, this model is able to significantly outperform SVMs, logistic regression, and multi-layer perceptrons. In order to be applied to this problem, the discriminative RBM was generalized to the multi-label setting and four different learning algorithms for it were evaluated, the first such in-depth analysis of which we are aware.

  9. AGORA: Assembly Guided by Optical Restriction Alignment

    Directory of Open Access Journals (Sweden)

    Lin Henry C

    2012-08-01

    Full Text Available Abstract Background Genome assembly is difficult due to repeated sequences within the genome, which create ambiguities and cause the final assembly to be broken up into many separate sequences (contigs. Long range linking information, such as mate-pairs or mapping data, is necessary to help assembly software resolve repeats, thereby leading to a more complete reconstruction of genomes. Prior work has used optical maps for validating assemblies and scaffolding contigs, after an initial assembly has been produced. However, optical maps have not previously been used within the genome assembly process. Here, we use optical map information within the popular de Bruijn graph assembly paradigm to eliminate paths in the de Bruijn graph which are not consistent with the optical map and help determine the correct reconstruction of the genome. Results We developed a new algorithm called AGORA: Assembly Guided by Optical Restriction Alignment. AGORA is the first algorithm to use optical map information directly within the de Bruijn graph framework to help produce an accurate assembly of a genome that is consistent with the optical map information provided. Our simulations on bacterial genomes show that AGORA is effective at producing assemblies closely matching the reference sequences. Additionally, we show that noise in the optical map can have a strong impact on the final assembly quality for some complex genomes, and we also measure how various characteristics of the starting de Bruijn graph may impact the quality of the final assembly. Lastly, we show that a proper choice of restriction enzyme for the optical map may substantially improve the quality of the final assembly. Conclusions Our work shows that optical maps can be used effectively to assemble genomes within the de Bruijn graph assembly framework. Our experiments also provide insights into the characteristics of the mapping data that most affect the performance of our algorithm, indicating the

  10. Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells

    International Nuclear Information System (INIS)

    The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors

  11. Peptide Inhibitors of HIV-1 Virus Infection Based on Cullin-5

    Institute of Scientific and Technical Information of China (English)

    ZHU Ke-tong; ZHANG Xi-zhen; LOU Chao-ping; GUO Bo; DU Juan; WANG Xiao-dan; WU Yong-ge; KONG Wei; YU Xiang-hui

    2008-01-01

    Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed in "nonpermissive" cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors' took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family,respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in "nonpermissive" cells with a dose-responsive manner, but not in "permissive" cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.

  12. Restriction of bacteriophage plaque formation in Streptomyces spp.

    Science.gov (United States)

    Cox, K L; Baltz, R H

    1984-08-01

    Several Streptomyces species that produce restriction endonucleases were characterized for their ability to propagate 10 different broad host range bacteriophages. Each species displayed a different pattern of plaque formation. A restrictionless mutant of S. albus G allowed plaque formation by all 10 phages, whereas the wild-type strain showed plaques with only 2 phages. DNA isolated from three of the phages was analyzed for the presence of restriction sites for Streptomyces species-encoded enzymes, and a very strong correlation was established between the failure to form plaques on Streptomyces species that produced particular restriction enzymes and the presence of the corresponding restriction sites in the phage DNA. Also, the phages that lacked restriction sites in their DNA generally formed plaques on the corresponding restriction endonuclease-producing hosts at high efficiency. The DNAs from the three phages analyzed also generally contained either many or no restriction sites for the Streptomyces species-produced enzymes, suggesting a strong evolutionary trend to either eliminate all or tolerate many restriction sites. The data indicate that restriction plays a major role in host range determination for Streptomyces phages. Analysis of bacteriophage host ranges of many other uncharacterized Streptomyces hosts has identified four relatively nonrestricting hosts, at least two of which may be suitable hosts for gene cloning. The data also suggest that several restriction systems remain to be identified in the genus Streptomyces.

  13. Restrictive influence of SAMHD1 on Hepatitis B Virus life cycle

    Science.gov (United States)

    Sommer, Andreas F. R.; Rivière, Lise; Qu, Bingqian; Schott, Kerstin; Riess, Maximilian; Ni, Yi; Shepard, Caitlin; Schnellbächer, Esther; Finkernagel, Malin; Himmelsbach, Kiyoshi; Welzel, Karin; Kettern, Nadja; Donnerhak, Christian; Münk, Carsten; Flory, Egbert; Liese, Juliane; Kim, Baek; Urban, Stephan; König, Renate

    2016-01-01

    Deoxynucleotide triphosphates (dNTPs) are essential for efficient hepatitis B virus (HBV) replication. Here, we investigated the influence of the restriction factor SAMHD1, a dNTP hydrolase (dNTPase) and RNase, on HBV replication. We demonstrated that silencing of SAMHD1 in hepatic cells increased HBV replication, while overexpression had the opposite effect. SAMHD1 significantly affected the levels of extracellular viral DNA as well as intracellular reverse transcription products, without affecting HBV RNAs or cccDNA. SAMHD1 mutations that interfere with the dNTPase activity (D137N) or in the catalytic center of the histidine-aspartate (HD) domain (D311A), and a phospho-mimetic mutation (T592E), abrogated the inhibitory activity. In contrast, a mutation diminishing the potential RNase but not dNTPase activity (Q548A) and a mutation disabling phosphorylation (T592A) did not affect antiviral activity. Moreover, HBV restriction by SAMHD1 was rescued by addition of deoxynucleosides. Although HBV infection did not directly affect protein level or phosphorylation of SAMHD1, the virus upregulated intracellular dATPs. Interestingly, SAMHD1 was dephosphorylated, thus in a potentially antiviral-active state, in primary human hepatocytes. Furthermore, SAMHD1 was upregulated by type I and II interferons in hepatic cells. These results suggest that SAMHD1 is a relevant restriction factor for HBV and restricts reverse transcription through its dNTPase activity. PMID:27229711

  14. Reshuffling and Relocating: The Gendered and Income-Related Differential Effects of Restricting Smoking Locations

    Directory of Open Access Journals (Sweden)

    Natalie Hemsing

    2012-01-01

    Full Text Available This study investigates secondhand smoke (SHS exposure and management in the context of smoking location restrictions, for nonsmokers, former, and current smokers. A purposive sample of 47 low income and non-low-income men and women of varied smoking statuses was recruited to participate in a telephone interview or a focus group. Amidst general approval of increased restrictions there were gendered patterns of SHS exposure and management, and effects of SHS policies that reflect power, control, and social roles that need to be considered as policies are developed, implemented and monitored. The experience of smoking restrictions and the management of SHS is influenced by the social context (relationship with a partner, family member, or stranger, the space of exposure (public or private, worksite, the social location of individuals involved (gender, income, and differential tolerance to SHS. This confluence of factors creates differing unintended and unexpected consequences to the social and physical situations of male and female smokers, nonsmokers, and former smokers. These factors deserve further study, in the interests of informing the development of future interventions and policies restricting SHS.

  15. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway.

    Science.gov (United States)

    Hine, Christopher; Mitchell, James R

    2015-08-01

    H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action.

  16. Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway.

    Science.gov (United States)

    Hine, Christopher; Mitchell, James R

    2015-08-01

    H2S is a gas easily identified by its distinctive odor. Although environmental exposure to H2S has been viewed alternately as therapeutic or toxic through the centuries, H2S has recently regained recognition for its numerous beneficial biological effects. Most experiments documenting such benefits, including improved glucose tolerance, increased stress resistance, and even lifespan extension, are based on exposure of experimental organisms to exogenous sources of H2S. However, appreciation is growing for the importance of H2S produced endogenously by the evolutionary conserved transsulfuration pathway (TSP) in health and longevity. Recent data implicate H2S produced by the TSP in pleiotropic benefits of dietary restriction (DR), or reduced nutrient/energy intake without malnutrition. DR, best known as the most reliable way to extend lifespan in a wide range of experimental organisms, includes various regimens aimed at either reducing overall calorie intake (calorie restriction, intermittent/every-other-day fasting) or reducing particular nutrients such as protein or the essential amino acid, methionine (methionine restriction), with overlapping functional benefits on stress resistance, metabolic fitness and lifespan. Here we will review the small but growing body of literature linking the TSP to the functional benefits of DR in part through the production of endogenous H2S, with an emphasis on regulation of the TSP and H2S production by diet and mechanisms of beneficial H2S action. PMID:25523462

  17. A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator

    Directory of Open Access Journals (Sweden)

    Hanhui Ye

    2016-01-01

    Full Text Available Human immunodeficiency virus causes a severe disease in humans, referred to as immune deficiency syndrome. Studies on the interaction between host genetic factors and the virus have revealed dozens of genes that impact diverse processes in the AIDS disease. To resolve more genetic factors related to AIDS, a canonical correlation analysis was used to determine the correlation between AIDS restriction and metabolic pathway gene expression. The results show that HIV-1 postentry cellular viral cofactors from AIDS restriction genes are coexpressed in human transcriptome microarray datasets. Further, the purine metabolism pathway comprises novel host factors that are coexpressed with AIDS restriction genes. Using a canonical correlation analysis for expression is a reliable approach to exploring the mechanism underlying AIDS.

  18. Near BPS Skyrmions and Restricted Harmonic Maps

    CERN Document Server

    Speight, J M

    2014-01-01

    Motivated by a class of near BPS Skyrme models introduced by Adam, S\\'anchez-Guill\\'en and Wereszczy\\'nski, the following variant of the harmonic map problem is introduced: a map $\\phi:(M,g)\\rightarrow (N,h)$ between Riemannian manifolds is restricted harmonic (RH) if it locally extremizes $E_2$ on its $SDiff(M)$ orbit, where $SDiff(M)$ denotes the group of volume preserving diffeomorphisms of $(M,g)$, and $E_2$ denotes the Dirichlet energy. It is conjectured that near BPS skyrmions tend to RH maps in the BPS limit. It is shown that $\\phi$ is RH if and only if $\\phi^*h$ has exact divergence, and a linear stability theory of RH maps is developed, whence it follows that all weakly conformal maps, for example, are stable RH. Examples of RH maps in every degree class $R^3\\to SU(2)$ and $R^2\\to S^2$ are constructed. It is shown that the axially symmetric BPS skyrmions on which all previous analytic studies of near BPS Skyrme models have been based, are not RH, so each such field can be deformed along $SDiff(R^3)$ ...

  19. Second law of thermodynamics under control restrictions.

    Science.gov (United States)

    Wilming, H; Gallego, R; Eisert, J

    2016-04-01

    The second law of thermodynamics, formulated as an ultimate bound on the maximum extractable work, has been rigorously derived in multiple scenarios. However, the unavoidable limitations that emerge due to the lack of control on small systems are often disregarded when deriving such bounds, which is specifically important in the context of quantum thermodynamics. Here we study the maximum extractable work with limited control over the working system and its interaction with the heat bath. We derive a general second law when the set of accessible Hamiltonians of the working system is arbitrarily restricted. We then apply our bound to particular scenarios that are important in realistic implementations: limitations on the maximum energy gap and local control over many-body systems. We hence demonstrate in what precise way the lack of control affects the second law. In particular, contrary to the unrestricted case, we show that the optimal work extraction is not achieved by simple thermal contacts. Our results not only generalize the second law to scenarios of practical relevance, but also take first steps in the direction of local thermodynamics. PMID:27176273

  20. Maternal dietary restriction alters offspring's sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Noriyuki Shimizu

    Full Text Available Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD or 50% dietary restriction (DR groups from gestation day 12 to parturition. After parturition, dams were fed AD chow. After weaning, the pups were also fed AD into adulthood. At adulthood (aged 8-9 weeks, we carried out sleep recordings. Although offspring mice displayed a significantly reduced body weight at birth, their weights recovered three days after birth. Enhancement of electroencephalogram (EEG slow wave activity (SWA during non-rapid eye movement (NREM sleep was observed in the DR mice over a 24-hour period without changing the diurnal pattern or amounts of wake, NREM, or rapid eye movement (REM sleep. In addition, DR mice also displayed an enhancement of EEG-SWA rebound after a 6-hour sleep deprivation and a higher threshold for waking in the face of external stimuli. DR adult offspring mice exhibited small but significant increases in the expression of hypothalamic peroxisome proliferator-activated receptor α (Pparα and brain-specific carnitine palmitoyltransferase 1 (Cpt1c mRNA, two genes involved in lipid metabolism. Undernutrition during pregnancy may influence sleep homeostasis, with offspring exhibiting greater sleep pressure.

  1. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects

    Science.gov (United States)

    Sharma, Deepak; Shastri, Sweta; Sharma, Pradeep

    2016-01-01

    Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR. PMID:27441006

  2. What you should know about restrictive covenants in health care.

    Science.gov (United States)

    Austin, Michael G; Grosack, Matthew

    2013-01-01

    In recent years, many states have shown a greater inclination to enforce restrictive covenant provisions in contracts involving healthcare organizations and their employees, physicians, or other contacting parties. In general, an enforceable restrictive covenant is one that is deemed to have been reasonably drafted to do no more than to protect the company's legitimate business interest. Key areas of concern in health care that often fall under the protection of restrictive covenants include patient referral sources and relationships with patients. PMID:23360060

  3. How restriction enzymes became the workhorses of molecular biology

    OpenAIRE

    Roberts, Richard J.

    2005-01-01

    Restriction enzymes have proved to be invaluable for the physical mapping of DNA. They offer unparalleled opportunities for diagnosing DNA sequence content and are used in fields as disparate as criminal forensics and basic research. In fact, without restriction enzymes, the biotechnology industry would certainly not have flourished as it has. The first experiments demonstrating the utility of restriction enzymes were carried out by Danna and Nathans and reported in 1971. This pioneering stud...

  4. Earth system multi-body restriction dynamics model research

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qingxian; BI Siwen; GONG Huili

    2006-01-01

    Research provides a theoretical basis for an Earth system multi-body mechanics model and its dynamics, including the Earth system multi-body restriction function and its power, Earth system multi-body restriction under decreasing generalized velocity and decreasing partial palstance, the Earth system multi-body decreasing generalized force, a moving mechanics function, and the Earth system multi-body restriction's wattful and wattless forces.

  5. Health promotion by dietary restriction--a focus.

    Science.gov (United States)

    Ramkumar, K M

    2006-01-01

    Food restriction, although long popular among gerontologists, has emerged as a new challenge in public health in postindustrial societies because this is the only intervention that repeatedly and strikingly increases maximum life span. The practice of food restriction is widespread for cosmetic, health, and economic reasons. The beneficial effects and the molecular mechanism of food restriction have been well established. The present review summarizes the rapidly accumulating evidence on the involvement of food restriction in various diseases and focuses on good dietary practices for health promotion in modern life style. PMID:16910315

  6. Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1

    International Nuclear Information System (INIS)

    In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5α with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain

  7. Photo-Crosslinking Induced Geometric Restriction Controls the Self-Assembly of Diphenylalanine Based Peptides

    Institute of Scientific and Technical Information of China (English)

    TIE Zuo-Xiu; QIN Meng; ZOU Da-Wei; CAO Yi; WANG Wei

    2011-01-01

    @@ The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels.In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by n - TT stacking among the phenyl groups.Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions.Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous.%The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π - π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive “smart”materials.

  8. Dietary restriction: could it be considered as speed bump on tumor progression road?

    Science.gov (United States)

    Cangemi, Antonina; Fanale, Daniele; Rinaldi, Gaetana; Bazan, Viviana; Galvano, Antonio; Perez, Alessandro; Barraco, Nadia; Massihnia, Daniela; Castiglia, Marta; Vieni, Salvatore; Bronte, Giuseppe; Mirisola, Mario; Russo, Antonio

    2016-06-01

    Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes. PMID:27043958

  9. Dietary restriction: could it be considered as speed bump on tumor progression road?

    Science.gov (United States)

    Cangemi, Antonina; Fanale, Daniele; Rinaldi, Gaetana; Bazan, Viviana; Galvano, Antonio; Perez, Alessandro; Barraco, Nadia; Massihnia, Daniela; Castiglia, Marta; Vieni, Salvatore; Bronte, Giuseppe; Mirisola, Mario; Russo, Antonio

    2016-06-01

    Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.

  10. Determinants of participation restriction among community dwelling stroke survivors: A path analysis

    Directory of Open Access Journals (Sweden)

    Chang Anne M

    2009-09-01

    Full Text Available Abstract Background Apart from promoting physical recovery and assisting in activities of daily living, a major challenge in stroke rehabilitation is to minimize psychosocial morbidity and to promote the reintegration of stroke survivors into their family and community. The identification of key factors influencing long-term outcome are essential in developing more effective rehabilitation measures for reducing stroke-related morbidity. The aim of this study was to test a theoretical model of predictors of participation restriction which included the direct and indirect effects between psychosocial outcomes, physical outcome, and socio-demographic variables at 12 months after stroke. Methods Data were collected from 188 stroke survivors at 12 months following their discharge from one of the two rehabilitation hospitals in Hong Kong. The settings included patients' homes and residential care facilities. Path analysis was used to test a hypothesized model of participation restriction at 12 months. Results The path coefficients show functional ability having the largest direct effect on participation restriction (β = 0.51. The results also show that more depressive symptoms (β = -0.27, low state self-esteem (β = 0.20, female gender (β = 0.13, older age (β = -0.11 and living in a residential care facility (β = -0.12 have a direct effect on participation restriction. The explanatory variables accounted for 71% of the variance in explaining participation restriction at 12 months. Conclusion Identification of stroke survivors at risk of high levels of participation restriction, depressive symptoms and low self-esteem will assist health professionals to devise appropriate rehabilitation interventions that target improving both physical and psychosocial functioning.

  11. Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats.

    Science.gov (United States)

    de Rijke, C E; Hillebrand, J J G; Verhagen, L A W; Roeling, T A P; Adan, R A H

    2005-10-01

    When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.

  12. Comparison of a Restricted and Unrestricted Vegan Diet Plan with a Restricted Omnivorous Diet Plan on Health-Specific Measures

    OpenAIRE

    Bloomer, Richard J; Gunnels, Trint A; JohnHenry M. Schriefer

    2015-01-01

    Background: We have previously noted beneficial health outcomes when individuals follow a dietary restriction plan in accordance with the Daniel Fast (DF). This is true whether individuals eliminate all animal products or include small amounts of meat and dairy in their plan. The present study sought to compare anthropometric and biochemical measures of health in individuals following a traditional DF (i.e., restricted vegan) or modified DF (i.e., restricted omnivorous; inclusive of ad libitu...

  13. Impact of Six-Month Caloric Restriction on Autonomic Nervous System Activity in Healthy, Overweight, Individuals

    OpenAIRE

    de Jonge, Lillian; Moreira, Emilia AM; Martin, Corby K.; Ravussin, Eric

    2009-01-01

    Caloric restriction (CR) increases maximum lifespan but the mechanisms are unclear. Dominance of the sympathetic nervous System (SNS) over the Parasympathetic Nervous System (PNS) has been shown to be a strong risk factor for cardiovascular disease. Obesity and aging are associated with increased SNS activity and weight loss and/or exercise seem to have positive effects on this balance. We therefore evaluated the effect of different approaches of CR on autonomic function in 48 overweight indi...

  14. Alterations induced by juvenile obesity on the renal tissue of nutrient restricted offspring

    OpenAIRE

    Fainberg, Hernan Pablo

    2010-01-01

    Human epidemiological studies have indentified obesity as an independent risk factor for renal disease. In addition, maternal nutrient restriction (MNR) during gestation results in a series of adaptations that may predispose those offspring to obesity and hypertension. Recent reports demonstrated that obese sheep exposed to MNR during early to mid gestation have a predisposition to ectopic lipid deposition in the heart and a rise in necrotic adipocytes, which are markers of severe metabolic d...

  15. The role and regulation of IGFBP-1 phosphorylation in fetal growth restriction

    OpenAIRE

    Gupta, Madhulika B.

    2015-01-01

    Fetal growth restriction (FGR) increases the risk of perinatal complications and predisposes the infant to developing metabolic, cardiovascular, and neurological diseases in childhood and adulthood. The pathophysiology underlying FGR remains poorly understood and there is no specific treatment available. Biomarkers for early detection are also lacking. The insulin-like growth factor (IGF) system is an important regulator of fetal growth. IGF-I is the primary regulator of fetal growth, and fet...

  16. The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells.

    Science.gov (United States)

    Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M; Vives-Pi, Marta; Esté, José A; Ballana, Ester

    2016-08-01

    Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

  17. Alteration of the Specificity of PstⅠRestriction Endonuclease

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The influence of factors on the substrate-specificity of Pst Ⅰ restriction endonuclease has been studied with the method of electrophoresis. The results show that, the specificity of Pst Ⅰ almost can not be influenced by the single alteration of the concentration of Tris*HCl, Mg2+ or Na+ in the reaction system, but it can be altered by the reduction of any two of them. The specificity can not be altered by the single alteration of pH or the replacement of Mg2+ with Mn2+. The addition of glycerol or dimethylsulphoxide (DMSO) to the reaction system results in the relaxation of the substrate-specificity of Pst Ⅰ , but dimethylmethylformide, glycol and ethyl alcohol can not bring about the alteration of Pst Ⅰ specificity. Through the method of cloning and sequencing, the nucleotides of No.1 and 6 in the recognition sequence of Pst Ⅰ have changed (1C→A or 6G→T). Used with the enzyme analysis of an artificially synthetic DNA segment containing a special sequence, the nucleotides of No.1 and 6 have both changed (1C→A and 6G→T). The recognition sequence of Pst Ⅰ is speculated to be changed from CTGCA↓G to TGCA↓.

  18. Tetherin restricts productive HIV-1 cell-to-cell transmission.

    Directory of Open Access Journals (Sweden)

    Nicoletta Casartelli

    Full Text Available The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24 impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or DeltaVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DeltaVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.

  19. 7 CFR 331.13 - Restricted experiments. 5

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Restricted experiments. 5 331.13 Section 331.13... Restricted experiments. 5 5 For guidance, see the NIH publication, “NIH Guidelines for Research Involving.../ag_selectagent/index.html. (a) An individual or entity may not conduct the following...

  20. The challenge of cost restrictions in smile design.

    Science.gov (United States)

    Feigenbaum, N

    1991-09-01

    This article demonstrates a method for smile enhancement involving the familiar "gummy" smile as well as irregular incisor gingival emergence levels. In this case study, financial considerations limited a comprehensive restorative treatment plan, restricting changes to several anterior teeth. Despite the restrictions, a solution was found.

  1. 29 CFR 530.2 - Restriction of homework.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Restriction of homework. 530.2 Section 530.2 Labor... OF HOMEWORKERS IN CERTAIN INDUSTRIES General § 530.2 Restriction of homework. Except as provided in... special homework certificate issued and in effect pursuant to this part has been obtained for...

  2. 48 CFR 1403.570 - Restrictions on contractor advertising.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Restrictions on contractor advertising. 1403.570 Section 1403.570 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... 1403.570 Restrictions on contractor advertising....

  3. 32 CFR 516.5 - Restriction on contact with DOJ.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Restriction on contact with DOJ. 516.5 Section 516.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION General § 516.5 Restriction on contact with DOJ. (a) General...

  4. 34 CFR 76.566 - Fixed costs-restricted rate.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Fixed costs-restricted rate. 76.566 Section 76.566 Education Office of the Secretary, Department of Education STATE-ADMINISTERED PROGRAMS What Conditions Must Be Met by the State and Its Subgrantees? Indirect Cost Rates § 76.566 Fixed costs—restricted rate....

  5. Reduced Automatic Motivational Orientation Towards Food in Restricting Anorexia Nervosa

    NARCIS (Netherlands)

    Veenstra, Esther M.; de Jong, Peter J.

    2011-01-01

    A striking and characteristic feature of the restricting subtype of anorexia nervosa (AN) is that they are extremely successful in regulating their food intake in a destructive manner. A possible explanation for the persistent character of their restricted food intake could be a loss of the motivati

  6. Reverse triple I method of restriction for fuzzy reasoning

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A theory of reverse triple I method of restriction for implication operator R0 is proposed.And the general computation formulas of infimum for fuzzy modus ponens and supremum for fuzzy modus tollens of a-reverse triple I method of restriction are obtained respectively.

  7. 7 CFR 319.75-2 - Restricted articles. 1

    Science.gov (United States)

    2010-01-01

    ... other provisions of 7 CFR part 319. For example, fresh whole chilies (Capsicum spp.) and fresh whole red... be subject to additional restrictions under the provisions in 7 CFR 319.8 et seq. (6) Used jute or... 7 Agriculture 5 2010-01-01 2010-01-01 false Restricted articles. 1 319.75-2 Section...

  8. 40 CFR 152.175 - Pesticides classified for restricted use.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pesticides classified for restricted...) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Classification of Pesticides § 152.175 Pesticides classified for restricted use. The following uses of pesticide products containing...

  9. Consequences of intrauterine growth restriction for the kidney

    NARCIS (Netherlands)

    M.F. Schreuder; A. van Wijk (Ans); H.A. Delemarre-van de Waal (Henriette)

    2006-01-01

    textabstractLow birth weight due to intrauterine growth restriction is associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance and end-stage renal disease. The purpose of this review is to describe the effects of intrauterine growth restriction

  10. Effect of feed restriction on performance of growing rabbits

    Directory of Open Access Journals (Sweden)

    Maria Cristina de Oliveira

    2012-06-01

    Full Text Available This experiment assessed the effect of feed restriction in rabbits on performance and economic viability of the activity. Sixty New Zealand White rabbits, weaned at 33 days and slaughtered at 81 days of age, were used. The design was of randomized blocks with four treatments and five replications. The treatments were, as follows: 1 - free feeding, 2 - feed restriction from 35 to 40 days of age (50 g/d/rabbit, 3 - feed restriction from 54 to 61 days of age (90 g/d/rabbit and 4 - feed restriction from 33 to 40 days (50 g/d/rabbit and from 54 to 61 days of age (90 g/d/rabbit. There was no difference in the performance and carcass parameters, indicating that there was compensatory growth in the rabbits that suffered feed restriction. The best gross margin was obtained with feed restriction from 54 to 61 days age. Feed restriction in growing rabbits can be adopted at different ages because it does not interfere negatively in the performance and carcass parameters. In two periods and from 51 to 61 days, feed restriction was more economically viable for the sale of live and slaughtered rabbits, respectively.

  11. 7 CFR 800.76 - Prohibited services; restricted services.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Prohibited services; restricted services. 800.76..., PACKERS AND STOCKYARD ADMINISTRATION (FEDERAL GRAIN INSPECTION SERVICE), DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS Kinds of Official Services § 800.76 Prohibited services; restricted services. (a)...

  12. On some Frobenius Restriction Theorems for Semistable Sheaves

    Indian Academy of Sciences (India)

    V B Mehta; V Trivedi

    2009-02-01

    We prove a version of an effective Frobenius restriction theorem for semistable bundles in characteristic . The main novelty is in restricting the bundle to the -fold thickening of a hypersurface section. The base variety is /, an abelian variety or a smooth projective toric variety.

  13. 30 CFR 57.4461 - Gasoline use restrictions underground.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Gasoline use restrictions underground. 57.4461... Prevention and Control Flammable and Combustible Liquids and Gases § 57.4461 Gasoline use restrictions underground. If gasoline is used underground to power internal combustion engines— (a) The mine shall...

  14. 32 CFR 538.3 - Restrictions on possession and use.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Restrictions on possession and use. 538.3 Section... MILITARY PAYMENT CERTIFICATES § 538.3 Restrictions on possession and use. (a) Possession or use prohibited. Possession or use of military payment certificates is prohibited unless acquired in accordance with §§...

  15. 50 CFR 648.235 - Possession and landing restrictions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Possession and landing restrictions. 648... Measures for the Spiny Dogfish Fishery § 648.235 Possession and landing restrictions. (a) Quota Period 1... calendar day. (c) Regulations governing the harvest, possession, landing, purchase, and sale of shark...

  16. 32 CFR 1903.16 - Restriction on animals.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Restriction on animals. 1903.16 Section 1903.16... AGENCY INSTALLATIONS § 1903.16 Restriction on animals. Animals, except for those animals used for the assistance of persons with disabilities, or animals under the charge and control of the Central...

  17. 32 CFR 234.12 - Restriction on animals.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Restriction on animals. 234.12 Section 234.12 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS CONDUCT ON THE PENTAGON RESERVATION § 234.12 Restriction on animals. Animals, except guide...

  18. 32 CFR 228.15 - Restriction regarding animals.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Restriction regarding animals. 228.15 Section 228.15 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS SECURITY PROTECTIVE FORCE § 228.15 Restriction regarding animals. No animals...

  19. Acute sleep restriction reduces insulin sensitivity in adolescent boys

    DEFF Research Database (Denmark)

    Klingenberg, Lars; Chaput, Jean-Philippe; Holmbäck, Ulf;

    2013-01-01

    Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction.......Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction....

  20. 24 CFR 2004.26 - Restrictions that apply to testimony.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Restrictions that apply to testimony. 2004.26 Section 2004.26 Housing and Urban Development Regulations Relating to Housing and Urban... Production of Documents § 2004.26 Restrictions that apply to testimony. (a) The Counsel may impose...

  1. 75 FR 61612 - Airports/Locations: Special Operating Restrictions

    Science.gov (United States)

    2010-10-06

    ... ellen.crum@faa.gov . SUPPLEMENTARY INFORMATION: Background On November 30, 1999 (64 FR 66768), the FAA... Federal Aviation Administration 14 CFR Part 91 Airports/Locations: Special Operating Restrictions AGENCY... amending its airports and locations special operating restrictions regulation to clarify a...

  2. Recommendations of activity restriction in high-risk pregnancy scenarios

    DEFF Research Database (Denmark)

    Bendix, Jane; Hegaard, Hanne Kristine; Bergholt, Thomas;

    2015-01-01

    and the Danish Association of Midwives were asked to complete a tested, structured questionnaire. Results: We sent 1815 invitations; the overall response rate was 54%. A majority of clinicians recommended some form of activity restriction in the nine scenarios. The midwives recommended strict or moderate...... to the obstetricians, the midwives also reported that they expected the recommendation to be more effective. Most midwives and obstetricians reported that they thought strict activity restriction was associated with severe or moderate adverse effect, and recommended antithrombotic prophylaxis. Conclusions: Danish...... obstetricians and midwives prescribe activity restriction in most high-risk pregnancies. The degree of activity restriction and the presumed effect vary between clinicians. This may reflect different attitudes and lack of guidelines based on clinical studies of a possible benefit of activity restriction....

  3. Access to Minerals: WTO Export Restrictions and Climate Change Considerations

    Directory of Open Access Journals (Sweden)

    Stephanie Switzer

    2015-09-01

    Full Text Available In the past few years, the Chinese government opted to restrict the export of selected minerals on environmental and health grounds, subsequently leading to an uproar in countries and regions that rely heavily on imports from China to develop their renewable industry sector. This paper places the focus on the law and policy of the Chinese export restrictions of critical minerals, and its implications for the global renewables energy industry. The paper critically assesses how such export restrictions have been dealt with under the dispute settlement system of the World Trade Organisation (WTO. Drawing on this WTO jurisprudence, we posit that litigation on export restrictions of the kind imposed by China poses a threat to the legitimacy of the WTO. We therefore conclude by exploring whether there are any alternatives to litigation as a means to deal with countries choosing to impose mineral export restrictions.

  4. Quadratic Loss of Isotonic Normal Means Under Simultaneous Order Restrictions

    Institute of Scientific and Technical Information of China (English)

    马艳萍; 史宁中

    2002-01-01

    For two normal populations with unknown means μ and unknown variances σ2,assume that there are simple order restrictions among the means and variances:μ1≤μ2 and σ12≥σ22>0,This case is said to be simultaneous order restriction by Shi (Maximum likelihood estimation of means and variances from normal populations under simultaneous order restrictions.J.Multivariate,Anal.50(1994),282-293.)and an iterative algorithm of computing the order restricted maximum likelihood estimates of μi and σi2 was given in that paper,This paper shows that the restricted maximum likelihood estimate of μi has smaller mean square loss than the usual estimate xi under some conditions.

  5. Constructing Restricted Patterson Measures for Geometrically Infinite Kleinian Groups

    Institute of Scientific and Technical Information of China (English)

    Kurt FALK; Bernd O. STRATMANN

    2006-01-01

    In this paper, we study exhaustions, referred to as ρ-restrictions, of arbitrary nonelementary Kleinian groups with at most finitely many bounded parabolic elements. Special emphasis is put on the geometrically infinite case, where we obtain that the limit set of each of these Kleinian groups contains an infinite family of closed subsets, referred to as ρ-restricted limit sets, such that there in this family. Generalizing concepts which are well known in the geometrically finite case, we then introduce the notion of ρ-restricted Patterson measure, and show that these measures are non-atomic,δρ-harmonic, δρ-subconformal on special sets and δρ-conformal on very special sets. Furthermore, we obtain the results that each ρ-restriction of our Kleinian group is of δρ-divergence type and that the Hausdorff dimension of the ρ-restricted limit set is equal to δρ.

  6. Photo-Crosslinking Induced Geometric Restriction Controls the Self-Assembly of Diphenylalanine Based Peptides

    International Nuclear Information System (INIS)

    The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π — π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive 'smart' materials. (cross-disciplinary physics and related areas of science and technology)

  7. Photo-Crosslinking Induced Geometric Restriction Controls the Self-Assembly of Diphenylalanine Based Peptides

    Science.gov (United States)

    Tie, Zuo-Xiu; Qin, Meng; Zou, Da-Wei; Cao, Yi; Wang, Wei

    2011-02-01

    The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π — π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive “smart" materials.

  8. Photo-crosslinking induced geometric restriction controls the self-assembly of diphenylalanine based peptides

    International Nuclear Information System (INIS)

    The diphenylalanine (FF) motif has been widely used in the design of peptides that are capable of forming various ordered structures, such as nanotubes, nanospheres and hydrogels. In these assemblies, FF based peptides adopt an antiparallel structure and are stabilized by π-π stacking among the phenyl groups. Here we show that assembly of FF-based peptides can be controlled by their geometric restrictions. Using tripeptide FFY (L-Phe-L-Phe-L-Tyr) as an example, we demonstrate that photo-crosslinking of C-terminal tyrosine can impose a geometric restriction to the formation of an antiparallel structure, leading to a structural change of the assemblies from nanosphere to amorphous. This finding is confirmed using far-UV circular dichroism, Fourier transform infrared spectroscopy and atomic force microscopy. Based on such a mechanism, we are able to control the gel-sol transition of Fmoc-FFY using the geometric restriction induced by photo-crosslinking of C-terminal tyrosine groups. We believe that geometric restriction should be considered as an important factor in the design of peptide-based materials. It can also be implemented as a useful strategy for the construction of environment-responsive 'smart' materials. (authors)

  9. Integration of the Pleasant Events (PE) and Activity Restriction (AR) Models: Development and Validation of a “PEAR” Model of Negative Outcomes in Alzheimer’s Caregivers

    Science.gov (United States)

    Mausbach, Brent T; Roepke, Susan K; Depp, Colin A.; Moore, Raeanne; Patterson, Thomas L; Grant, Igor

    2011-01-01

    This study examined an activity restriction/pleasurable activities mismatch model for psychosocial and health-related outcomes. A total of 108 spousal caregivers of patients with Alzheimer’s Disease (AD) were assessed for their experience of social and recreational activities over the past month as well as their perception of how restricted they were for engaging in social and recreational activities. Participants were divided into three groups based on their reported activities and activity restriction: HPLR = High Pleasant Events + Low Activity Restriction (i.e., reference group; N = 28); HPHR/LPLR = Either High Pleasant Events + High Activity Restriction or Low Pleasant Events + Low Activity Restriction (N = 43); LPHR = Low Pleasant Events + High Activity Restriction (N = 37). We hypothesized that participants reporting low pleasant events combined with high activity restriction (LPHR) would demonstrate greater disturbance relative to other two groups in multiple outcome domains including: a) greater mood disturbance, b) greater use of negative coping factors, c) reduced use of positive coping strategies, d) reduced report of psychological resource factors (e.g., personal mastery, self-efficacy), and increased report of subjective health difficulties (e.g., sleep disturbance). Results generally supported our hypotheses, suggesting that assessment of both constructs is important for best predicting quality of well-being in AD caregivers, and potentially for establishing maximal effect in behavior therapy for caregivers. PMID:21292054

  10. Analysis of pressure data from a restricted-entry well in a multilayer reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, N.; Reynolds, A.C.

    1989-03-01

    This work presents new semilog type curves for analyzing data obtained at a restricted-entry well completed in a multilayer reservoir where crossflow occurs between reservoir layers. Use of the new type curves along with standard semilog analysis of pseudoradial-flow pressure data makes possible a complete analysis of pressure data. Specifically, standard semilog analysis of pseudoradial-flow pressure data yields estimates of the total flow capacity and the total skin factor. The new type curves can then be used to estimate the real mechanical skin factor resulting from damage or stimulation, the flow capacity adjacent to the open (perforated) interval, and the effective average vertical permeability.

  11. 基于河北省农民专业合作社参与的农超对接制约因素分析%Restricting Factor Analysis of Farmer Cooperatives Involved in Farmer-Supermarket Direct-Purchase Based on Hebei Province

    Institute of Scientific and Technical Information of China (English)

    闫金玲; 赵慧峰; 薛永杰

    2013-01-01

    To provide a reference for further developing farmer cooperatives,a questionnaire survey was conducted to investigate the inflating factors of farmer-supermarket direct-purchase,and the constrains were comprehensively evaluated by using econometric model.The results showed that product features and technological level were the decisive factors to achieve farmer-supermarket direct-purchase.While annual sales,logistics and distribution capabilities and product brand quality were the major factors.%为了给专业合作社的进一步发展提供参考,采用问卷方法调查了河北省农民专业合作社参与农超对接的影响因素,并运用经济计量模型对农民专业合作社参与农超对接的制约因素进行综合评价.结果表明:产品特征和技术水平是实现农超对接的决定性因素,而合作社产品的年销售额、物流配送能力和产品品牌质量是制约农民专业合作社参与农超对接的主要因素.

  12. Identification of Macroeconomic Factors in Large Panels

    DEFF Research Database (Denmark)

    Bork, Lasse; Dewachter, Hans; Houssa, Romain

    This paper presents a dynamic factor model in which the extracted factors and shocks are given a clear economic interpretation. The economic interpretation of the factors is obtained by means of a set of over-identifying loading restrictions, while the structural shocks are estimated following st...... are theoretically plausible and in line with other findings in the literature....

  13. Measurement Bias Detection through Factor Analysis

    Science.gov (United States)

    Barendse, M. T.; Oort, F. J.; Werner, C. S.; Ligtvoet, R.; Schermelleh-Engel, K.

    2012-01-01

    Measurement bias is defined as a violation of measurement invariance, which can be investigated through multigroup factor analysis (MGFA), by testing across-group differences in intercepts (uniform bias) and factor loadings (nonuniform bias). Restricted factor analysis (RFA) can also be used to detect measurement bias. To also enable nonuniform…

  14. Feeding period restriction alters the expression of peripheral circadian rhythm genes without changing body weight in mice.

    Directory of Open Access Journals (Sweden)

    Hagoon Jang

    Full Text Available Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD or a high-fat diet (HFD. In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.

  15. Life on Mars? II. Physical restrictions

    Science.gov (United States)

    Mancinelli, R. L.; Banin, A.

    1995-01-01

    The primary physical factors important to life's evolution on a planet include its temperature, pressure and radiation regimes. Temperature and pressure regulate the presence and duration of liquid water on the surface of Mars. The prolonged presence of liquid water is essential for the evolution and sustained presence of life on a planet. It has been postulated that Mars has always been a cold dry planet; it has also been postulated that early mars possessed a dense atmosphere of CO2 (> or = 1 bar) and sufficient water to cut large channels across its surface. The degree to which either of these postulates is true correlates with the suitability of Mars for life's evolution. Although radiation can destroy living systems, the high fluxes of UV radiation on the martian surface do not necessarily stop the origin and early evolution of life. The probability for life to have arisen and evolved to a significant degree on Mars, based on the postulated ranges of early martian physical factors, is almost solely related to the probability of liquid water existing on the planet for at least hundreds of millions to billions of years.

  16. Life on Mars? 2: Physical restrictions

    Science.gov (United States)

    Mancinelli, R. L.; Banin, A.

    1995-01-01

    The primary physical factors important to life's evolution on a planet include its temperature, pressure and radiation regimes. Temperature and pressure regulate the presence and duration of liquid water on the surface of Mars. The prolonged presence of liquid water is essential for the evolution and sustained presence of life on a planet. It has been postulated that Mars has always been a cold dry planet; it has also been postulated that early Mars possessed a dense atmosphere of CO2 (greater than or equal to 1 bar) and sufficient water to cut large channels across its surface. The degree to which either of these postulates is true correlates with the suitability of Mars for life's evolution. Although radiation can destroy living systems, the high fluxes of UV radiation on the martian surface do not necessarily stop the origin and early evolution of life. The probability for life to have arisen and evolved to a significant degree on Mars, based on the postulated ranges of early martian physical factors, is almost solely related to the probability of liquid water existing on the planet for at least hundreds of millions to billions of years.

  17. Effect of dietary protein restriction on renal ammonia metabolism.

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Guo, Hui; Verlander, Jill W; Weiner, I David

    2015-06-15

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

  18. Controlling pandemic flu: the value of international air travel restrictions.

    Directory of Open Access Journals (Sweden)

    Joshua M Epstein

    Full Text Available BACKGROUND: Planning for a possible influenza pandemic is an extremely high priority, as social and economic effects of an unmitigated pandemic would be devastating. Mathematical models can be used to explore different scenarios and provide insight into potential costs, benefits, and effectiveness of prevention and control strategies under consideration. METHODS AND FINDINGS: A stochastic, equation-based epidemic model is used to study global transmission of pandemic flu, including the effects of travel restrictions and vaccination. Economic costs of intervention are also considered. The distribution of First Passage Times (FPT to the United States and the numbers of infected persons in metropolitan areas worldwide are studied assuming various times and locations of the initial outbreak. International air travel restrictions alone provide a small delay in FPT to the U.S. When other containment measures are applied at the source in conjunction with travel restrictions, delays could be much longer. If in addition, control measures are instituted worldwide, there is a significant reduction in cases worldwide and specifically in the U.S. However, if travel restrictions are not combined with other measures, local epidemic severity may increase, because restriction-induced delays can push local outbreaks into high epidemic season. The per annum cost to the U.S. economy of international and major domestic air passenger travel restrictions is minimal: on the order of 0.8% of Gross National Product. CONCLUSIONS: International air travel restrictions may provide a small but important delay in the spread of a pandemic, especially if other disease control measures are implemented during the afforded time. However, if other measures are not instituted, delays may worsen regional epidemics by pushing the outbreak into high epidemic season. This important interaction between policy and seasonality is only evident with a global-scale model. Since the benefit of

  19. Analysis on the Factors which Restricting the Healthy Development of China's Sugar Industry%制约我国糖业健康发展的因素分析——以广西河池市为例

    Institute of Scientific and Technical Information of China (English)

    唐馨蕖; 覃安柳; 谭丹书

    2011-01-01

    当前,食糖价格持续上涨,除了一些导致糖价大幅波动的短期因素外,还存在防灾减灾、品种改良、蔗农增收和产业结构等方面的制约因素影响蔗糖产业长期发展,为此,本文提出了健全产业风险补偿机制、加大育种投入等建议。%Currently,sugar prices continued to rise.In addition to some short-term factors led to the volatility of sugar prices,there were also constraint factors which affected the long-term development of sugar industry,such as disaster,varieties improved,sugarcane farmers' income and industrial structure.So,this article proposed some suggestions about improving industrial risk compensation mechanism,increasing investment in breeding,etc.

  20. An Additive-Multiplicative Restricted Mean Residual Life Model

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben; Scheike, Thomas H.

    2016-01-01

    The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive-multiplicative restricted...... mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline...

  1. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  2. Company Law as a Restriction to Free Movement

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2014-01-01

    Focusing on recent judgments from the Court of Justice of the European Union, this article investigates how the notion of ‘restriction’ – which is the first step in examining whether there is an infringement of the free movement rights – is used in cases involving company law measures....... There is evidence that non-discriminatory obstacles to free movement found in company law can be restrictions. However, recent cases show that the Court may be willing to apply a more restrictive approach where only non-discriminatory measures that have a qualified deterrent effect may constitute restrictions....

  3. Study of implementation level of tobacco restriction policy in cafes and restaurants of Georgia.

    Science.gov (United States)

    Gvinianidze, K; Bakhturidze, G; Magradze, G

    2012-05-01

    Before year 2008 smoking was partially restricted in cafes and restaurants of Georgia. In 2009 Georgian Parliament adopted amendment in law "Concerning Tobacco Control" and strengthened partial restriction in cafes and restaurants, namely required that 50% of territory of those facilities must be smoke free. To observe status of implementation of tobacco control legislation in field of prohibition/restriction of smoking in cafes and restaurants conducted observation of those facilities and in-depth interviews of their owners/staff. Observation in cafes and restaurants were done in big regional centers of Georgia, namely in Tbilisi (Capital), Telavi, Kutaisi, Batumi, Rustavi, Gori, Akhaltsikhe and Zugdidi. At all 176 cafés/restaurants were observed (22,4% of all registered cafes/restaurants in Georgia). For qualitative part of the study 1-2 persons from staff of the cafe or restaurant or its owner available during the observation was interviewed. Field work was done during 2011-2012. It must be mentioned that during this period was not observed any important change in legislation and/or enforcement of smoking ban/restrictions in those facilities. Study instrument were guide for observer that contained two parts - observational and open-ended questions for owners and staff. Observation of cafes/restaurants in Georgia shows that 89,8% of them violate existing restriction on smoking. All restaurants and 85% of cafes violate the law. Only 18 (10,2%) cafes are in compliance with the legislation and all of them have total ban. Despite to the fact that more than 50% of observed cafes/restaurants were located in Tbilisi, absolute majority (88,1%) of smoke free facilities are in regions (mainly in Kutaisi, Zugdidi and Gori). Qualitative study of owners/staff of the facilities found factors that probably are influential in determination of smoking status of cafes/restaurants. Namely, decisions on those kinds of issues are made by owners according to business interest and

  4. The Role of Placental Homeobox Genes in Human Fetal Growth Restriction

    Directory of Open Access Journals (Sweden)

    Padma Murthi

    2011-01-01

    Full Text Available Fetal growth restriction (FGR is an adverse pregnancy outcome associated with significant perinatal and paediatric morbidity and mortality, and an increased risk of chronic disease later in adult life. One of the key causes of adverse pregnancy outcome is fetal growth restriction (FGR. While a number of maternal, fetal, and environmental factors are known causes of FGR, the majority of FGR cases remain idiopathic. These idiopathic FGR pregnancies are frequently associated with placental insufficiency, possibly as a result of placental maldevelopment. Understanding the molecular mechanisms of abnormal placental development in idiopathic FGR is, therefore, of increasing importance. Here, we review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic FGR. We also assess the potential for understanding transcriptional control as a means for revealing new molecular targets for the detection, diagnosis, and clinical management of idiopathic FGR.

  5. Block-based image hashing with restricted blocking strategy for rotational robustness

    Science.gov (United States)

    Xiang, Shijun; Yang, Jianquan

    2012-12-01

    Image hashing is a potential solution for image content authentication (a desired image hashing algorithm should be robust to common image processing operations and various geometric distortions). In the literature, researchers pay more attention to block-based image hashing algorithms due to their robustness to common image processing operations (such as lossy compression, low-pass filtering, and additive noise). However, the block-based hashing strategies are sensitive to rotation processing operations. This indicates that the robustness of the block-based hashing methods against rotation operations is an important issue. Towards this direction, in this article we propose a restricted blocking strategy by investigating effect of two rotation operations on an image and its blocks in both theoretical and experimental ways. Furthermore, we apply the proposed blocking strategy for the recently reported non-negative matrix factorization (NMF) hashing. Experimental results have demonstrated the validity of the block-based hashing algorithms with restricted blocking strategy for rotation operations.

  6. A comparative study on the restrictions of dynamic test methods

    Science.gov (United States)

    Majzoobi, GH.; Lahmi, S.

    2015-09-01

    Dynamic behavior of materials is investigated using different devices. Each of the devices has some restrictions. For instance, the stress-strain curve of the materials can be captured at high strain rates only with Hopkinson bar. However, by using a new approach some of the other techniques could be used to obtain the constants of material models such as Johnson-Cook model too. In this work, the restrictions of some devices such as drop hammer, Taylor test, Flying wedge, Shot impact test, dynamic tensile extrusion and Hopkinson bars which are used to characterize the material properties at high strain rates are described. The level of strain and strain rate and their restrictions are very important in examining the efficiency of each of the devices. For instance, necking or bulging in tensile and compressive Hopkinson bars, fragmentation in dynamic tensile extrusion and petaling in Taylor test are restricting issues in the level of strain rate attainable in the devices.

  7. A comparative study on the restrictions of dynamic test methods

    Directory of Open Access Journals (Sweden)

    Majzoobi GH.

    2015-01-01

    Full Text Available Dynamic behavior of materials is investigated using different devices. Each of the devices has some restrictions. For instance, the stress-strain curve of the materials can be captured at high strain rates only with Hopkinson bar. However, by using a new approach some of the other techniques could be used to obtain the constants of material models such as Johnson-Cook model too. In this work, the restrictions of some devices such as drop hammer, Taylor test, Flying wedge, Shot impact test, dynamic tensile extrusion and Hopkinson bars which are used to characterize the material properties at high strain rates are described. The level of strain and strain rate and their restrictions are very important in examining the efficiency of each of the devices. For instance, necking or bulging in tensile and compressive Hopkinson bars, fragmentation in dynamic tensile extrusion and petaling in Taylor test are restricting issues in the level of strain rate attainable in the devices.

  8. 3-restricted connectivity of graphs with given girth

    Institute of Scientific and Technical Information of China (English)

    GUO Li-tao; MENG Ji-xiang

    2008-01-01

    Let G = (V, E) be a connected graph. X C V(G) is a vertex set. X is a 3-restricted cut of G, if G-X is not connected and every component of G-X has at least three vertices. The 3-restricted connectivity k3(G) (in short k3) of G is the cardinality of a minimum 3-restricted cut of G. Χ is called κ3-cut, if Χ = κ3. A graph G is κa-connected, if a 3-restricted cut exists.Let G be a graph girth g ≥ 4, ξ3(G) is min{d(χ) + d(у) + d(z) - 4 : χуz is a 2-path of G}. It will be shown that κ3(G) = ξ3(G) under the condition of girth.

  9. United States: Funding restrictions threaten sex workers' rights.

    Science.gov (United States)

    Schleifer, Rebecca

    2005-08-01

    Recent developments concerning the US government's restrictive policies on HIV/AIDS funding have drawn attention to how the government's mandatory "anti-prostitution pledge" endangers the lives of sex workers and trafficking victims. PMID:16365969

  10. Total sleep deprivation, chronic sleep restriction and sleep disruption.

    Science.gov (United States)

    Reynolds, Amy C; Banks, Siobhan

    2010-01-01

    Sleep loss may result from total sleep deprivation (such as a shift worker might experience), chronic sleep restriction (due to work, medical conditions or lifestyle) or sleep disruption (which is common in sleep disorders such as sleep apnea or restless legs syndrome). Total sleep deprivation has been widely researched, and its effects have been well described. Chronic sleep restriction and sleep disruption (also known as sleep fragmentation) have received less experimental attention. Recently, there has been increasing interest in sleep restriction and disruption as it has been recognized that they have a similar impact on cognitive functioning as a period of total sleep deprivation. Sleep loss causes impairments in cognitive performance and simulated driving and induces sleepiness, fatigue and mood changes. This review examines recent research on the effects of sleep deprivation, restriction and disruption on cognition and neurophysiologic functioning in healthy adults, and contrasts the similarities and differences between these three modalities of sleep loss.

  11. Miscarriage and early first trimester growth restriction by ultrasound

    Directory of Open Access Journals (Sweden)

    Neelima Agarwal

    2016-05-01

    Conclusions: CRL was significantly smaller in pregnancies that subsequently ended in miscarriage. This suggests that early first trimester growth restriction is associated with subsequent intrauterine death. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1558-1561

  12. Personal paths of fluid restriction in patients on hemodialysis.

    Science.gov (United States)

    Tovazzi, Maria Elena; Mazzoni, Valentina

    2012-01-01

    The aim of this study was to explore the perspectives of patients on hemodialysis about their experience of fluid restriction. Qualitative interviews were conducted to grasp the patients' lived experience, and from a phenomenological analysis, several categories emerged that describe patients' understanding. Three themes in particular from patients' experiences are described and discussed because of their relevance for health professionals. These include (a) fluid restriction introduces the perception of individuals to see themselves as addicts who deal with a constant inner conflict, (b) the difficulty in finding the right boundaries between common sense and scientific knowledge about fluid restriction, and (c) the role of personal motivations and willingness in pursuit of compliance. Recognizing the force of personal meaning for individuals with renal disease will support health professionals to help patients in pursuing the regime of fluid restriction. PMID:22866360

  13. HCUP State Emergency Department Databases (SEDD) - Restricted Access File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The State Emergency Department Databases (SEDD) contain the universe of emergency department visits in participating States. Restricted access data files are...

  14. Grout Treatment Facility Land Disposal Restriction Management Plan

    International Nuclear Information System (INIS)

    This document establishes management plans directed to result in the land disposal of grouted wastes at the Hanford Grout Facilities in compliance with Federal, State of Washington, and Department of Energy land disposal restrictions. 9 refs., 1 fig

  15. Caloric restriction and Metabolism in Lean and Obese rats.

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data related to obese and lean strains of rat commonly used in the laboratory that are calorically restricted and its effects on physiologic parameters (Body...

  16. Flow-test device fits into restricted access passages

    Science.gov (United States)

    Fitzgerald, J. J.; Oberschmidt, M.; Rosenbaum, B. J.

    1967-01-01

    Test device using a mandrel with a collapsible linkage assembly enables a fluid flow sensor to be properly positioned in a restricted passage by external manipulation. This device is applicable to the combustion chamber of a rocket motor.

  17. 48 CFR 225.7012 - Restriction on supercomputers.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on supercomputers. 225.7012 Section 225.7012 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... supercomputers....

  18. Dynamic Factor Models for the Volatility Surface

    DEFF Research Database (Denmark)

    van der Wel, Michel; Ozturk, Sait R.; Dijk, Dick van

    -based models are both rejected against the general dynamic factor model, (ii) the factors driving the surface are highly persistent, (iii) for the restricted models option Delta is preferred over the more often used strike relative to spot price as measure for moneyness.......The implied volatility surface is the collection of volatilities implied by option contracts for different strike prices and time-to-maturity. We study factor models to capture the dynamics of this three-dimensional implied volatility surface. Three model types are considered to examine desirable...... features for representing the surface and its dynamics: a general dynamic factor model, restricted factor models designed to capture the key features of the surface along the moneyness and maturity dimensions, and in-between spline-based methods. Key findings are that: (i) the restricted and spline...

  19. Pig kidney legumain: an asparaginyl endopeptidase with restricted specificity.

    Science.gov (United States)

    Dando, P M; Fortunato, M; Smith, L; Knight, C G; McKendrick, J E; Barrett, A J

    1999-01-01

    Legumain was recently discovered as a lysosomal endopeptidase in mammals [Chen, Dando, Rawlings, Brown, Young, Stevens, Hewitt, Watts and Barrett (1997) J. Biol. Chem. 272, 8090-8098], having been known previously only from plants and invertebrates. It has been shown to play a key role in processing of the C fragment of tetanus toxin for presentation by the MHC class-II system [Manoury, Hewitt, Morrice, Dando, Barrett and Watts (1998) Nature (London) 396, 695-699]. We examine here the specificity of the enzyme from pig kidney by use of protein, oligopeptide and synthetic arylamide substrates, all determinations being made at pH 5.8. In proteins, only about one in ten of the asparaginyl bonds were hydrolysed, and these were mostly predicted to be located at turns on the protein surface. Bonds that were not cleaved in tetanus toxin were cleaved when presented in oligopeptides, sometimes faster than an equivalent oligopeptide based on a bond that was cleaved in the protein. Legumain cleaved the bait region of rat alpha1-macroglobulin and was 'trapped' by the macroglobulin, as most other endopeptidases are, but did not interact with human alpha2-macroglobulin, which contains no asparagine residue in its bait region. Glycosylation of asparagine totally prevented hydrolysis by legumain. Specificity for arylamide substrates was evaluated with reference to benzyloxycarbonyl-Ala-Ala-Asn-aminomethylcoumarin, and the preference for the P3-position amino acid was Ala>Tyr(tertiary butyl)>Val>Pro>Phe=Tyr>Leu=Gly. There was no hydrolysis of substrate analogues containing mono- or di-N-methylasparagines, l-2-amino-3-ureidopropionic acid or citrulline in the P1 position. We conclude that mammalian legumain appears to be totally restricted to the hydrolysis of asparaginyl bonds in substrates of all kinds. There seem to be no strong preferences for particular amino acids in other subsites, and yet there are still unidentified factors that prevent hydrolysis of many asparaginyl bonds

  20. Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures.

    Directory of Open Access Journals (Sweden)

    Marissa J Schafer

    Full Text Available Calorie restriction (CR enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan. However, the mosaic of molecular changes responsible for CR benefits remains unclear, particularly in brain regions susceptible to deterioration during aging. We examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer's disease (AD. Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses age-dependent signatures of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP, and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger-adult (5 months, 2.5 months of feeding and older-adult (15 months, 12.5 months of feeding timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa protein 1b (Hspa1b and heat shock 70 kDa protein 5 (Hspa5, protein disulfide isomerase family A member 4 (Pdia4 and protein disulfide isomerase family A member 6 (Pdia6, and calreticulin (Calr. Expression levels of putative neuroprotective factors, klotho (Kl and transthyretin (Ttr, are also elevated by CR in adulthood, although the global CR-specific expression profiles at younger and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within the hippocampal CA1 sector.

  1. Fate of diffusion restricted lesions in acute intracerebral hemorrhage.

    Directory of Open Access Journals (Sweden)

    Yuan-Hsiung Tsai

    Full Text Available Diffusion-restricted lesions on diffusion-weighted imaging (DWI are detected in patients with intracerebral hemorrhage (ICH. In this study, we aimed to determine the fate of DWI lesions in ICH patients and whether the presence of DWI lesions is associated with functional outcome in patients with ICH.This prospective study enrolled 153 patients with acute ICH. Baseline MRI scans were performed within 2 weeks after ICH to detect DWI lesions and imaging markers for small vessel disease (SVD. Follow-up MRI scans were performed at 3 months after ICH to assess the fate of the DWI lesions. We analyzed the associations between the characteristics of DWI lesions with clinical features and functional outcome.Seventeen of the 153 patients (11.1% had a total of 25 DWI lesions. Factors associated with DWI lesions were high initial systolic and mean arterial blood pressure (MAP at the emergency room, additional lowering of MAP within 24 hours, and the presence of white matter hyperintensity and cerebral microbleeds. Thirteen of the 25 DWI lesions (52% were not visible on follow-up T2-weighted or fluid-attenuated inversion recovery images and were associated with high apparent diffusion coefficient value and a sharper decease in MAP. The regression of DWI lesions was associated with good functional outcome.More than half of the DWI lesions in the ICH patients did not transition to visible, long-term infarction. Only if the DWI lesion finally transitioned to final infarction was a poor functional outcome predicted. A DWI lesion may be regarded as an ischemic change of SVD and does not always indicate certain cerebral infarction or permanent tissue injury.

  2. Economic effects of western Federal land-use restrictions on U.S. coal markets

    Science.gov (United States)

    Watson, William Downing; Medlin, A.L.; Krohn, K.K.; Brookshire, D.S.; Bernknopf, R.L.

    1991-01-01

    Current regulations on land use in the Western United States affect access to surface minable coal resources. This U.S. Geological Survey study analyzes the long-term effects of Federal land-use restrictions on the national cost of meeting future coal demands. The analysis covers 45 years. The U.S. Bureau of Land Management has determined the environmental, aesthetic, and economic values of western Federal coal lands and has set aside certain areas from surface coal mining to protect other valued land uses, including agricultural, environmental, and aesthetic uses. Although there are benefits to preserving natural areas and to developing areas for other land uses, these restrictions produce long-term national and regional costs that have not been estimated previously. The Dynamic Coal Allocation Model integrates coal supply (coal resource tonnage and coal quality by mining cost for 60 coal supply regions) with coal demand (in 243 regions) for the entire United States. The model makes it possible to evaluate the regional economic impacts of coal supply restrictions wherever they might occur in the national coal market. The main factors that the economic methodology considers are (1) coal mining costs, (2) coal transportation costs, (3) coal flue gas desulfurization costs, (4) coal demand, (5) regulations to control sulfur dioxide discharges, and (6) specific reductions in coal availability occurring as a result of land-use restrictions. The modeling system combines these economic factors with coal deposit quantity and quality information--which is derived from the U.S. Geological Survey's National Coal Resources Data System and the U.S. Department of Energy's Demonstrated Reserve Base--to determine a balance between supply and demand so that coal is delivered at minimum cost.

  3. Design of a factorial experiment with randomization restrictions to assess medical device performance on vascular tissue

    Directory of Open Access Journals (Sweden)

    Pinnell Margaret F

    2011-05-01

    Full Text Available Abstract Background Energy-based surgical scalpels are designed to efficiently transect and seal blood vessels using thermal energy to promote protein denaturation and coagulation. Assessment and design improvement of ultrasonic scalpel performance relies on both in vivo and ex vivo testing. The objective of this work was to design and implement a robust, experimental test matrix with randomization restrictions and predictive statistical power, which allowed for identification of those experimental variables that may affect the quality of the seal obtained ex vivo. Methods The design of the experiment included three factors: temperature (two levels; the type of solution used to perfuse the artery during transection (three types; and artery type (two types resulting in a total of twelve possible treatment combinations. Burst pressures of porcine carotid and renal arteries sealed ex vivo were assigned as the response variable. Results The experimental test matrix was designed and carried out as a split-plot experiment in order to assess the contributions of several variables and their interactions while accounting for randomization restrictions present in the experimental setup. The statistical software package SAS was utilized and PROC MIXED was used to account for the randomization restrictions in the split-plot design. The combination of temperature, solution, and vessel type had a statistically significant impact on seal quality. Conclusions The design and implementation of a split-plot experimental test-matrix provided a mechanism for addressing the existing technical randomization restrictions of ex vivo ultrasonic scalpel performance testing, while preserving the ability to examine the potential effects of independent factors or variables. This method for generating the experimental design and the statistical analyses of the resulting data are adaptable to a wide variety of experimental problems involving large-scale tissue-based studies of

  4. Status of selected nutrients in obese dogs undergoing caloric restriction

    OpenAIRE

    Linder, Deborah E; Freeman, Lisa M.; Holden, Shelley L; Biourge, Vincent; German, Alexander J.

    2013-01-01

    Background The purpose of this study was to test the hypothesis that dog plasma concentrations of selected nutrients decrease after undergoing caloric restriction for weight loss. Thirty-one overweight dogs that had successfully lost at least 15% of initial body weight were included in the study. Nutrients that had been previously identified to be at potential risk of deficiency during caloric restriction were measured in plasma (choline, amino acids) and urine (selenium) at the initiation an...

  5. Insights into restrictive cardiomyopathy from clinical and animal studies

    OpenAIRE

    Jean-Charles, Pierre-Yves; Li, Yue-Jin; Nan, Chang-Long; Huang, Xu-Pei

    2011-01-01

    Cardiomyopathies are diseases that primarily affect the myocardium, leading to serious cardiac dysfunction and heart failure. Out of the three major categories of cardiomyopathies (hypertrophic, dilated and restrictive), restrictive cardiomyopathy (RCM) is less common and also the least studied. However, the prognosis for RCM is poor as some patients dying in their childhood. The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is...

  6. Conforming restricted Delaunay mesh generation for piecewise smooth complexes

    OpenAIRE

    Engwirda, Darren

    2016-01-01

    A Frontal-Delaunay refinement algorithm for mesh generation in piecewise smooth domains is described. Built using a restricted Delaunay framework, this new algorithm combines a number of novel features, including: (i) a consistent, conforming restricted Delaunay representation for domains specified as a (non-manifold) collection of piecewise smooth surface patches and curve constraints, (ii) a `protection' strategy for domains containing 1-dimensional features that meet at sharply acute angle...

  7. Supporting several levels of restriction in the UML

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Damm, Christian Heide; Thomsen, Michael;

    2000-01-01

    The emergence of the Unified Modeling Language (UML) has provided software developers with an effective and efficient shared language. However, UML is often too restrictive in initial, informal, and creative modelling, and it is in some cases not restrictive enough, e.g., for code generation. Based....... This approach potentially increases the usability of the UML, and thus ultimately leads to greater quality and adoption of UML models....

  8. Restriction Enzyme Digestion Exercise – An In-class Activity

    OpenAIRE

    Michelle Parent

    2010-01-01

    Understanding the concepts of molecular biology and then applying those concepts to laboratory experiments can be challenging to entry-level students. In order to facilitate the topics of restriction enzyme digestion and the generation of compatible ends in the process of gene cloning, an in-class activity was designed. This restriction enzyme digestion exercise, designed for an introductory undergraduate course in genetics, molecular biology and molecular diagnostics, can be utilized ...

  9. Quons Restricted to the Antisymmetric Subspace Formalism and Applications

    CERN Document Server

    Avancini, S S; Marinelli, J R; Peres-Menezes, D; Watanabe de Moraes, M M

    2003-01-01

    In this work we develop a formalism to treat quons restricted to the antisymmetric part of their many-body space. A model in which a system of identical quons interact through a pairing force is then solved within this restriction and the differences between our solution and the usual fermionic model solution are then presented and discussed in detail. Possible connections to physical systems are also considered.

  10. Benefits of short-term dietary restriction in mammals

    OpenAIRE

    Robertson, Lauren T.; Mitchell, James R.

    2013-01-01

    Dietary or calorie restriction (DR, CR), defined as reduced food intake without malnutrition, imparts many benefits in model organisms. Extended longevity is the most popularized benefit but the least clinically relevant due to the requirement for long-term food restriction. DR also promotes stress resistance and metabolic fitness. Emerging data in experimental models and in humans indicate that these benefits occur rapidly upon initiation of DR, suggesting potential clinical relevance. Here ...

  11. Unintended Pregnancies, Restrictive Abortion Laws, and Abortion Demand

    OpenAIRE

    Medoff, Marshall H.

    2012-01-01

    This study examines the effect restrictive state abortion laws have on the pregnancy resolution decisions of women with unintended pregnancies. The empirical results find that the abortion ratio and the abortion rate of unintended pregnancies are more sensitive to increases in the abortion price than previous estimates that analyzed total pregnancies (unintended and intended). A Medicaid funding restriction has very little effect on a state's abortion rate of unintended pregnancies, but cause...

  12. IS-linked movement of a restriction-modification system.

    Directory of Open Access Journals (Sweden)

    Noriko Takahashi

    Full Text Available Potential mobility of restriction-modification systems has been suggested by evolutionary/bioinformatic analysis of prokaryotic genomes. Here we demonstrate in vivo movement of a restriction-modification system within a genome under a laboratory condition. After blocking replication of a temperature-sensitive plasmid carrying a PaeR7I restriction-modification system in Escherichia coli cells, the plasmid was found integrated into the chromosome of the surviving cells. Sequence analysis revealed that, in the majority of products, the restriction-modification system was linked to chromosomal insertion sequences (ISs. Three types of products were: (I apparent co-integration of the plasmid and the chromosome at a chromosomal IS1 or IS5 copy (24/28 analyzed; (II de novo insertion of IS1 with the entire plasmid except for a 1-3 bp terminal deletion (2/28; and (III reciprocal crossing-over between the plasmid and the chromosome involving 1-3 bp of sequence identity (2/28. An R-negative mutation apparently decreased the efficiency of successful integration by two orders of magnitude. Reconstruction experiments demonstrated that the restriction-dependence was mainly due to selection against cells without proper integration: their growth was inhibited by the restriction enzyme action. These results demonstrate collaboration of a mobile element and a restriction-modification system for successful joint migration. This collaboration may have promoted the spread and, therefore, the long-term persistence of these complexes and restriction-modification systems in a wide range of prokaryotes.

  13. Cornering the market: restriction of retail supermarket locations

    OpenAIRE

    Nairne Cameron; Carl G Amrhein; Karen E Smoyer-Tomic; Raine, Kim D; Lee Yen Chong

    2010-01-01

    A major source of healthy foods, North American supermarkets have become larger in recent years, with new stores opening and older stores closing. Upon closure, there is evidence of some supermarket sites being placed under restrictive covenants, a practice that restricts future use of the site. The purpose is usually to limit food sales at the location, thus minimizing competition for a chain’s nearby stores. In Edmonton, Alberta eighteen covenants have been documented on former supermarket ...

  14. Personnel Tour Scheduling When Starting-Time Restrictions Are Present

    OpenAIRE

    Michael J. Brusco; Larry W. Jacobs

    1998-01-01

    This paper presents an effective solution strategy for an important category of personnel scheduling problems. Specifically, we address the restricted starting-time tour-scheduling problem (RSTP), which involves the determination of the hours of the day (shifts) and days of the week (days on) that employees are assigned to work. RSTP is characterized by restrictions on the number of daily time periods in which employees may begin their shifts. Moreover, the RSTP we consider contains constrain...

  15. Animal models of restricted repetitive behavior in autism

    OpenAIRE

    Lewis, Mark H.; Tanimura, Yoko; Lee, Linda W.; Bodfish, James W.

    2006-01-01

    Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather t...

  16. Agricultural Production Restrictions and Market Power: An Antitrust Analysis

    OpenAIRE

    Bolotova, Yuliya

    2015-01-01

    During the recent decade the organizations of agricultural producers in the national dairy, potato, egg and mushroom industries implemented various pre-production and production restriction practices with the primary objective of agricultural output price stabilization. The buyers of the affected agricultural commodities have challenged the legal status of production restrictions in a number of recent and current antitrust lawsuits, arguing that the Capper-Volstead Act, a limited antitrust ex...

  17. Advanced Mean Field Theory of Restricted Boltzmann Machine

    OpenAIRE

    Huang, Haiping; Toyoizumi, Taro

    2015-01-01

    Learning in restricted Boltzmann machine is typically hard due to the computation of gradients of log-likelihood function. To describe the network state statistics of the restricted Boltzmann machine, we develop an advanced mean field theory based on the Bethe approximation. Our theory provides an efficient message passing based method that evaluates not only the partition function (free energy) but also its gradients without requiring statistical sampling. The results are compared with those...

  18. Identification of leptospiral isolates by bacterial restriction endonuclease analysis (Brenda

    Directory of Open Access Journals (Sweden)

    Venkatesha M

    2001-01-01

    Full Text Available DNA samples from 19 reference serovars belonging to 19 different serogroups of Leptospira interrogans and two serovars belonging to Leptospira biflexa were examined by bacterial restriction endonuclease analysis using EcoR I and Hae III enzymes. All the serovars gave unique restriction patterns that differed from each other. DNA from 10 local isolates digested with these enzymes produced patterns which on comparison with the standard patterns produced by reference strains could be identified to serovar level.

  19. Chronic Maternal Dietary Chromium Restriction Modulates Visceral Adiposity

    OpenAIRE

    Padmavathi, Inagadapa J.N.; Rao, K Rajender; Venu, Lagishetty; Ganeshan, Manisha; Kumar, K. Anand; Rao, Ch. Narasima; Harishankar, Nemani; Ismail, Ayesha; Raghunath, Manchala

    2009-01-01

    OBJECTIVE We demonstrated previously that chronic maternal micronutrient restriction altered the body composition in rat offspring and may predispose offspring to adult-onset diseases. Chromium (Cr) regulates glucose and fat metabolism. The objective of this study is to determine the long-term effects of maternal Cr restriction on adipose tissue development and function in a rat model. RESEARCH DESIGN AND METHODS Female weanling WNIN rats received, ad libitum, a control diet or the same with ...

  20. Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF.

    Science.gov (United States)

    Pogenberg, Vivian; Ogmundsdóttir, Margrét H; Bergsteinsdóttir, Kristín; Schepsky, Alexander; Phung, Bengt; Deineko, Viktor; Milewski, Morlin; Steingrímsson, Eiríkur; Wilmanns, Matthias

    2012-12-01

    Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and an important oncogene in melanoma. MITF heterodimeric assembly with related basic helix-loop-helix leucine zipper transcription factors is highly restricted, and its binding profile to cognate DNA sequences is distinct. Here, we determined the crystal structure of MITF in its apo conformation and in the presence of two related DNA response elements, the E-box and M-box. In addition, we investigated mouse and human Mitf mutations to dissect the functional significance of structural features. Owing to an unusual three-residue shift in the leucine zipper register, the MITF homodimer shows a marked kink in one of the two zipper helices to allow an out-of-register assembly. Removal of this insertion relieves restricted heterodimerization by MITF and permits assembly with the transcription factor MAX. Binding of MITF to the M-box motif is mediated by an unusual nonpolar interaction by Ile212, a residue that is mutated in mice and humans with Waardenburg syndrome. As several related transcription factors have low affinity for the M-box sequence, our analysis unravels how these proteins discriminate between similar target sequences. Our data provide a rational basis for targeting MITF in the treatment of important hereditary diseases and cancer. PMID:23207919