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Sample records for cd81 gene defect

  1. CD81-induced behavioural changes during chronic cocaine administration: in vivo gene delivery with regulatable lentivirus

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    Bahi, Amine; Boyer, Frederic; Kafri, Tal; Dreyer, Jean-luc

    2005-01-01

    CD81, a tetraspanin transmembrane protein involved in cell adhesion, is up-regulated in the mesolimbic dopaminergic pathway 24 h following acute administration of high doses of cocaine [Brenz-Verca et al., (2001) Mol. Cell. Neurosci., 17, 303-316]. Further evidence consecutive with this observation and based on microarray analysis are presented here. In addition, a regulatable lentivirus was developed bearing the rat CD81 gene under the control of a tetracycline inducible system. This lentivi...

  2. MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma

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    Skiriute Daina

    2012-06-01

    Full Text Available Abstract Background Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome. Methods The methylation status of MGMT, CD81, GATA6, DR4, and CASP8 in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis. Results The overwhelming majority (97.3% of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: MGMT in 51.3%, GATA6 in 68.4%, CD81 in 46.1%, DR4 in 41.3% and CASP8 in 56.8% of tumors. Methylation of MGMT was associated with younger patient age (p CASP8 with older (p MGMT methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p CASP8 was more frequent in patients who survived shorter than 36 months (p MGMT, GATA6 and CASP8 as independent predictors for glioblastoma patient outcome (p MGMT and GATA6 were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy. Conclusions High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of MGMT, GATA6 and CASP8 genes methylation in glioblastoma patient outcome.

  3. Male CD81 Knockout Genotype Disrupts Mendelian Distribution of Offspring

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    Mordica, Whitney J.; Gallagher, Ryan J; Kennedy, Jenna L; Chapes, Stephen K.

    2010-01-01

    CD81 is an integral membrane protein in the tetraspanin superfamily that serves as an adaptor protein. CD81 is also a maternally imprinted gene that is found in a regulated cluster of genes on mouse chromosome 7. Among offspring produced from heterozygous breeding pairs, CD81null/null mice grew at the same rate as CD81+/+ and CD81+/null mice. Because of an inhibition in sperm–egg fusion, CD81null/null female mice are much less fertile than CD81+/+ and CD81+/null mice. However, no published st...

  4. CD81 and CD9 work independently as extracellular components upon fusion of sperm and oocyte

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    Naoko Ohnami

    2012-05-01

    When a sperm and oocyte unite into one cell upon fertilization, membranous fusion between the sperm and oocyte occurs. In mice, Izumo1 and a tetraspanin molecule CD9 are required for sperm-oocyte fusion as one of the oocyte factors, and another tetraspanin molecule CD81 is also thought to involve in this process. Since these two tetraspanins often form a complex upon cell-cell interaction, it is probable that such a complex is also formed in sperm-oocyte interaction; however, this possibility is still under debate among researchers. Here we assessed this problem using mouse oocytes. Immunocytochemical analysis demonstrated that both CD9 and CD81 were widely distributed outside the oocyte cell membrane, but these molecules were separate, forming bilayers, confirmed by immunobiochemical analysis. Electron-microscopic analysis revealed the presence of CD9- or CD81-incorporated extracellular structures in those bilayers. Finally, microinjection of in vitro-synthesized RNA showed that CD9 reversed a fusion defect in CD81-deficient oocytes in addition to CD9-deficient oocytes, but CD81 failed in both oocytes. These results suggest that both CD9 and CD81 independently work upon sperm-oocyte fusion as extracellular components.

  5. CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cells.

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    Gensert, JoAnn M; Baranova, Oxana V; Weinstein, David E; Ratan, Rajiv R

    2007-06-01

    Recent advances in cancer cell biology have focused on histone deacetylase inhibitors (HDACi's) because they target pathways critical to the development and progression of disease. In particular, HDACi's can induce expression of epigenetically silenced genes that promote growth arrest, differentiation and cell death. In glioma cells, one such repressed gene is the tetraspanin CD81, which regulates cytostasis in various cell lines and in astrocytes, the major cellular component of gliomas. Our studies show that HDACi's, trichostatin and sodium butyrate, promote growth arrest and differentiation with negligible cell death in glioma cells and induce expression of CD81 and cyclin-dependent kinase inhibitor 1A (p21(CIP/WAF-1)), another regulator of cytostasis in astrocytes. Interference RNA knock-down of CD81 abrogates cytostasis promoted by HDAC inhibition indicating that HDACi-induced CD81 is responsible for growth arrest. Induction of CD81 expression through HDAC inhibition is a novel strategy to promote growth arrest in glioma cells.

  6. Active RNA replication of hepatitis C virus downregulates CD81 expression.

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    Po-Yuan Ke

    Full Text Available So far how hepatitis C virus (HCV replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp infection and downregulated cell surface level of CD81, a critical HCV entry (coreceptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  7. The swine CD81 enhances E2-based DNA vaccination against classical swine fever.

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    Li, Wenliang; Mao, Li; Zhou, Bin; Liu, Xia; Yang, Leilei; Zhang, Wenwen; Jiang, Jieyuan

    2015-07-01

    Classical swine fever (CSF) is a highly contagious and economically important viral disease that affects the pig industry worldwide. The glycoprotein E2 of CSFV can induce neutralizing antibodies and protective immunity, and is widely used for novel vaccine development. The objective of this study was to explore whether a tetraspanin molecule CD81 could improve the immune responses of an E2-based DNA vaccine. Plasmids pVAX-CD81, pVAX-E2 and pVAX-CD81-E2 were constructed and the expression of target proteins was confirmed in BHK-21 cells by indirect immunofluorescence assay. BALB/c mice were divided into 5 groups and immunized with different plasmids (pVAX-E2, pVAX-CD81-E2, pVAX-E2+pVAX-CD81, pVAX-CD81 and PBS) three times with two weeks interval. The results showed that the introduction of CD81 promoted higher humoral and cellular immune responses than E2 expression alone (P<0.05). In addition, immunization with pVAX-CD81-E2 induced stronger immune responses than pVAX-E2+pVAX-CD81. Furthermore, four groups of pigs were immunized with pVAX-E2, pVAX-CD81-E2, pVAX-CD81 and PBS, respectively. Humoral and cellular immune responses detection showed similar results with those in mice. Compared to pVAX-E2, pVAX-CD81-E2 induced higher titers of neutralizing antibodies after viral challenge and conferred stronger protection. These results confirmed the capacity of swine CD81 enhancing the humoral and cellular responses with an adjuvant effect on CSFV DNA vaccine. This is the first report demonstrating the adjuvant effect of CD81 to enhance the DNA vaccination for swine pathogen. PMID:26051512

  8. Engagement of CD81 induces ezrin tyrosine phosphorylation and its cellular redistribution with filamentous actin

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    Coffey, Greg P.; Rajapaksa, Ranjani; Liu, Raymond; Sharpe, Orr; Kuo, Chiung-Chi; Wald Krauss, Sharon; Sagi, Yael; Davis, R. Eric; Staudt, Louis M.; Sharman, Jeff P.; Robinson, William H.; Levy, Shoshana

    2009-06-09

    CD81 is a tetraspanin family member involved in diverse cellular interactions in the immune and nervous systems and in cell fusion events. However, the mechanism of action of CD81 and of other tetraspanins has not been defined. We reasoned that identifying signaling molecules downstream of CD81 would provide mechanistic clues. We engaged CD81 on the surface of Blymphocytes and identified the induced tyrosine-phosphorylated proteins by mass spectrometry. This analysis showed that the most prominent tyrosine phosphorylated protein was ezrin, an actin binding protein and a member of the ezrin-radixin-moesin family. We also found that CD81 engagement induces spleen tyrosine kinase (Syk) and that Syk was involved in tyrosine phosphorylation of ezrin. Ezrin colocalized with CD81 and F-actin upon stimulation and this association was disrupted when Syk activation was blocked. Taken together, these studies suggest a model in which CD81 interfaces between the plasma membrane and the cytoskeleton by activating Syk, mobilizing ezrin, and recruiting F-actin to facilitate cytoskeletal reorganization and cell signaling. This may be a mechanism explaining the pleiotropic effects induced in response to stimulating cells by anti-CD81 antibodies or by the hepatitis C virus, which uses this molecule as its key receptor.

  9. Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice

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    Fei Yan

    2015-01-01

    Full Text Available The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein- targeted microparticles of iron oxide (CD81-MPIO for magnetic resonance imaging (MRI of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G- MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81-MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P<0.01. Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging.

  10. A Role for CD81 and Hepatitis C Virus in Hepatoma Mobility

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    Claire L. Brimacombe

    2014-03-01

    Full Text Available Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC is an increasing global health burden, in part due to the increasing prevalence of hepatitis C virus (HCV associated HCC. The tetraspanin CD81 is an essential receptor for HCV, however, its role in hepatoma biology is uncertain. We demonstrate that antibody engagement of CD81 promotes hepatoma spread, which is limited by HCV infection, in an actin-dependent manner and identify an essential role for the C-terminal interaction with Ezrin-Radixin-Moesin (ERM proteins in this process. We show enhanced hepatoma migration and invasion following expression of CD81 and a reduction in invasive potential upon CD81 silencing. In addition, we reveal poorly differentiated HCC express significantly higher levels of CD81 compared to adjacent non-tumor tissue. In summary, these data support a role for CD81 in regulating hepatoma mobility and propose CD81 as a tumour promoter.

  11. CD81 Inhibits the Proliferation of Astrocytes by Inducing G_0/G_1 Arrest In Vitro

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    马俊芳; 刘仁刚; 彭会明; 周洁萍; 李海朋

    2010-01-01

    Astrocytes play a major role in the reactive processes in response to neuronal injuries in the brain.Excessive gliosis is detrimental and can contribute to neuronal damage.CD81(TAPA),a member of the tetraspanin family of proteins,is upregulated by astrocytes after traumatic injury to the rat central nervous system(CNS).To further understand the role of CD81 in the inhibition of astrocytes,we analyzed the effects of a CD81 antibody,on cultured rat astrocytes.The results indicated that the effect worked in a ...

  12. Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

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    Zhan-Fei Tian; Hong Shen; Xi-Hua Fu; Yi-Chun Chen; Hubert E Blum; Thomas F Baumert; Xi-Ping Zhao

    2009-01-01

    AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.

  13. The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry

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    Rubinstein Eric

    2009-05-01

    Full Text Available Abstract Background Three percent of the world's population is chronically infected with hepatitis C virus (HCV and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Interestingly, CD81 is also required for Plasmodium infection. A major characteristic of tetraspanins is their ability to interact with each other and other transmembrane proteins to build tetraspanin-enriched microdomains (TEM. Results In our study, we describe a human hepatoma Huh-7 cell clone (Huh-7w7 which has lost CD81 expression and can be infected by HCV when human CD81 (hCD81 or mouse CD81 (mCD81 is ectopically expressed. We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w mAbs to analyze the role of TEM-associated CD81 in HCV infection. Importantly, MT81w antibody, which only recognizes TEM-associated mCD81, did not strongly affect HCV infection. Furthermore, cholesterol depletion, which inhibits HCV infection and reduces total cell surface expression of CD81, did not affect TEM-associated CD81 levels. In addition, sphingomyelinase treatment, which also reduces HCV infection and cell surface expression of total CD81, raised TEM-associated CD81 levels. Conclusion In contrast to Plasmodium infection, our data show that association of CD81 with TEM is not essential for the early steps of HCV life cycle, indicating that these two pathogens, while using the same molecules, invade their host by different mechanisms.

  14. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

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    Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi, E-mail: tajima@nirs.go.jp

    2014-04-18

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.

  15. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

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    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation

  16. CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells.

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    Witteveldt, Jeroen; Evans, Matthew J; Bitzegeio, Julia; Koutsoudakis, George; Owsianka, Ania M; Angus, Allan G N; Keck, Zhen-Yong; Foung, Steven K H; Pietschmann, Thomas; Rice, Charles M; Patel, Arvind H

    2009-01-01

    Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1(DeltaE1E2)-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1(W529A) was unaffected by the presence of neutralizing antibodies that inhibit E2-CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission. PMID:19088272

  17. Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

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    Ashfaq Usman A

    2011-11-01

    Full Text Available Abstract Background HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. Methods and result The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells. Conclusion Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.

  18. Identification of ligands that target the HCV-E2 binding site on CD81.

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    Olaby, Reem Al; Azzazy, Hassan M; Harris, Rodney; Chromy, Brett; Vielmetter, Jost; Balhorn, Rod

    2013-04-01

    Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.

  19. CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies

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    Laetitia Zona

    2014-02-01

    Full Text Available Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas, CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection.

  20. HIV-1 Entry and Trans-Infection of Astrocytes Involves CD81 Vesicles

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    Gray, Lachlan R.; Turville, Stuart G.; HItchen, Tina L.; Cheng, Wan-Jung; Ellett, Anne M.; Salimi, Hamid; Roche, Michael J.; Wesselingh, Steve L.; Gorry, Paul R.; Churchill, Melissa J.

    2014-01-01

    Astrocytes are extensively infected with HIV-1 in vivo and play a significant role in the development of HIV-1-associated neurocognitive disorders. Despite their extensive infection, little is known about how astrocytes become infected, since they lack cell surface CD4 expression. In the present study, we investigated the fate of HIV-1 upon infection of astrocytes. Astrocytes were found to bind and harbor virus followed by biphasic decay, with HIV-1 detectable out to 72 hours. HIV-1 was observed to associate with CD81-lined vesicle structures. shRNA silencing of CD81 resulted in less cell-associated virus but no loss of co-localization between HIV-1 and CD81. Astrocytes supported trans-infection of HIV-1 to T-cells without de novo virus production, and the virus-containing compartment required 37°C to form, and was trypsin-resistant. The CD81 compartment observed herein, has been shown in other cell types to be a relatively protective compartment. Within astrocytes, this compartment may be actively involved in virus entry and/or spread. The ability of astrocytes to transfer virus, without de novo viral synthesis suggests they are capable of sequestering and protecting virus and thus, they could potentially facilitate viral dissemination in the CNS. PMID:24587404

  1. Soluble Serum CD81 Is Elevated in Patients with Chronic Hepatitis C and Correlates with Alanine Aminotransferase Serum Activity

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    Welker, Martin-Walter; Reichert, David; Susser, Simone; Sarrazin, Christoph; Martinez, Yolanda; Herrmann, Eva; Zeuzem, Stefan; Piiper, Albrecht; Kronenberger, Bernd

    2012-01-01

    Aim Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity. Patients and Methods Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry. Results Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027). Conclusion CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis. PMID:22355327

  2. PAP-a/CD81-LEL融合蛋白表达载体的构建%Construction of expression vector of PAP-a/CD81-LEL fusion protein

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    潘延凤; 贺永文; 刘薇; 郭劲松; 王华

    2005-01-01

    目的探讨将商陆抗病毒蛋白-a(PAP-a)与CD81的胞外大环(CD81-LEL)融合,并在大肠杆菌内表达.方法采用重叠延伸PCR方法,将PAP-a和CD81-LEL的基因拼接成PAP-a/CD81-LEL融合基因,并在两基因的连接处引入柔性肽段linker(GSGGSG)的核苷酸片断,然后将此融合基因克隆到原核表达载体PET-28a上,并在大肠杆菌BL21中进行表达.结果所获得的PAP-a/CD81-LEL融合基因经测序正确,并可以在大肠杆菌BL21中表达,经SDS-PAGE分析,重组蛋白的相对分子量为50 KD.结论PAP-a/CD81-LEL融合基因表达载体的成功构建与表达为进一步研究生物活性打下基础.

  3. Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients.

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    Paiva, B; Gutiérrez, N-C; Chen, X; Vídriales, M-B; Montalbán, M-Á; Rosiñol, L; Oriol, A; Martínez-López, J; Mateos, M-V; López-Corral, L; Díaz-Rodríguez, E; Pérez, J-J; Fernández-Redondo, E; de Arriba, F; Palomera, L; Bengoechea, E; Terol, M-J; de Paz, R; Martin, A; Hernández, J; Orfao, A; Lahuerta, J-J; Bladé, J; Pandiella, A; Miguel, J-F San

    2012-08-01

    The presence of CD19 in myelomatous plasma cells (MM-PCs) correlates with adverse prognosis in multiple myeloma (MM). Although CD19 expression is upregulated by CD81, this marker has been poorly investigated and its prognostic value in MM remains unknown. We have analyzed CD81 expression by multiparameter flow cytometry in MM-PCs from 230 MM patients at diagnosis included in the Grupo Español de Mieloma (GEM)05>65 years trial as well as 56 high-risk smoldering MM (SMM). CD81 expression was detected in 45% (103/230) MM patients, and the detection of CD81(+) MM-PC was an independent prognostic factor for progression-free (hazard ratio=1.9; P=0.003) and overall survival (hazard ratio=2.0; P=0.02); this adverse impact was validated in an additional series of 325 transplant-candidate MM patients included in the GEM05 <65 years trial. Moreover, CD81(+) SMM (n=34/56, 57%) patients had a shorter time to progression to MM (P=0.02). Overall, our results show that CD81 may have a relevant role in MM pathogenesis and represent a novel adverse prognostic marker in myeloma. PMID:22333880

  4. Up-regulation of CD81 (target of the antiproliferative antibody; TAPA) by reactive microglia and astrocytes after spinal cord injury int he rat

    NARCIS (Netherlands)

    Gispen, W.H.; Dijkstra, S.; Geisert Jr., E.E.; Bär, P.R; Joosten, E.A.J.

    2000-01-01

    We examined the expression of CD81 (also known as TAPA, or target of the antiproliferative antibody) after traumatic spinal cord injury in the rat. CD81, a member of the tetraspanin family of proteins, is thought to be involved in reactive gliosis. This is based on the antiproliferative and antiadhe

  5. Recombinant hepatitis C virus-envelope protein 2 interactions with low-density lipoprotein/CD81 receptors

    Directory of Open Access Journals (Sweden)

    Ana Carolina Urbaczek

    2015-06-01

    Full Text Available Hepatitis C virus (HCV envelope protein 2 (E2 is involved in viral binding to host cells. The aim of this work was to produce recombinant E2B and E2Y HCV proteins in Escherichia coli and Pichia pastoris, respectively, and to study their interactions with low-density lipoprotein receptor (LDLr and CD81 in human umbilical vein endothelial cells (HUVEC and the ECV304 bladder carcinoma cell line. To investigate the effects of human LDL and differences in protein structure (glycosylated or not on binding efficiency, the recombinant proteins were either associated or not associated with lipoproteins before being assayed. The immunoreactivity of the recombinant proteins was analysed using pooled serum samples that were either positive or negative for hepatitis C. The cells were immunophenotyped by LDLr and CD81 using flow cytometry. Binding and binding inhibition assays were performed in the presence of LDL, foetal bovine serum (FCS and specific antibodies. The results revealed that binding was reduced in the absence of FCS, but that the addition of human LDL rescued and increased binding capacity. In HUVEC cells, the use of antibodies to block LDLr led to a significant reduction in the binding of E2B and E2Y. CD81 antibodies did not affect E2B and E2Y binding. In ECV304 cells, blocking LDLr and CD81 produced similar effects, but they were not as marked as those that were observed in HUVEC cells. In conclusion, recombinant HCV E2 is dependent on LDL for its ability to bind to LDLr in HUVEC and ECV304 cells. These findings are relevant because E2 acts to anchor HCV to host cells; therefore, high blood levels of LDL could enhance viral infectivity in chronic hepatitis C patients.

  6. Transient gene expression mediated by integrase-defective retroviral vectors.

    Science.gov (United States)

    Yu, Seung Shin; Dan, Kazuyuki; Chono, Hideto; Chatani, Emi; Mineno, Junichi; Kato, Ikunoshin

    2008-04-18

    Nonintegrating retroviral vectors were produced from a Moloney murine leukemia virus (MoMLV)-based retroviral vector system by introducing a point mutation into the integrase (IN) gene of the packaging plasmid. The efficacy of IN-defective retroviral vectors was measured through the transient expression of ZsGreen or luciferase in human cell lines. The IN-defective retroviral vectors could transduce target cells efficiently, but their gene expression was transient and lower than that seen with the integrating vectors. IN-defective retroviral vector gene expression decreased to background levels in fewer than 10 days. Southern blot analysis of transduced K562 cells confirmed the loss of a detectable vector sequence by 15 days. The residual integration activity of the IN-defective vector was 1000- to 10,000-fold lower than that of the integrating vector. These results demonstrate that the IN-defective retroviral vectors can provide a useful tool for efficient transient gene expression targeting of primary hematopoietic stem cells and lymphoid cells.

  7. Biopanning and Identification of Peptides Capable to Inhibit the Interaction between hCD81 and HCV E2 Protein%能结合HCV E2蛋白的人CD81模拟肽的筛选与活性鉴定

    Institute of Scientific and Technical Information of China (English)

    廖小玲; 曹洁; 吴淑梅; 赵平; 高军; 戚中田

    2006-01-01

    目的 用CD81单克隆抗体筛选噬菌体随机展示十二肽库,以期得到可模拟人CD81功能位点、能抑制HCV E2与其受体一人CD81分子结合的小肽.方法 用CD81单抗从噬菌体随机展示十二肽库中筛选人CD81模拟肽,用ELISA鉴定阳性噬菌体克隆;以阳性噬菌体免疫BALB/c小鼠,分析小鼠免疫血清对阳性噬菌体与HCV E2结合的阻断作用;以HCV E2蛋白包被酶标板,检测阳性噬菌体对HCV E2与人CD81分子结合的抑制作用.结果 对十二肽库进行3轮筛选后,经ELISA和DNA测序,鉴定出3个(C4,C13和C16)阳性克隆,与人CD81无同源序列.阳性噬菌体克隆C16免疫小鼠血清能阻断该克隆与HCV E2的结合.C16克隆能以剂量依赖的方式竞争性抑制HCV E2蛋白与人CD81的结合.结论 用人CD81单抗从噬菌体随机展示肽库中筛选出的阳性噬菌体克隆所编码的小肽在功能上能模拟人CD81与HCV E2的结合活性,能竞争性抑制HCV E2与人CD81分子的结合,在抗HCV药物及疫苗研究中具有潜在应用价值.

  8. Approaches to diagnose DNA mismatch repair gene defects in cancer.

    Science.gov (United States)

    Peña-Diaz, Javier; Rasmussen, Lene Juel

    2016-02-01

    The DNA repair pathway mismatch repair (MMR) is responsible for the recognition and correction of DNA biosynthetic errors caused by inaccurate nucleotide incorporation during replication. Faulty MMR leads to failure to address the mispairs or insertion deletion loops (IDLs) left behind by the replicative polymerases and results in increased mutation load at the genome. The realization that defective MMR leads to a hypermutation phenotype and increased risk of tumorigenesis highlights the relevance of this pathway for human disease. The association of MMR defects with increased risk of cancer development was first observed in colorectal cancer patients that carried inactivating germline mutations in MMR genes and the disease was named as hereditary non-polyposis colorectal cancer (HNPCC). Currently, a growing list of cancers is found to be MMR defective and HNPCC has been renamed Lynch syndrome (LS) partly to include the associated risk of developing extra-colonic cancers. In addition, a number of non-hereditary, mostly epigenetic, alterations of MMR genes have been described in sporadic tumors. Besides conferring a strong cancer predisposition, genetic or epigenetic inactivation of MMR genes also renders cells resistant to some chemotherapeutic agents. Therefore, diagnosis of MMR deficiency has important implications for the management of the patients, the surveillance of their relatives in the case of LS and for the choice of treatment. Some of the alterations found in MMR genes have already been well defined and their pathogenicity assessed. Despite this substantial wealth of knowledge, the effects of a large number of alterations remain uncharacterized (variants of uncertain significance, VUSs). The advent of personalized genomics is likely to increase the list of VUSs found in MMR genes and anticipates the need of diagnostic tools for rapid assessment of their pathogenicity. This review describes current tools and future strategies for addressing the relevance

  9. A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits Hepatitis C virus cell-cell transmission.

    Directory of Open Access Journals (Sweden)

    Isabel Fofana

    Full Text Available BACKGROUND AND AIMS: Hepatitis C virus (HCV infection is a challenge to prevent and treat because of the rapid development of drug resistance and escape. Viral entry is required for initiation, spread, and maintenance of infection, making it an attractive target for antiviral strategies. METHODS: Using genetic immunization, we produced four monoclonal antibodies (mAbs against the HCV host entry factor CD81. The effects of antibodies on inhibition of HCV infection and dissemination were analyzed in HCV permissive human liver cell lines. RESULTS: The anti-CD81 mAbs efficiently inhibited infection by HCV of different genotypes as well as a HCV escape variant selected during liver transplantation and re-infecting the liver graft. Kinetic studies indicated that anti-CD81 mAbs target a post-binding step during HCV entry. In addition to inhibiting cell-free HCV infection, one antibody was also able to block neutralizing antibody-resistant HCV cell-cell transmission and viral dissemination without displaying any detectable toxicity. CONCLUSION: A novel anti-CD81 mAb generated by genetic immunization efficiently blocks HCV spread and dissemination. This antibody will be useful to further unravel the role of virus-host interactions during HCV entry and cell-cell transmission. Furthermore, this antibody may be of interest for the development of antivirals for prevention and treatment of HCV infection.

  10. Hypertrophic cardiomyopathy: from gene defect to clinical disease

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Major advances have been made over the last decade in our understanding of the molecular basis ofseveral cardiac conditions. Hypertrophic cardiomyopathy (HCM) was the first cardiac disorder in whicha genetic basis was identified and as such, has acted as a paradigm for the study of an inherited cardiacdisorder. HCM can result in clinical symptoms ranging from no symptoms to severe heart failure andpremature sudden death. HCM is the commonest cause of sudden death in those aged less than 35 years,including competitive athletes. At least ten genes have now been identified, defects in which cause HCM.All of these genes encode proteins which comprise the basic contractile unit of the heart, i.e. the sarcomere.While much is now known about which genes cause disease and the various clinical presentations, very littleis known about how these gene defects cause disease, and what factors modify the expression of the mutantgenes. Studies in both cell culture and animal models of HCM are now beginning to shed light on thesignalling pathways involved in HCM, and the role of both environmental and genetic modifying factors.Understanding these mechanisms will ultimately improve our knowledge of the basic biology of heart musclefunction, and will therefore provide new avenues for treating cardiovascular disease in man.

  11. Maternal-Fetal Metabolic Gene-Gene Interactions and Risk of Neural Tube Defects

    OpenAIRE

    Lupo, Philip J.; Mitchell, Laura E; Canfield, Mark A.; Shaw, Gary M.; Olshan, Andrew F.; Finnell, Richard H.; Zhu, Huiping

    2013-01-01

    Single-gene analyses indicate that maternal genes associated with metabolic conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs). However, to our knowledge, there have been no assessments of maternal-fetal metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were obtained from 737 NTD c...

  12. Marfan syndrome gene search intensifies following identification of basic defect

    Energy Technology Data Exchange (ETDEWEB)

    Randall, T.

    1990-10-03

    Somewhere, quite possible along chromosomes 8 and/or 15, the gene(s) for Marfan syndrome will be found. The search is intensifying following a report that faulty scaffolding in the body's connective tissue appears to be the long sought after defect behind the syndrome, and inherited disorder that has caused the premature death of young, healthy-looking individuals. Finding that something in the living masonry of the human body has proven to be a 30-year inquisition of nearly two dozen molecules that has engaged investigators worldwide. Historically, researchers have searched for a structural flaw in one of the collagen molecules to explain the cause of Marfan Syndrome. Using monoclonal antibodies, researchers have implicated microfibrils, the extracellular filaments that provide a matrix for the deposit of elastin during embryonic development.

  13. Blue ghosts: a new method for isolating amber mutants defective in essential genes of Escherichia coli

    DEFF Research Database (Denmark)

    Brown, S; Brickman, E R; Beckwith, J

    1981-01-01

    We describe a technique which permits an easy screening for amber mutants defective in essential genes of Escherichia coli. Using this approach, we have isolated three amber mutants defective in the rho gene. An extension of the technique allows the detection of ochre mutants and transposon inser...

  14. Maternal-fetal metabolic gene-gene interactions and risk of neural tube defects.

    Science.gov (United States)

    Lupo, Philip J; Mitchell, Laura E; Canfield, Mark A; Shaw, Gary M; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

    2014-01-01

    Single-gene analyses indicate that maternal genes associated with metabolic conditions (e.g., obesity) may influence the risk of neural tube defects (NTDs). However, to our knowledge, there have been no assessments of maternal-fetal metabolic gene-gene interactions and NTDs. We investigated 23 single nucleotide polymorphisms among 7 maternal metabolic genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, and TCF7L2) and 2 fetal metabolic genes (SLC2A2 and UCP2). Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study for birth years 1999-2007. We used a 2-step approach to evaluate maternal-fetal gene-gene interactions. First, a case-only approach was applied to screen all potential maternal and fetal interactions (n = 76), as this design provides greater power in the assessment of gene-gene interactions compared to other approaches. Specifically, ordinal logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for each maternal-fetal gene-gene interaction, assuming a log-additive model of inheritance. Due to the number of comparisons, we calculated a corrected p-value (q-value) using the false discovery rate. Second, we confirmed all statistically significant interactions (q < 0.05) using a log-linear approach among case-parent triads. In step 1, there were 5 maternal-fetal gene-gene interactions with q < 0.05. The "top hit" was an interaction between maternal ENPP1 rs1044498 and fetal SLC2A2 rs6785233 (interaction OR = 3.65, 95% CI: 2.32-5.74, p = 2.09×10(-8), q=0.001), which was confirmed in step 2 (p = 0.00004). Our findings suggest that maternal metabolic genes associated with hyperglycemia and insulin resistance and fetal metabolic genes involved in glucose homeostasis may interact to increase the risk of NTDs. PMID:24332798

  15. Filaggrin gene defects and the risk of developing allergic disorders.

    Science.gov (United States)

    Osawa, Rinko; Akiyama, Masashi; Shimizu, Hiroshi

    2011-03-01

    Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and have been shown to be major predisposing factors for atopic dermatitis (AD). Approximately 40 loss-of-function FLG mutations have been identified in patients with ichthyosis vulgaris (IV) and/or atopic dermatitis (AD) in Europe and Asia. Major differences exist in the spectra of FLG mutations observed between different ancestral groups. Notably, prevalent FLG mutations are distinct between European and Asian populations. Many cohort studies on FLG mutations in AD have revealed that approximately 25-50% of AD patients harbour filaggrin mutations as a predisposing factor. In addition, FLG mutations are significantly associated with AD-associated asthma. The risk for developing allergic rhinitis is also significantly higher with a FLG mutation, both with and without accompanying AD. Recent studies have hypothesized that skin barrier defects caused by FLG mutations allows allergens to penetrate the epidermis and to interact with antigen-presenting cells, leading to the development of atopic disorders including asthma. The restoration of skin barrier function seems a feasible and promising strategy for prophylactic treatment of AD patients with FLG mutations.

  16. Diabetes and Obesity-Related Genes and the Risk of Neural Tube Defects in the National Birth Defects Prevention Study

    OpenAIRE

    Lupo, Philip J.; Canfield, Mark A.; Chapa, Claudia; Lu, Wei; Agopian, A.J.; Mitchell, Laura E; Shaw, Gary M.; Waller, D. Kim; Olshan, Andrew F.; Finnell, Richard H.; Zhu, Huiping

    2012-01-01

    Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999–2007. Log-linear models were used to evaluate maternal and...

  17. Study on the relationship between the RAR-β gene expressive defection and its methylation

    Institute of Scientific and Technical Information of China (English)

    高艳萍; 李敏; 张颖颖; 王翰; 贺小红; 王泽华

    2007-01-01

    Objective To observe the expression of RAR-β gene in SiHa, HeLa,C33A and CasKi cell lines of cervical carcinoma and to investigate the role of methylated RAR-β in its expressive defection. Methods Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression of RAR-β gene. Immunohistochemistry and Western Blot were used to analyze the protein expression of RAR-β gene in four cervical cancer cell lines as well as the influence of 5-Aza-cdR on gene expressive defection. Meth...

  18. Osteopathia Striata With Cranial Sclerosis Owing to WTX Gene Defect

    NARCIS (Netherlands)

    Perdu, Bram; de Freitas, Fenna; Frints, Suzanne G. M.; Schouten, Meyke; Schrander-Stumpel, Connie; Barbosa, Mafalda; Pinto-Basto, Jorge; Reis-Lima, Margarida; de Vernejoul, Marie-Christine; Becker, Kristin; Freckmann, Marie-Louise; Keymolen, Kathlijn; Haan, Eric; Savarirayan, Ravi; Koenig, Rainer; Zabel, Bernhard; Vanhoenacker, Filip M.; Van Hul, Wim

    2010-01-01

    Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant condition marked by linear striations mainly affecting the metaphyseal region of the long bones and pelvis in combination with cranial sclerosis. Recently, the disease-causing gene was identified as the WTX gene (FAM123B), an

  19. Retinoic acid induction of genes associated with neural tube developmental defects

    Institute of Scientific and Technical Information of China (English)

    Xinjun Li; Zhong Yang; Yi Zeng; Hong Xu; Hongli Li; Yangyun Han; Xiaodong Long; Chao You

    2010-01-01

    To date, little information has been available regarding genes involved in the regulation of embryonic cell development, which participate in retinoic acid-induced neural tube defects in mice.Previous studies have revealed seven differentially expressed genes involved in neural tube developmental defects. However, gene expression and regulation is a complex process. Therefore,gene expression differences between normal and defective neural tubes at 9.5 and 10.5 days were compared. A total of eight differentially expressed genes exhibited coincident alterations at embryonic 9.5 and 10.5 days. In mice with retinoic acid-induced neural tube defects, NeK7, IGFBP5,ZW10, Csf3r, PSMC6, Cdk5, and Rb1 expressions were downregulated, but Apoa-4 expression was upregulated. These results were confirmed by Northern blot hybridization. Results suggested that NeK7, IGFBP5, ZW10, Csf3r, PSMC6, Cdk5, Rb1, and Apoa-4 are important regulatory factors involved in neural tube defects.

  20. A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation

    OpenAIRE

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-01-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with ...

  1. Approaches to diagnose DNA mismatch repair gene defects in cancer

    DEFF Research Database (Denmark)

    Peña-Diaz, Javier; Rasmussen, Lene Juel

    2016-01-01

    already been well defined and their pathogenicity assessed. Despite this substantial wealth of knowledge, the effects of a large number of alterations remain uncharacterized (variants of uncertain significance, VUSs). The advent of personalized genomics is likely to increase the list of VUSs found in MMR...... genes and anticipates the need of diagnostic tools for rapid assessment of their pathogenicity. This review describes current tools and future strategies for addressing the relevance of MMR gene alterations in human disease....... genes also renders cells resistant to some chemotherapeutic agents. Therefore, diagnosis of MMR deficiency has important implications for the management of the patients, the surveillance of their relatives in the case of LS and for the choice of treatment. Some of the alterations found in MMR genes have...

  2. Diabetes and "defective" genes in the twentieth-century United States.

    Science.gov (United States)

    Tuchman, Arleen Marcia

    2015-01-01

    In the decades following the discovery of insulin, eugenicists grew concerned that more diabetics would survive into their reproductive years and contribute "defective" genes to the gene pool. Insulin thus came to be seen as both a blessing for the individual and a problem for the future of humankind. Nevertheless, diabetics in the United States were neither prevented nor discouraged from reproducing. I argue that this stemmed from the widespread belief that diabetes was a disease primarily of middle-class whites, who possessed positive traits that outweighed their particular genetic defect. Historians of eugenics have demonstrated convincingly that race and class stereotypes made some populations more vulnerable to coercive eugenic practices. The case of diabetes demonstrates that race and class stereotypes could also confer protection. In the end, possession of a defective gene mattered less than the perception of one's contribution to society. PMID:23982987

  3. Candidate genes of hypertension with defective environmental expression

    Institute of Scientific and Technical Information of China (English)

    SUNYULIN; JOHANNETREMBLAY; 等

    1995-01-01

    Previous studies in our laboratory have demonstrated that the thermosensitivity locus cosegregates with blood pressure and that the elevated expression and restriction fragment length polymorphism of HSP70 gene are associated with hypertension.Cell protection against environmental stressors such as heat and chemicals is often accompanied by up-regulated expression of a wide spectrum of heat shock genes(HSP).To further investigate the interrelation between HSP expression and blood pressure regulation,we employed an effective method of cloning 2 potential hypertension-related HSPs.Synthetic oligonucleotides corresponding either to a highly-conserved region of the known HSP family or a repetitive sequence in the proteinencoding gene were used as target primers for polymerase chain reaction(PCR).cDNA prepared from heat-stressed and non-stressed vascular smooth muscle cells(VSMC)of Brown Norway rats(BN.1x)and spontaneously hypertensive rats(SHRp) respectively served as template in the reaction.The PCR products were subsequently analyzed in a single-stranded conformational polymorphism(SSCP) electrophoresing system.Differential gene expression in BN.1x and SHRp was seen on autoradiographs of SSCP gel by comparing the migration patterns of PCR-amplified DNA fragments.Using this technique,we also found that HSP27 and a new member of the large HSP gene family were differentially expressed in BN.1x and SHRp VSMC.

  4. Association of TBX5 gene polymorphism with ventricular septal defect in the Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    LIU Cai-xia; SHEN A-dong; LI Xiao-feng; JIAO Wei-wei; BAI Song; YUAN Feng; GUAN Xiao-lei; ZHANG Xin-gen; ZHANG Gui-rong; LI Zhong-zhi

    2009-01-01

    Background Congenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population. Methods One hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to 15erform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method. Results The TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P=0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P=0.05, multiple loci regression analyses based on reconstructed haplotype blocks). Conclusions TBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Hart Chinese. This finding has set a direction for further genetic and functional studies.

  5. Polymorphisms of the maternal Slug gene in fetal neural tube defects in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    Li Guo; Hong Zhao; Yuheng Pei; Quanren He; Wan-I Li; Ting Zhang; Xiaoying Zheng; Ran Zhou; Jun Xie

    2010-01-01

    Several studies have demonstrated that Slug,which encodes a zinc finger of the Snail family of transcription factors,is a potential risk factor for neural tube defects.Neural tube defects tend to occur with a high rate in Shanxi province,China.The present case-control study investigated genotypic distributions and allele frequencies of Slug C1548A polymorphisms in DNA samples from59 women with a history of neural tube defect pregnancies and 73 controls during the same period from Shanxi Province,China.Results demonstrated that women with a history of neural tube defect pregnancies had significantly greater genotypic distributions of Slug AA genotypes and A allele frequencies compared with controls,and A allele Slug C1548A was a risk factor for neural tube defects(odds ratio = 3.444;95% confidence interval;2.021-5.868,P < 0.05).Three-dimensional structure prediction revealed that Slug C1548A resulted in transition of aspartic acid into glutamate at position 119.This indicated that these mutations could lead to damaged protein structure and function.These findings suggest that Slug C1548A gene polymorphism is closely related to neural tube defects in a population of Han Chinese origin from Shanxi Province,China

  6. Diabetes and Obesity-Related Genes and the Risk of Neural Tube Defects in the National Birth Defects Prevention Study

    Science.gov (United States)

    Lupo, Philip J.; Canfield, Mark A.; Chapa, Claudia; Lu, Wei; Agopian, A. J.; Mitchell, Laura E.; Shaw, Gary M.; Waller, D. Kim; Olshan, Andrew F.; Finnell, Richard H.; Zhu, Huiping

    2012-01-01

    Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999–2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy. PMID:23132673

  7. Diabetes and obesity-related genes and the risk of neural tube defects in the national birth defects prevention study.

    Science.gov (United States)

    Lupo, Philip J; Canfield, Mark A; Chapa, Claudia; Lu, Wei; Agopian, A J; Mitchell, Laura E; Shaw, Gary M; Waller, D Kim; Olshan, Andrew F; Finnell, Richard H; Zhu, Huiping

    2012-12-15

    Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy. PMID:23132673

  8. Folate-related gene variants in Irish families affected by neural tube defects

    Directory of Open Access Journals (Sweden)

    Ridgely eFisk Green

    2013-11-01

    Full Text Available Periconceptional folic acid use can often prevent neural tube defects (NTDs. Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (risk genotypes and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p=0.017. We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential

  9. Structural gene for beta-nerve growth factor not defective in familial dysautonomia.

    OpenAIRE

    Breakefield, X O; Orloff, G; Castiglione, C; Coussens, L.; Axelrod, F. B.; Ullrich, A

    1984-01-01

    The developmental loss of neurons in sympathetic, sensory, and some parasympathetic ganglia in familial dysautonomia suggests an inherited defect in the action of beta-nerve growth factor (beta-NGF). The role of this growth factor in dysautonomia has been difficult to resolve as there is no known source of authentic human beta-NGF. The availability of a cloned DNA probe for the human beta-NGF gene has allowed identification of some copies of the gene (alleles) in six affected families. Allele...

  10. Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects

    Institute of Scientific and Technical Information of China (English)

    Ji-Ping Shan; Xiao-Li Wang; Yuan-Gang Qiao; Hong-Xin Wan Yan; Wen-Hui Huang; Shu-Chao Pang; Bo Yan

    2014-01-01

    Background: Congenital heart disease (CHD) is the most common human birth defect. Genetic causes for CHD remain largely unknown. GATA transcription factor 5 (GATA 5) is an essential regulator for the heart development. Mutations in the GATA5 gene have been reported in patients with a variety of CHD. Since misregulation of gene expression have been associated with human diseases, we speculated that changed levels of cardiac transcription factors, GATA5, may mediate the development of CHD. Methods: In this study, GATA5 gene promoter was genetically and functionally analyzed in large cohorts of patients with ventricular septal defect (VSD) (n=343) and ethnic-matched healthy controls (n=348). Results: Two novel and heterozygous DNA sequence variants (DSVs), g.61051165A>G and g.61051463delC, were identified in three VSD patients, but not in the controls. In cultured cardiomyocytes, GATA5 gene promoter activities were significantly decreased by DSV g.61051165A>G and increased by DSV g.61051463delC. Moreover, fathers of the VSD patients carrying the same DSVs had reduced diastolic function of left ventricles. Three SNPs, g.61051279C>T (rs77067995), g.61051327A>C (rs145936691) and g.61051373G>A (rs80197101), and one novel heterozygous DSV, g.61051227C>T, were found in both VSD patients and controls with similar frequencies. Conclusion: Our data suggested that the DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor.

  11. A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.

    Science.gov (United States)

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-05-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with nonsyndromic ARMR in four sibships. Genome-wide SNP typing enabled us to map the relevant genetic defect to a 4.6 Mbp interval on chromosome 8. Haplotype analyses and copy-number studies led to the identification of a homozygous deletion partly removing TUSC3 (N33) in all patients. All obligate carriers of this family were heterozygous, but none of 192 unrelated healthy individuals from the same population carried this deletion. We excluded other disease-causing mutations in the coding regions of all genes within the linkage interval by sequencing; moreover, we verified the complete absence of a functional TUSC3 transcript in all patients through RT-PCR. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltransferase complex that catalyzes a pivotal step in the protein N-glycosylation process. Our data suggest that in contrast to other genetic defects of glycosylation, inactivation of TUSC3 causes nonsyndromic MR, a conclusion that is supported by a separate report in this issue of AJHG. TUSC3 is only the fifth gene implicated in NS-ARMR and the first for which mutations have been reported in more than one family. PMID:18452889

  12. Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

    Directory of Open Access Journals (Sweden)

    Wakako Jo

    2010-01-01

    Full Text Available Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD. Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although 123I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

  13. Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V Leiden mothers

    Science.gov (United States)

    Sood, Rashmi; Zogg, Mark; Westrick, Randal J.; Guo, Yi-he; Kerschen, Edward J.; Girardi, Guillermina; Salmon, Jane E.; Coughlin, Shaun R.; Weiler, Hartmut

    2007-01-01

    We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which fetal loss is triggered when the maternal prothrombotic state coincides with fetal gene defects that reduce activation of the protein C anticoagulant pathway within the placenta. Fetal loss is caused by disruption of placental morphogenesis at the stage of labyrinth layer formation and occurs in the absence of overt placental thrombosis, infarction, or perfusion defects. Platelet depletion or elimination of protease-activated receptor 4 (Par4) from the mother allows normal placentation and prevents fetal loss. These findings establish a cause–effect relationship for the observed epidemiologic association between maternal FvL status and fetal loss and identify fetal gene defects as risk modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is mediated by Par4-dependent activation of maternal platelets at the fetomaternal interface and likely involves a pathogenic pathway independent of occlusive thrombosis. Our results further demonstrate that the interaction of two given thrombosis risk factors produces markedly disparate consequences on disease manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed in which this interaction occurs. PMID:17438064

  14. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    BACKGROUND: Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown.OBJECTIVE: To compare the differences in gene expression between normal embryos and those with neural tube defects.DESIGN, TIME AND SETTING: A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007.MATERIALS: Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group (n = 30) and a normal control group (n =30). The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA.METHODS: Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similady administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic (E) clay 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray.MAIN OUTCOME MEASURES: Morphological changes and differential gene expression between the normal control group and the retinoic acid group.RESULTS: Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of

  15. Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

    Science.gov (United States)

    Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

    2015-06-01

    Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity.

  16. Mutations in the Motile Cilia Gene DNAAF1 Are Associated with Neural Tube Defects in Humans

    Directory of Open Access Journals (Sweden)

    Chunyue Miao

    2016-10-01

    Full Text Available Neural tube defects (NTDs are severe malformations of the central nervous system caused by complex genetic and environmental factors. Among genes involved in NTD, cilia-related genes have been well defined and found to be essential for the completion of neural tube closure (NTC. We have carried out next-generation sequencing on target genes in 373 NTDs and 222 healthy controls, and discovered eight disease-specific rare mutations in cilia-related gene DNAAF1. DNAAF1 plays a central role in cytoplasmic preassembly of distinct dynein-arm complexes, and is expressed in some key tissues involved in neural system development, such as neural tube, floor plate, embryonic node, and brain ependyma epithelial cells in zebrafish and mouse. Therefore, we evaluated the expression and functions of mutations in DNAAF1 in transfected cells to analyze the potential correlation of these mutants to NTDs in humans. One rare frameshift mutation (p.Gln341Argfs*10 resulted in significantly diminished DNAAF1 protein expression, compared to the wild type. Another mutation, p.Lys231Gln, disrupted cytoplasmic preassembly of the dynein-arm complexes in cellular assay. Furthermore, results from NanoString assay on mRNA from NTD samples indicated that DNAAF1 mutants altered the expression level of NTC-related genes. Altogether, these findings suggest that the rare mutations in DNAAF1 may contribute to the susceptibility for NTDs in humans.

  17. Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects

    Directory of Open Access Journals (Sweden)

    Ali Etemad

    2013-01-01

    Full Text Available Ventricular septal defect (VSD is one of the most common types of congenital heart defects (CHD. There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR and methylenetetrahydrofolate reductase (MTHFR are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05 in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects.

  18. Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects.

    Science.gov (United States)

    Pishva, Seyyed Reza; Vasudevan, Ramachandran; Etemad, Ali; Heidari, Farzad; Komara, Makanko; Ismail, Patimah; Othman, Fauziah; Karimi, Abdollah; Sabri, Mohammad Reza

    2013-01-01

    Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects. PMID:23358257

  19. Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene

    NARCIS (Netherlands)

    M. Gerards; B.J.C. van den Bosch; K. Danhauser; V. Serre; M. van Weeghel; R.J.A. Wanders; G.A.F. Nicolaes; W. Sluiter; K. Schoonderwoerd; H.R. Scholte; H. Prokisch; A. Rötig; I.F.M. de Coo; H.J.M. Smeets

    2011-01-01

    Mitochondrial complex I deficiency is the most common oxidative phosphorylation defect. Mutations have been detected in mitochondrial and nuclear genes, but the genetics of many patients remain unresolved and new genes are probably involved. In a consanguineous family, patients presented easy fatiga

  20. A study on the possible involvement of the PAX3 gene in human neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Hol, F.A.; Hamel, B.C.J.; Geurds, M.P.A. [University Hospital Nijmegen (Netherlands)] [and others

    1994-09-01

    Neural tube defects (NTD) are congenital malformations of the central nervous system which are generally attributed to a combination of environmental and genetic factors. Recently, the molecular defect responsible for the phenotype of the Splotch mouse, a monogenic model system for NTD, was determined. A mutation disrupts the homeodomain of the gene for Pax3. In humans, mutations in the cognate gene for PAX3 can cause Waardenburg syndrome (WS), which is associated with NTD. Based on these findings, PAX3 can be regarded as a candidate gene for human NTD. To test this hypothesis we have screened the DNA of 39 familial and 70 sporadic NTD patients for mutations in the coding exons and flanking intron sequences of the PAX3 gene. SSC analysis revealed abnormal bands in exon 2, exon 5, exon 6 and exon 7 in different patients. A missense mutation was identified in exon 6 downstream from the homeodomain in several patients resulting in an amino acid substitution (Thr315Lys) in the protein. However, the same substitution was detected in unaffected controls suggesting no biological significance. Above shifts most likely represent polymorphisms that are irrelevant for NTD. A conspicuous SSC-band shift was observed in exon 5 of one familial patient with spina bifida. Sequencing revealed that the patient was heterozygous for a 5 bp deletion upstream of the homeodomain. The deletion causes a frameshift, which leads to premature termination of translation. Mild characteristics of WS were detected in several members of the family including the index patient. DNA analysis showed co-segregation of the mutation with these symptoms. Although PAX3 mutations can increase the penetrance of NTD in families with WS, our results show that their presence is not sufficient to cause NTD.

  1. Identification of novel candidate gene loci and increased sex chromosome aneuploidy among infants with conotruncal heart defects.

    Science.gov (United States)

    Osoegawa, Kazutoyo; Iovannisci, David M; Lin, Bin; Parodi, Christina; Schultz, Kathleen; Shaw, Gary M; Lammer, Edward J

    2014-02-01

    Congenital heart defects (CHDs) are common malformations, affecting four to eight per 1,000 total births. Conotruncal defects are an important pathogenetic subset of CHDs, comprising nearly 20% of the total. Although both environmental and genetic factors are known to contribute to the occurrence of conotruncal defects, the causes remain unknown for most. To identify novel candidate genes/loci, we used array comparative genomic hybridization to detect chromosomal microdeletions/duplications. From a population base of 974,579 total births born during 1999-2004, we screened 389 California infants born with tetralogy of Fallot or d-transposition of the great arteries. We found that 1.7% (5/288) of males with a conotruncal defect had sex chromosome aneuploidy, a sevenfold increased frequency (relative risk = 7.0; 95% confidence interval 2.9-16.9). We identified eight chromosomal microdeletions/duplications for conotruncal defects. From these duplications and deletions, we found five high priority candidate genes (GATA4, CRKL, BMPR1A, SNAI2, and ZFHX4). This is the initial report that sex chromosome aneuploidy is associated with conotruncal defects among boys. These chromosomal microduplications/deletions provide evidence that GATA4, SNAI2, and CRKL are highly dosage sensitive genes involved in outflow tract development. Genome wide screening for copy number variation can be productive for identifying novel genes/loci contributing to non-syndromic common malformations.

  2. Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function.

    Science.gov (United States)

    Clementi, Rita; Chiocchetti, Annalisa; Cappellano, Giuseppe; Cerutti, Elisa; Ferretti, Massimo; Orilieri, Elisabetta; Dianzani, Irma; Ferrarini, Marina; Bregni, Marco; Danesino, Cesare; Bozzi, Valeria; Putti, Maria Caterina; Cerutti, Franco; Cometa, Angela; Locatelli, Franco; Maccario, Rita; Ramenghi, Ugo; Dianzani, Umberto

    2006-11-01

    Mutations decreasing function of the Fas death receptor cause the autoimmune lymphoproliferative syndrome (ALPS) with autoimmune manifestations, spleen/lymph node enlargement, and expansion of CD4/CD8-negative T cells. Dianzani Autoimmune Lymphoproliferative Disease (DALD) is a variant lacking this expansion. Perforin is involved in cell-mediated cytotoxicity and its biallelic mutations cause familial hemophagocytic lymphohistiocytosis (HLH). We previously described an ALPS patient carrying heterozygous mutations of the Fas and perforin genes and suggested that they concurred in ALPS. This work extends the analysis to 14 ALPS, 28 DALD, and 816 controls, and detects an N252S amino acid substitution in 2 ALPS, and an A91V amino acid substitution in 6 DALD. N252S conferred an OR = 62.7 (P = .0016) for ALPS and A91V conferred an OR = 3 (P = .016) for DALD. Copresence of A91V and variations of the osteopontin gene previously associated with DALD conferred an OR = 17 (P = .0007) for DALD. In one N252S patient, NK activity was strikingly defective in early childhood, but became normal in late childhood. A91V patients displayed lower NK activity than controls. These data suggest that perforin variations are a susceptibility factor for ALPS/DALD development in subjects with defective Fas function and may influence disease expression. PMID:16720836

  3. Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer

    Energy Technology Data Exchange (ETDEWEB)

    Goyette, M.C.; Fasching, C.L.; Stanbridge, E.J. (Univ. of California, Irvine (United States)); Cho, K.; Levy, D.B.; Kinzler, K.W.; Vogelstein, B. (John Hopkins Univ. School of Medicine and Hospital, Baltimore, MD (United States)); Paraskeva, C. (Univ. of Bristol, University Walk, Bristol (United Kingdom))

    1992-03-01

    Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, the authors have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 5 express the APC gene present on that chromosome as well as the endogenous mutant transcript. Expression of the putative tumor suppressor gene, DCC, was seen in the clones containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.

  4. A cancer derived mutation in the Retinoblastoma gene with a distinct defect for LXCXE dependent interactions

    Directory of Open Access Journals (Sweden)

    Demone Jordan

    2010-03-01

    Full Text Available Abstract Background The interaction between viral oncoproteins such as Simian virus 40 TAg, adenovirus E1A, and human papilloma virus E7, and the retinoblastoma protein (pRB occurs through a well characterized peptide sequence, LXCXE, on the viral protein and a well conserved groove in the pocket domain of pRB. Cellular proteins, such as histone deacetylases, also use this mechanism to interact with the retinoblastoma protein to repress transcription at cell cycle regulated genes. For these reasons this region of the pRB pocket domain is thought to play a critical role in growth suppression. Results In this study, we identify and characterize a tumor derived allele of the retinoblastoma gene (RB1 that possesses a discrete defect in its ability to interact with LXCXE motif containing proteins that compromises proliferative control. To assess the frequency of similar mutations in the RB1 gene in human cancer, we screened blood and tumor samples for similar alleles. We screened almost 700 samples and did not detect additional mutations, indicating that this class of mutation is rare. Conclusions Our work provides proof of principal that alleles encoding distinct, partial loss of function mutations in the retinoblastoma gene that specifically lose LXCXE dependent interactions, are found in human cancer.

  5. Identification of Residues Responsible for the Defective Virulence Gene Regulator Mga Produced by a Natural Mutant of Streptococcus pyogenes

    OpenAIRE

    Vahling, Cheryl M.; McIver, Kevin S.

    2005-01-01

    Mga is a transcriptional regulator in the pathogen Streptococcus pyogenes that positively activates several important virulence genes involved in colonization and immune evasion in the human host. A naturally occurring mutant of Mga that is defective in its ability to activate transcription has been identified in the serotype M50 strain B514-Sm. Sequence alignment of the defective M50 Mga with the fully functional Mga from serotypes M4 and M49 revealed only three amino acid changes that might...

  6. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    LENUS (Irish Health Repository)

    Pangilinan, Faith

    2012-08-02

    AbstractBackgroundNeural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1 rs2236225 (R653Q)) have been found to increase NTD risk. We hypothesized that variants in additional folate\\/B12 pathway genes contribute to NTD risk.MethodsA tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate\\/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents), including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects.ResultsNearly 70 SNPs in 30 genes were found to be associated with NTDs at the p < 0.01 level. The ten strongest association signals (p-value range: 0.0003–0.0023) were found in nine genes (MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury)) and included the known NTD risk factor MTHFD1 R653Q (rs2236225). The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele). Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing.ConclusionsTo our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the

  7. Efficient Gene Transfer Mediated by HIV-1-based Defective Lentivector and Inhibition of HIV-1 Replication

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Lentiviral vectors have drawn considerable attention recently and show great promise to become important delivery vehicles for future gene transfer manipulation. In the present study we have optimized a protocol for preparation of human immunodeficiency virus type-1 (HIV-1)-based defective lentiviral vectors (DLV) and characterized these vectors in terms of their transduction of different cells. Transient co-transfection of 293T packaging cells with DNA plasmids encoding lentiviral vector constituents resulted in production of high-titer DLV (0.5-1.2 × 107IU/mL), which can be further concentrated over 100-fold through a single step ultracentrifugation. These vectors were capable of transducing a variety of cells from both primate and non-primate sources and high transduction efficiency was achieved using concentrated vectors. Assessment of potential generation of RCV revealed no detection of infection by infectious particles in DLV-transduced CEM, SupT-1 and MT-2 cells. Long-term culture of transduced cells showed a stable expression of transgenes without apparent alteration in cellular morphology and growth kinetics. Vector mobilization to untransduced cells mediated by wild-type HIV-1 infection was confirmed in this test. Challenge of transduced human T-lymphocytes with wild-type HIV-1 showed these cells are totally resistant to the viral infection. Considering the effective gene transfer and stable gene expression, safety and anti-HIV activity, these DLV vectors warrant further exploration for their potential use as a gene transfer vehicle in the development of gene therapy protocols.

  8. Disorders of phospholipid metabolism: an emerging class of mitochondrial disease due to defects in nuclear genes

    Directory of Open Access Journals (Sweden)

    Ya-Wen eLu

    2015-02-01

    Full Text Available The human nuclear and mitochondrial genomes co-exist within each cell. While the mitochondrial genome encodes for a limited number of proteins, transfer RNAs, and ribosomal RNAs, the vast majority of mitochondrial proteins are encoded in the nuclear genome. Of the multitude of mitochondrial disorders known to date, only a fifth are maternally inherited. The recent characterization of the mitochondrial proteome therefore serves as an important step towards delineating the nosology of a large spectrum of phenotypically heterogeneous diseases. Following the identification of the first nuclear gene defect to underlie a mitochondrial disorder, a plenitude of genetic variants that provoke mitochondrial pathophysiology have been molecularly elucidated and classified into six categories that impact: 1 oxidative phosphorylation (subunits and assembly factors; 2 mitochondrial DNA maintenance and expression; 3 mitochondrial protein import and assembly; 4 mitochondrial quality control (chaperones and proteases; 5 iron-sulfur cluster homeostasis; and 6 mitochondrial dynamics (fission and fusion. Here, we propose that an additional class of genetic variant be included in the classification schema to acknowledge the role of genetic defects in phospholipid biosynthesis, remodeling, and metabolism in mitochondrial pathophysiology. This seventh class includes a small but notable group of nuclear-encoded proteins whose dysfunction impacts normal mitochondrial phospholipid metabolism. The resulting human disorders present with a diverse array of pathologic consequences that reflect the variety of functions that phospholipids have in mitochondria and highlight the important role of proper membrane homeostasis in mitochondrial biology.

  9. Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects

    Directory of Open Access Journals (Sweden)

    Pangilinan Faith

    2012-08-01

    Full Text Available Abstract Background Neural tube defects (NTDs are common birth defects (~1 in 1000 pregnancies in the US and Europe that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T and MTHFD1 rs2236225 (R653Q have been found to increase NTD risk. We hypothesized that variants in additional folate/B12 pathway genes contribute to NTD risk. Methods A tagSNP approach was used to screen common variation in 82 candidate genes selected from the folate/B12 pathway and NTD mouse models. We initially genotyped polymorphisms in 320 Irish triads (NTD cases and their parents, including 301 cases and 341 Irish controls to perform case–control and family based association tests. Significantly associated polymorphisms were genotyped in a secondary set of 250 families that included 229 cases and 658 controls. The combined results for 1441 SNPs were used in a joint analysis to test for case and maternal effects. Results Nearly 70 SNPs in 30 genes were found to be associated with NTDs at the p MFTC, CDKN2A, ADA, PEMT, CUBN, GART, DNMT3A, MTHFD1 and T (Brachyury and included the known NTD risk factor MTHFD1 R653Q (rs2236225. The single strongest signal was observed in a new candidate, MFTC rs17803441 (OR = 1.61 [1.23-2.08], p = 0.0003 for the minor allele. Though nominally significant, these associations did not remain significant after correction for multiple hypothesis testing. Conclusions To our knowledge, with respect to sample size and scope of evaluation of candidate polymorphisms, this is the largest NTD genetic association study reported to date. The scale of the study and the stringency of correction are likely to have contributed to real associations failing to survive

  10. Detection of copy number variants reveals association of cilia genes with neural tube defects.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    Full Text Available BACKGROUND: Neural tube defects (NTDs are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. METHODS: The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. RESULTS: Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV. Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05. Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24-5.87. Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05, corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27-8.01. Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. CONCLUSIONS: Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.

  11. Functional complementation of a nitrate reductase defective mutant of a green alga Dunaliella viridis by introducing the nitrate reductase gene.

    Science.gov (United States)

    Sun, Yu; Gao, Xiaoshu; Li, Qiyun; Zhang, Qingqi; Xu, Zhengkai

    2006-08-01

    Nitrate reductase (NR) catalyzes NAD (P) H dependent reduction of nitrate to nitrite. Transformation systems have been established in several species of green algae by nitrate reductase gene functional complementation. In this report, an endogenous NR cDNA (3.4 kb) and a genomic fragment (14.6 kb) containing the NR gene (DvNIA1) were isolated from the D. viridis cDNA and genomic libraries respectively. Southern blot and Northern blot analyses showed that this gene exists as a single copy in D. viridis and is induced by nitrate. To obtain a NR defective mutant as a recipient strain, D. viridis cells were treated with a chemical mutagen and then cultured on a chlorate-containing plate to enrich chlorate tolerant mutants. Southern analysis showed that one isolate, B14, had a deletion in the DvNIA1 gene region. Using electroporation conditions determined in this laboratory, plasmid pDVNR containing the intact DvNIA1 gene has been electroporated into the defective mutant B14. Strains retaining a nitrate assimilation phenotype were obtained from nitrate plates after spreading the electroporated cells. In some individual strains, transcription of the introduced gene was detected. NR activity in these strains was slightly higher than that in the defective B14 cell, but excretion of nitrite into culture media was almost as high as that of the wild-type cell. Possible episomal presence of the introduced DNA in D. viridis is discussed. PMID:16797881

  12. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects

    Directory of Open Access Journals (Sweden)

    Shaw Gary M

    2009-06-01

    Full Text Available Abstract Background Folic acid taken in early pregnancy reduces risks for delivering offspring with several congenital anomalies. The mechanism by which folic acid reduces risk is unknown. Investigations into genetic variation that influences transport and metabolism of folate will help fill this data gap. We focused on 118 SNPs involved in folate transport and metabolism. Methods Using data from a California population-based registry, we investigated whether risks of spina bifida or conotruncal heart defects were influenced by 118 single nucleotide polymorphisms (SNPs associated with the complex folate pathway. This case-control study included 259 infants with spina bifida and a random sample of 359 nonmalformed control infants born during 1983–86 or 1994–95. It also included 214 infants with conotruncal heart defects born during 1983–86. Infant genotyping was performed blinded to case or control status using a designed SNPlex assay. We examined single SNP effects for each of the 118 SNPs, as well as haplotypes, for each of the two outcomes. Results Few odds ratios (ORs revealed sizable departures from 1.0. With respect to spina bifida, we observed ORs with 95% confidence intervals that did not include 1.0 for the following SNPs (heterozygous or homozygous relative to the reference genotype: BHMT (rs3733890 OR = 1.8 (1.1–3.1, CBS (rs2851391 OR = 2.0 (1.2–3.1; CBS (rs234713 OR = 2.9 (1.3–6.7; MTHFD1 (rs2236224 OR = 1.7 (1.1–2.7; MTHFD1 (hcv11462908 OR = 0.2 (0–0.9; MTHFD2 (rs702465 OR = 0.6 (0.4–0.9; MTHFD2 (rs7571842 OR = 0.6 (0.4–0.9; MTHFR (rs1801133 OR = 2.0 (1.2–3.1; MTRR (rs162036 OR = 3.0 (1.5–5.9; MTRR (rs10380 OR = 3.4 (1.6–7.1; MTRR (rs1801394 OR = 0.7 (0.5–0.9; MTRR (rs9332 OR = 2.7 (1.3–5.3; TYMS (rs2847149 OR = 2.2 (1.4–3.5; TYMS (rs1001761 OR = 2.4 (1.5–3.8; and TYMS (rs502396 OR = 2.1 (1.3–3.3. However, multiple SNPs observed for a given gene showed evidence of linkage disequilibrium indicating

  13. Neurophysiological defects and neuronal gene deregulation in Drosophila mir-124 mutants.

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    Kailiang Sun

    2012-02-01

    Full Text Available miR-124 is conserved in sequence and neuronal expression across the animal kingdom and is predicted to have hundreds of mRNA targets. Diverse defects in neural development and function were reported from miR-124 antisense studies in vertebrates, but a nematode knockout of mir-124 surprisingly lacked detectable phenotypes. To provide genetic insight from Drosophila, we deleted its single mir-124 locus and found that it is dispensable for gross aspects of neural specification and differentiation. On the other hand, we detected a variety of mutant phenotypes that were rescuable by a mir-124 genomic transgene, including short lifespan, increased dendrite variation, impaired larval locomotion, and aberrant synaptic release at the NMJ. These phenotypes reflect extensive requirements of miR-124 even under optimal culture conditions. Comparison of the transcriptomes of cells from wild-type and mir-124 mutant animals, purified on the basis of mir-124 promoter activity, revealed broad upregulation of direct miR-124 targets. However, in contrast to the proposed mutual exclusion model for miR-124 function, its functional targets were relatively highly expressed in miR-124-expressing cells and were not enriched in genes annotated with epidermal expression. A notable aspect of the direct miR-124 network was coordinate targeting of five positive components in the retrograde BMP signaling pathway, whose activation in neurons increases synaptic release at the NMJ, similar to mir-124 mutants. Derepression of the direct miR-124 target network also had many secondary effects, including over-activity of other post-transcriptional repressors and a net incomplete transition from a neuroblast to a neuronal gene expression signature. Altogether, these studies demonstrate complex consequences of miR-124 loss on neural gene expression and neurophysiology.

  14. Amelogenin gene influence on enamel defects of cleft lip and palate patients

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    Fernanda Veronese OLIVEIRA

    2014-08-01

    Full Text Available The aim of this study was to investigate the occurrence of mutations in the amelogenin gene (AMELX in patients with cleft lip and palate (CLP and enamel defects (ED. A total of 165 patients were divided into four groups: with CLP and ED (n=46, with CLP and without ED (n = 34, without CLP and with ED (n = 34, and without CLP or ED (n = 51. Genomic DNA was extracted from saliva followed by conducting a Polymerase Chain Reaction and direct DNA sequencing of exons 2 through 7 of AMELX. Mutations were found in 30% (n = 14, 35% (n = 12, 11% (n = 4 and 13% (n = 7 of the subjects from groups 1, 2, 3 and 4, respectively. Thirty seven mutations were detected and distributed throughout exons 2 (1 mutation – 2.7%, 6 (30 mutations – 81.08% and 7 (6 mutations – 16.22% of AMELX. No mutations were found in exons 3, 4 or 5. Of the 30 mutations found in exon 6, 43.34% (n = 13, 23.33% (n = 7, 13.33% (n = 4 and 20% (n = 6 were found in groups 1, 2, 3 and 4, respectively. c.261 C > T (rs2106416, a silent mutation, was detected in 26 subjects, and found more significantly (p = 0.003 in patients with CLP (groups 1 and 2 – 23.75%, compared with those without CLP (groups 3 and 4 – 8.23%. In the groups without ED, this silent mutation was also found more significantly (p = 0.032 among subjects with CLP (17.65% in group 2, compared with those without CLP (7.8% in group 4. In conclusion, this study suggested that AMELX may be a candidate gene for cleft lip and palate.

  15. Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice.

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    Tadafumi Yokoyama

    Full Text Available The Wiskott-Aldrich syndrome (WAS is a rare X-linked primary immunodeficiency characterized by recurrent infections, thrombocytopenia, eczema, and high incidence of malignancy and autoimmunity. The cellular mechanisms underlying autoimmune complications in WAS have been extensively studied; however, they remain incompletely defined. We investigated the characteristics of IL-10-producing CD19+CD1dhighCD5+ B cells (CD1dhighCD5+ Breg obtained from Was gene knockout (WKO mice and found that their numbers were significantly lower in these mice compared to wild type (WT controls. Moreover, we found a significant age-dependent reduction of the percentage of IL-10-expressing cells in WKO CD1dhighCD5+ Breg cells as compared to age-matched WT control mice. CD1dhighCD5+ Breg cells from older WKO mice did not suppress the in vitro production of inflammatory cytokines from activated CD4+ T cells. Interestingly, CD1dhighCD5+ Breg cells from older WKO mice displayed a basal activated phenotype which may prevent normal cellular responses, among which is the expression of IL-10. These defects may contribute to the susceptibility to autoimmunity with age in patients with WAS.

  16. Decreased blood riboflavin levels are correlated with defective expression of RFT2 gene in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Maynur Eli; De-Sheng Li; Wei-Wei Zhang; Bing Kong; Chen-Song Du; Maimaitiaili Wumar; Batur Mamtimin; Ilyar Sheyhidin; Ayshamgul Hasim

    2012-01-01

    AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2 (RFT2) gene expression in gastric carcinoma (GC) development.METHODS:High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC.Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue.RESULTS:A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane (0.398 ± 0.149 vs 1.479 ± 0.587; P =0.040).Tumors exhibited low RFT2 protein expression (75%,16.7%,8.3% and 0%for no RFT2 staining,weak staining,medium staining and strong staining,respectively),which was significantly lower than that in the normal mucous membrane (10%,16.7%,26.7% and 46.7% for no RFT2 staining,weak staining,medium staining and strong staining,respectively; P < 0.05).Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade.Moreover,a significantly decrease in Uyghur patients was observed compared with Han patients.However,other parameters-gender,tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression.Blood riboflavin levels were reverse correlated with development of GC (1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients; P < 0.05).A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients (x2 =2.619; P =0.019).CONCLUSION:Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC.

  17. Vacuolar invertase gene silencing in potato decreasing the frequency of sugar-end defects

    Science.gov (United States)

    Sugar-end defect is a tuber quality disorder and persistent problem for the French fry processing industry that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one e...

  18. Regional gene therapy of bone defects%骨缺损的局部基因治疗

    Institute of Scientific and Technical Information of China (English)

    徐卫东; 赵建国

    2007-01-01

    BACKGROUND:The regional gene therapy of bone defect is to transfer genes capable of accelerating bone healing into target cells, which will transcript the genes into mRNA and translate them into proteins, then the target cells will be stimulated to differentiate under the role of protein, and finally reach the purpose of accelerating bone healing by means of autocrine or paracrine. With the development of cell recombination technique, more and more genes of growth factors involved in the bone repairing have been successfully cloned, which make it possible to treat bone defect with gene therapy. The present status for the regional gene therapy of bone defect is summarized.DATA SOURCES: An online search in Pubmed database was undertaken to identify articles about the regional gene therapy of bone defect published in English from January 1965 to January 2006 by using keywords of "gene therapy,bone defect". Meanwhile, Chinese relevant articles published from January 2000 to January 2006 were searched in Wanfang database by using the same keywords in Chinese.STUDY SELECTION: The data were primarily checked, and the references of each article were looked up. Inclusive criteria: related to the regional gene therapy of bone defect. Exclusive criteria: repetitive study or Meta analysis.DATA EXTRACTrON: Totally 237 articles were collected, 32 of them were in accordance with the inclusive criteria, and the other 205 were old or repetitive ones. Of the 32 articles, 4 were about the selection of destination genes, 3 about the selection of target cells, 7 about the selection of gene expression vector, 3 about the methods of gene transfer, 4 about gene therapy combined with tissue engineering in treating bone defect, 5 about polygenes in treating bone defects, and 2 about the problems and prospects in the gene therapy of bone defect.DATA SYNTHESIS: The regional gene therapy of bone defect is a new technique developed base on the basic theoretical cognition of bone regeneration

  19. A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.

    Science.gov (United States)

    Kosugi, S; Bhayana, S; Dean, H J

    1999-09-01

    We previously reported nine children with an autosomally recessive form of congenital hypothyroidism due to an iodide transport defect in a large Hutterite family with extensive consanguinity living in central Canada. Since the original report, we have diagnosed congenital hypothyroidism by newborn TSH screening in 9 additional children from the family. We performed direct sequencing of the PCR products of each NIS (sodium/iodide symporter) gene exon with flanking introns amplified from genomic DNA extracted from peripheral blood cells of the patients. We identified a novel NIS gene mutation, G395R (Gly395-->Arg; GGA-->AGA), in 10 patients examined in the present study. All of the parents tested were heterozygous for the mutation, suggesting that the patients were homozygous. The mutation was located in the 10th transmembrane helix. Expression experiments by transfection of the mutant NIS complimentary DNA into COS-7 cells showed no perchlorate-sensitive iodide uptake, confirming that the mutation is the direct cause of the iodide transport defect in these patients. A patient who showed an intermediate saliva/serum technetium ratio (14.0; normal, > or = 20) and was considered to have a partial or less severe defect in the previous report (IX-24) did not have a NIS gene mutation. It is now possible to use gene diagnostics of this unique NIS mutation to identify patients with congenital hypothyroidism due to an iodide transport defect in this family and to determine the carrier state of potential parents for genetic counseling and arranging rapid and early diagnosis of their infants. PMID:10487695

  20. The Neurofibromatosis Type 2 Gene Product, merlin, Reverses the F-Actin Cytoskeletal Defects in Primary Human Schwannoma Cells

    OpenAIRE

    Bashour, Anne-Marie; Meng, J.-J.; Ip, Wallace; MacCollin, Mia; Ratner, Nancy

    2002-01-01

    Schwannoma tumors, which occur sporadically and in patients with neurofibromatosis, account for 8% of intracranial tumors and can only be treated by surgical removal. Most schwannomas have biallelic mutations in the NF2 tumor suppressor gene. We previously showed that schwannoma-derived Schwann cells exhibit membrane ruffling and aberrant cell spreading when plated onto laminin, indicative of fundamental F-actin cytoskeletal defects. Here we expand these observations to a large group of spora...

  1. "FAMILIAL DEFECTIVE APOLIPORROTEIN B 100: FREQUENCY OF R3500Q MUTATION OF APOLIPOROTEIN B GENE IN IRANIAN HYPERCHOLESTEROLEMIC PATIENTS"

    Directory of Open Access Journals (Sweden)

    P. Fard-Esfahani

    2005-06-01

    Full Text Available Familial defective apolipoprotein (apo B 100 (FDB causes early-onset coronary heart diseases (CHD. It is produced by R3500Q mutation of the apoB gene resulting in decreased binding of LDL to LDL receptor. We screened the apo B gene for R3500Q mutation in 130 hypercholesterolemic patients, among whom 30 patients met criteria of familial hypercholesterolemia (FH. The prevalence of R3500Q allele in this patient population was 0%. To obtain better estimation of mutation frequency, a broad survey is needed.

  2. An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

    Science.gov (United States)

    Ackerman, Christine; Locke, Adam E.; Feingold, Eleanor; Reshey, Benjamin; Espana, Karina; Thusberg, Janita; Mooney, Sean; Bean, Lora J.H.; Dooley, Kenneth J.; Cua, Clifford L.; Reeves, Roger H.; Sherman, Stephanie L.; Maslen, Cheryl L.

    2012-01-01

    About half of people with trisomy 21 have a congenital heart defect (CHD), whereas the remainder have a structurally normal heart, demonstrating that trisomy 21 is a significant risk factor but is not causal for abnormal heart development. Atrioventricular septal defects (AVSD) are the most commonly occurring heart defects in Down syndrome (DS), and ∼65% of all AVSD is associated with DS. We used a candidate-gene approach among individuals with DS and complete AVSD (cases = 141) and DS with no CHD (controls = 141) to determine whether rare genetic variants in genes involved in atrioventricular valvuloseptal morphogenesis contribute to AVSD in this sensitized population. We found a significant excess (p < 0.0001) of variants predicted to be deleterious in cases compared to controls. At the most stringent level of filtering, we found potentially damaging variants in nearly 20% of cases but fewer than 3% of controls. The variants with the highest probability of being damaging in cases only were found in six genes: COL6A1, COL6A2, CRELD1, FBLN2, FRZB, and GATA5. Several of the case-specific variants were recurrent in unrelated individuals, occurring in 10% of cases studied. No variants with an equal probability of being damaging were found in controls, demonstrating a highly specific association with AVSD. Of note, all of these genes are in the VEGF-A pathway, even though the candidate genes analyzed in this study represented numerous biochemical and developmental pathways, suggesting that rare variants in the VEGF-A pathway might contribute to the genetic underpinnings of AVSD in humans. PMID:23040494

  3. A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion

    Energy Technology Data Exchange (ETDEWEB)

    Blunt, T.; Priestley, A.; Hafezparast, M.; McMillan, T. [Univ. of Sussex, Brighton (United Kingdom)] [and others

    1995-11-20

    The Chinese hamster ovary xrs mutants are sensitive to ionizing radiation, defective in DNA double-strand break rejoining, and unable to carry out V(D)J recombination effectively. Recently, the gene defective in these mutants, XRCC5, has been shown to encode Ku80, a component of the Ku protein and DNA-dependent protein kinase. We present here a YAC contig involving 25 YACs mapping to the region 2q33-q34, which encompasses the XRCC5 gene. Eight new markers for this region of chromosome 2 are identified. YACs encoding the Ku80 gene were transferred to xrs cells by protoplast fusion, and complementation of all the defective phenotypes has been obtained with two YACs. We discuss the advantages and disadvantages of this approach as a strategy for cloning human genes complementing defective rodent cell lines. 44 refs., 2 figs., 4 tabs.

  4. Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Young, M.; Antonarakis, S.E. [Univ. of Geneva (Switzerland); Inaba, Hiroshi [Tokyo Medical College (Japan)] [and others

    1997-03-01

    Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A{sub 8}TA{sub 2} sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient`s plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) {open_quotes}ribosomal frameshifting{close_quotes} resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A{sub 10} instead of A{sub 8}TA{sub 2}, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. 36 refs., 6 figs.

  5. Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects.

    Science.gov (United States)

    Bosoi, Ciprian M; Capra, Valeria; Allache, Redouane; Trinh, Vincent Quoc-Huy; De Marco, Patrizia; Merello, Elisa; Drapeau, Pierre; Bassuk, Alexander G; Kibar, Zoha

    2011-12-01

    The planar cell polarity (PCP) pathway controls the process of convergent extension (CE) during gastrulation and neural tube closure, and has been implicated in the pathogenesis of neural tube defects (NTDs) in animal models and human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1 in these malformations. We screened this gene in 810 unrelated NTD patients and identified seven rare missense heterozygous mutations that were absent in all controls analyzed and predicted to be functionally deleterious using bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs and further expands our knowledge of the role of PCP genes in the pathogenesis of these malformations.

  6. Genetic variation in genes of folate metabolism and neural-tube defect risk.

    NARCIS (Netherlands)

    Linden, I.J. van der; Afman, L.A.; Heil, S.G.; Blom, H.J.

    2006-01-01

    Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50-70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C

  7. Genetic variation in genes of folate metabolism and neural-tube defect risk

    NARCIS (Netherlands)

    Linden, van der I.J.; Afman, L.A.; Heil, S.G.; Blom, H.J.

    2006-01-01

    Neural-tube defects (NTD) are common congenital malformations that can lead to severe disability or even death. Periconceptional supplementation with the B-vitamin folic acid has been demonstrated to prevent 50–70% of NTD cases. Since the identification of the first genetic risk factor of NTD, the C

  8. A Novel Cell Death Gene Acts to Repair Patterning Defects in Drosophila melanogaster

    OpenAIRE

    Tanaka, Kentaro M.; Takahashi, Aya; Fuse, Naoyuki; Takano-Shimizu-Kouno, Toshiyuki

    2014-01-01

    Cell death is a mechanism utilized by organisms to eliminate excess cells during development. Here, we describe a novel regulator of caspase-independent cell death, Mabiki (Mabi), that is involved in the repair of the head patterning defects caused by extra copies of bicoid in Drosophila melanogaster. Mabiki functions together with caspase-dependent cell death mechanisms to provide robustness during development.

  9. Identification of Pathogenicity-Related Genes in Biofilm-Defective Acidovorax citrulli by Transposon Tn5 Mutagenesis

    Directory of Open Access Journals (Sweden)

    Jinyan Luo

    2015-11-01

    Full Text Available Biofilm formation is important for virulence of a large number of plant pathogenic bacteria. Indeed, some virulence genes have been found to be involved in the formation of biofilm in bacterial fruit blotch pathogen Acidovorax citrulli. However, some virulent strains of A. citrulli were unable to format biofilm, indicating the complexity between biofilm formation and virulence. In this study, virulence-related genes were identified in the biofilm-defective strain A1 of A. citrulli by using Tn5 insertion, pathogenicity test, and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR. Results from this study indicated that 22 out of the obtained 301 mutants significantly decreased the virulence of strain A1 compared to the wild-type. Furthermore, sequence analysis indicated that the obtained 22 mutants were due to the insertion of Tn5 into eight genes, including Aave 4244 (cation diffusion facilitator family transporter, Aave 4286 (hypothetical protein, Aave 4189 (alpha/beta hydrolase fold, Aave 1911 (IMP dehydrogenase/GMP reductase domain, Aave 4383 (bacterial export proteins, family 1, Aave 4256 (Hsp70 protein, Aave 0003 (histidine kinase, DNA gyrase B, and HSP90-like ATPase, and Aave 2428 (pyridoxal-phosphate dependent enzyme. Furthermore, the growth of mutant Aave 2428 was unaffected and even increased by the change in incubation temperature, NaCl concentration and the pH of the LB broth, indicating that this gene may be directly involved in the bacterial virulence. Overall, the determination of the eight pathogenicity-related genes in strain A1 will be helpful to elucidate the pathogenesis of biofilm-defective A. citrulli.

  10. Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.

    Directory of Open Access Journals (Sweden)

    Tiziano Pramparo

    2011-03-01

    Full Text Available Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε, and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can

  11. Detection of Gene Alteration for Color Vision Defects by Polymerase Chain Reaction

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    According to the fact that the abnormalities of visual pigment genes were always involved in the changing of the exon 5, two oligonucleotide primers were designed to amplify the exon 5 of red pigment gene and green pigment gene. After electrophoresis of the PCR products digested with Rsal or Sau3A, the DNA fragments from the exon 5 of red pigment gene (RPG) and green pigment gene (GPG) were separated since there are different restriction endonuclease sites. On the other hand, we analyzed the exon 5 rela...

  12. Characterization of SMAD3 Gene Variants for Possible Roles in Ventricular Septal Defects and Other Congenital Heart Diseases.

    Directory of Open Access Journals (Sweden)

    Fei-Feng Li

    Full Text Available Nodal/TGF signaling pathway has an important effect at early stages of differentiation of human embryonic stem cells in directing them to develop into different embryonic lineages. SMAD3 is a key intracellular messenger regulating factor in the Nodal/TGF signaling pathway, playing important roles in embryonic and, particularly, cardiovascular system development. The aim of this work was to find evidence on whether SMAD3 variations might be associated with ventricular septal defects (VSD or other congenital heart diseases (CHD.We sequenced the SMAD3 gene for 372 Chinese Han CHD patients including 176 VSD patients and evaluated SNP rs2289263, which is located before the 5'UTR sequence of the gene. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0. The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.Three heterozygous variants in SMAD3 gene, rs2289263, rs35874463 and rs17228212, were identified. Statistical analyses showed that the rs2289263 variant located before the 5'UTR sequence of SMAD3 gene was associated with the risk of VSD (P value=0.013 <0.05.The SNP rs2289263 in the SMAD3 gene is associated with VSD in Chinese Han populations.

  13. Effect of vascular endothelial growth factor 165 gene transfection on bone defects and its mRNA expression in rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHAO Dong-mei; WANG Hai-bin; YANG Jia-feng; WU Shi-qing; LIU Jun-li; XU Fu-yu; QIU Li-ping; CAI Jing-long

    2007-01-01

    Background Gene therapy has been a hot spot in repair of bone defects in recent years. This study aimed to construct a recombinant plasmid pcDNA3.1-VEGF165, and to observe the effect of vascular endothelial growth factor 165 (VEGF165)gene therapy on bone defects in rabbits.Methods Total RNA was extracted from rabbit bone tissues. VEGF165 cDNA fragment was prepared by reverse transcription and the gene was cloned by polymerase chain reaction (PCR). Plasmid pMD18-T/VEGF165 combined with pcDNA3.1 was cloned to reconstruct pcDNA3.1-VEGF165 plasmid. Thirty New Zealand white rabbits weighing (2.50±0.13)kg were used to establish models of bone defects (1 cm in length) of the bilateral radii. The bone defects were repaired with absorbable gelatin sponge. After the operation, physiological sodium chloride solution was injected into the injured site in one of the forelegs of the rabbits as the control group, and pcDNA3.1-VEGF165 plasmid (0.2 ml, 200 ng)was injected into the opposite foreleg as the experiment groups. At weeks 1, 2, 4, 6, 8, and 12 after the treatments, the bones were examined by X-ray, and the specimens of the bone defects were collected, stained with HE, and observed under a light microscope. The expression of VEGF165 mRNA was examined by real-time quantitative polymerase chain reaction (RQ-PCR).Results The pcDNA3.1-VEGF165 plasmid with a correct sequence was constructed successfully. Postoperative X-ray found no difference between the two groups at week 1. In the experiment group, callus and synostosis were observed after 2 weeks, and osteosis structure was normal at week 12; these phenomena occurred much later in the control group.In the experiment group, HE staining showed a large amount of newly formed blood vessels after 2 weeks, a number of bone trabeculae with osteoblasts proliferation at 4 weeks, and fresh bone cortex and reformed medullary cavity at 12 weeks; whereas in the control group these structures formed in later phases. The VEGF165 mRNA in

  14. Cationized gelatin hydrogels mixed with plasmid DNA induce stronger and more sustained gene expression than atelocollagen at calvarial bone defects in vivo.

    Science.gov (United States)

    Komatsu, K; Shibata, T; Shimada, A; Ideno, H; Nakashima, K; Tabata, Y; Nifuji, A

    2016-01-01

    Gene transduction of exogenous factors at local sites in vivo is a promising approach to promote regeneration of tissue defects owing to its simplicity and capacity for expression of a variety of genes. Gene transduction by viral vectors is highly efficient; however, there are safety concerns associated with viruses. As a method for nonviral gene transduction, plasmid DNA delivery is safer and simpler, but requires an efficient carrier substance. Here, we aimed to develop a simple, efficient method for bone regeneration by gene transduction and to identify optimal conditions for plasmid DNA delivery at bone defect sites. We focused on carrier substances and compared the efficiencies of two collagen derivatives, atelocollagen, and gelatin hydrogel, as substrates for plasmid DNA delivery in vivo. To assess the efficiencies of these substrates, we examined exogenous expression of green fluorescence protein (GFP) by fluorescence microscopy, polymerase chain reaction, and immunohistochemistry. GFP expression at the bone defect site was higher when gelatin hydrogel was used as a substrate to deliver plasmids than when atelocollagen was used. Moreover, the gelatin hydrogel was almost completely absorbed at the defect site, whereas some atelocollagen remained. When a plasmid harboring bone morphogenic protein 2 was delivered with the substrate to bony defect sites, more new bone formation was observed in the gelatin group than in the atelocollagen group. These results suggested that the gelatin hydrogel was more efficient than atelocollagen as a substrate for local gene delivery and may be a superior material for induction of bone regeneration. PMID:26848778

  15. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy.

    NARCIS (Netherlands)

    Jongbloet, P.H.; Verbeek, A.L.M.; Heijer, M. den; Roeleveld, N.

    2008-01-01

    ABSTRACT: Several conditions apparent at birth, e.g., neural tube defects (NTDs) and cardiac anomalies, are associated with polymorphisms in folate-related genes, such as the 677C --> T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Similar associations have been established f

  16. A novel cell death gene acts to repair patterning defects in Drosophila melanogaster.

    Science.gov (United States)

    Tanaka, Kentaro M; Takahashi, Aya; Fuse, Naoyuki; Takano-Shimizu-Kouno, Toshiyuki

    2014-06-01

    Cell death is a mechanism utilized by organisms to eliminate excess cells during development. Here, we describe a novel regulator of caspase-independent cell death, Mabiki (Mabi), that is involved in the repair of the head patterning defects caused by extra copies of bicoid in Drosophila melanogaster. Mabiki functions together with caspase-dependent cell death mechanisms to provide robustness during development. PMID:24671768

  17. DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects.

    Science.gov (United States)

    Rochtus, Anne; Izzi, Benedetta; Vangeel, Elise; Louwette, Sophie; Wittevrongel, Christine; Lambrechts, Diether; Moreau, Yves; Winand, Raf; Verpoorten, Carla; Jansen, Katrien; Van Geet, Chris; Freson, Kathleen

    2015-01-01

    Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different HOX genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX clusters, 26 CpGs were differentially methylated (P-value 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the HOXA and HOXB clusters, with the most profound difference for 3 CpGs within the HOXB7 gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9-16.9%; P-value T genotype. Significant HOXB7 hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways.

  18. Genetic polymorphisms of the TYMS gene are not associated with congenital cardiac septal defects in a Han Chinese population.

    Directory of Open Access Journals (Sweden)

    Jian-Yuan Zhao

    Full Text Available BACKGROUND: Clinical research indicates that periconceptional administration of folic acid can reduce the occurrence of congenital cardiac septal defects (CCSDs. The vital roles of folate exhibits in three ways: the unique methyl donor for DNA expression regulation, the de novo biosynthesis of purine and pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate synthase (TYMS is the solo catalysis enzyme for the de novo synthesis of dTMP, which is the essential precursor of DNA biosynthesis and repair process. To examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs risk, we investigated whether genetic polymorphisms in the TYMS gene associated with the CCSDs in a Han Chinese population. METHOD: Polymorphisms in the noncoding region of TYMS were identified via direct sequencing in 32 unrelated individuals composed of half CCSDs and half control subjects. Nine SNPs and two insertion/deletion polymorphisms were genotyped from two independent case-control studies involving a total of 529 CCSDs patients and 876 healthy control participants. The associations were examined by both single polymorphism and haplotype tests using logistic regression. RESULT: We found that TYMS polymorphisms were not related to the altered CCSDs risk, and even to the changed risk of VSDs subgroup, when tested in both studied groups separately or in combination. In the haplotype analysis, there were no haplotypes significantly associated with risks for CCSDs either. CONCLUSION: Our results show no association between common genetic polymorphisms of the regulatory region of the TYMS gene and CCSDs in the Han Chinese population.

  19. Glycosylation defects and virulence phenotypes of Leishmania mexicana phosphomannomutase and dolicholphosphate-mannose synthase gene deletion mutants.

    Science.gov (United States)

    Garami, A; Mehlert, A; Ilg, T

    2001-12-01

    Leishmania parasites synthesize an abundance of mannose (Man)-containing glycoconjugates thought to be essential for virulence to the mammalian host and for viability. These glycoconjugates include lipophosphoglycan (LPG), proteophosphoglycans (PPGs), glycosylphosphatidylinositol (GPI)-anchored proteins, glycoinositolphospholipids (GIPLs), and N-glycans. A prerequisite for their biosynthesis is an ample supply of the Man donors GDP-Man and dolicholphosphate-Man. We have cloned from Leishmania mexicana the gene encoding the enzyme phosphomannomutase (PMM) and the previously described dolicholphosphate-Man synthase gene (DPMS) that are involved in Man activation. Surprisingly, gene deletion experiments resulted in viable parasite lines lacking the respective open reading frames (DeltaPMM and DeltaDPMS), a result against expectation and in contrast to the lethal phenotype observed in gene deletion experiments with fungi. L. mexicana DeltaDPMS exhibits a selective defect in LPG, protein GPI anchor, and GIPL biosynthesis, but despite the absence of these structures, which have been implicated in parasite virulence and viability, the mutant remains infectious to macrophages and mice. By contrast, L. mexicana DeltaPMM are largely devoid of all known Man-containing glycoconjugates and are unable to establish an infection in mouse macrophages or the living animal. Our results define Man activation leading to GDP-Man as a virulence pathway in Leishmania. PMID:11689705

  20. Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model.

    Science.gov (United States)

    Potash, Andrea E; Wallen, Tanner J; Karp, Philip H; Ernst, Sarah; Moninger, Thomas O; Gansemer, Nicholas D; Stoltz, David A; Zabner, Joseph; Chang, Eugene H

    2013-05-01

    Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis. PMID:23511247

  1. Disruption of polyubiquitin gene Ubc leads to defective proliferation of hepatocytes and bipotent fetal liver epithelial progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyejin; Yoon, Min-Sik; Ryu, Kwon-Yul, E-mail: kyryu@uos.ac.kr

    2013-06-07

    Highlights: •Proliferation capacity of Ubc{sup −/−} FLCs was reduced during culture in vitro. •Ubc is required for proliferation of both hepatocytes and bipotent FLEPCs. •Bipotent FLEPCs exhibit highest Ubc transcription and proliferation capacity. •Cell types responsible for Ubc{sup −/−} fetal liver developmental defect were identified. -- Abstract: We have previously demonstrated that disruption of polyubiquitin gene Ubc leads to mid-gestation embryonic lethality most likely due to a defect in fetal liver development, which can be partially rescued by ectopic expression of Ub. In a previous study, we assessed the cause of embryonic lethality with respect to the fetal liver hematopoietic system. We confirmed that Ubc{sup −/−} embryonic lethality could not be attributed to impaired function of hematopoietic stem cells, which raises the question of whether or not FLECs such as hepatocytes and bile duct cells, the most abundant cell types in the liver, are affected by disruption of Ubc and contribute to embryonic lethality. To answer this, we isolated FLCs from E13.5 embryos and cultured them in vitro. We found that proliferation capacity of Ubc{sup −/−} cells was significantly reduced compared to that of control cells, especially during the early culture period, however we did not observe the increased number of apoptotic cells. Furthermore, levels of Ub conjugate, but not free Ub, decreased upon disruption of Ubc expression in FLCs, and this could not be compensated for by upregulation of other poly- or mono-ubiquitin genes. Intriguingly, the highest Ubc expression levels throughout the entire culture period were observed in bipotent FLEPCs. Hepatocytes and bipotent FLEPCs were most affected by disruption of Ubc, resulting in defective proliferation as well as reduced cell numbers in vitro. These results suggest that defective proliferation of these cell types may contribute to severe reduction of fetal liver size and potentially mid

  2. Role of extracellular matrix and mitochondria related genes in determining cardiac defects in Down syndrome

    OpenAIRE

    Cicatiello, Rita

    2015-01-01

    Mitochondrial dysfunction, which is consistently observed in Down syndrome (DS), is suspected to worsen mental retardation and congenital cardiopathies in DS subjects, as well as to determine other phenotypic abnormalities, such as Alzheimer's disease, type 2 diabetes, obesity, and hypertrophic cardiopathy. As the heart is one of the main targets of DS, we have analyzed gene expression of DS fetal hearts demonstrating a global downregulation of nuclear encoded mitochondrial genes (NEMGs) ...

  3. Molecular cloning of a mouse DNA repair gene that complements the defect of group-A xeroderma pigmentosum

    International Nuclear Information System (INIS)

    For isolation of the gene responsible for xeroderma pigmentosum (XP) complementation group A, plasmid pSV2gpt and genomic DNA from a mouse embryo were cotransfected into XP2OSSV cells, a group-A XP cell line. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt-transformed XP colonies. pSV2gpt and genomic DNA from the primary transfectants were again cotransfected into XP2OSSV cells and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt-transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into an EMBL3 vector from the genome of a secondary transfectant. Transfections of the cloned DNA also conferred UV resistance on another group-A XP cell line but not on XP cell lines of group C, D, F, or G. Northern blot analysis of poly(A)+ RNA with a subfragment of cloned mouse DNA repair gene as the probe revealed that an approximately 1.0 kilobase mRNA was transcribed in the donor mouse embryo and secondary transfectant, and approximately 1.0- and approximately 1.3-kilobase mRNAs were transcribed in normal human cells, but none of these mRNAs was detected in three strains of group-A XP cells. These results suggest that the cloned DNA repair gene is specific for group-A XP and may be the mouse homologue of the group-A XP human gene

  4. Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene.

    Science.gov (United States)

    Gerards, Mike; van den Bosch, Bianca J C; Danhauser, Katharina; Serre, Valérie; van Weeghel, Michel; Wanders, Ronald J A; Nicolaes, Gerry A F; Sluiter, Wim; Schoonderwoerd, Kees; Scholte, Hans R; Prokisch, Holger; Rötig, Agnès; de Coo, Irenaeus F M; Smeets, Hubert J M

    2011-01-01

    Mitochondrial complex I deficiency is the most common oxidative phosphorylation defect. Mutations have been detected in mitochondrial and nuclear genes, but the genetics of many patients remain unresolved and new genes are probably involved. In a consanguineous family, patients presented easy fatigability, exercise intolerance and lactic acidosis in blood from early childhood. In muscle, subsarcolemmal mitochondrial proliferation and a severe complex I deficiency were observed. Exercise intolerance and complex I activity was improved by a supplement of riboflavin at high dosage. Homozygosity mapping revealed a candidate region on chromosome three containing six mitochondria-related genes. Four genes were screened for mutations and a homozygous substitution was identified in ACAD9 (c.1594 C>T), changing the highly conserved arginine-532 into tryptophan. This mutation was absent in 188 ethnically matched controls. Protein modelling suggested a functional effect due to the loss of a stabilizing hydrogen bond in an α-helix and a local flexibility change. To test whether the ACAD9 mutation caused the complex I deficiency, we transduced fibroblasts of patients with wild-type and mutant ACAD9. Wild-type, but not mutant, ACAD9 restored complex I activity. An unrelated patient with the same phenotype was compound heterozygous for c.380 G>A and c.1405 C>T, changing arginine-127 into glutamine and arginine-469 into tryptophan, respectively. These amino acids were highly conserved and the substitutions were not present in controls, making them very probably pathogenic. Our data support a new function for ACAD9 in complex I function, making this gene an important new candidate for patients with complex I deficiency, which could be improved by riboflavin treatment. PMID:20929961

  5. A novel peculiar mutation in the sodium/iodide symporter gene in spanish siblings with iodide transport defect.

    Science.gov (United States)

    Kosugi, Shinji; Okamoto, Hiroomi; Tamada, Aiko; Sanchez-Franco, F

    2002-08-01

    Previously, we reported two Spanish siblings with congenital hypothyroidism due to total failure of iodide transport. These were the only cases reported to date who received long-term iodide treatment over 10 yr. We examined the sodium/iodide symporter (NIS) gene of these patients. A large deletion was observed by long and accurate PCR using primers derived from introns 2 and 7 of the NIS gene. PCR-direct sequencing revealed a deletion of 6192 bases spanning from exon 3 to intron 7 and an inverted insertion of a 431-base fragment spanning from exon 5 to intron 5 of the NIS gene. The patients were homozygous for the mutation, and their mother was heterozygous. In the mutant, deletion of exons 3-7 was suggested by analysis using programs to predict exon/intron organization, resulting in an in-frame 182-amino acid deletion from Met(142) in the fourth transmembrane domain to Gln(323) in the fourth exoplasmic loop. The mutant showed no iodide uptake activity when transfected into COS-7 cells, confirming that the mutation was the direct cause of the iodide transport defect in these patients. Further, the mutant NIS protein was synthesized, but not properly expressed, on the cell surface, but was mostly accumulated in the cytoplasm, suggesting impaired targeting to the plasma membrane. PMID:12161518

  6. Mutations in the COPII vesicle component gene SEC24B are associated with human neural tube defects.

    Science.gov (United States)

    Yang, Xue-Yan; Zhou, Xiang-Yu; Wang, Qing Qing; Li, Hong; Chen, Ying; Lei, Yun-Ping; Ma, Xiao-Hang; Kong, Pan; Shi, Yan; Jin, Li; Zhang, Ting; Wang, Hong-Yan

    2013-08-01

    Neural tube defects (NTDs) are severe birth malformations that affect one in 1,000 live births. Recently, mutations in the planar cell polarity (PCP) pathway genes had been implicated in the pathogenesis of NTDs in both the mouse model and in human cohorts. Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis. In this study, we found four rare missense heterozygous SEC24B mutations (p.Phe227Ser, p.Phe682Leu, p.Arg1248Gln, and p.Ala1251Gly) in NTDs cases that were absent in all controls. Among them, p.Phe227Ser and p.Phe682Leu affected its protein stability and physical interaction with VANGL2. Three variants (p.Phe227Ser, p.Arg1248Gln, and p.Ala1251Gly) were demonstrated to affect VANGL2 subcellular localization in cultured cells. Further functional analysis in the zebrafish including overexpression and dosage-dependent rescue study suggested that these four mutations all displayed loss-of-function effects compared with wild-type SEC24B. Our study demonstrated that functional mutations in SEC24B might contribute to the etiology of a subset of human NTDs and further expanded our knowledge of the role of PCP pathway-related genes in the pathogenesis of human NTDs.

  7. Association of the GLI gene with ventricular septal defect after the susceptibility gene being narrowed to 3.56 cM in 12q13

    Institute of Scientific and Technical Information of China (English)

    QIU Guang-rong; GONG Li-guo; HE Guang; XU Xiao-yan; XIN Na; SUN Gui-feng; YUAN Yi-hua; SUN Kai-lai

    2006-01-01

    Background Our previous research has suggested that genes around D12S1056 in 12q13 may confer susceptibility to ventricular septal defect (VSD) in humans. The present study was to define the chromosome region assignment by transmission disequilibrium test (TDT), and to identify the important candidate gene by family-based association study and haplotype analysis. Methods Surrounding D12S1056, ten microsatellite markers including D12S329, D12S305, D12S1662, D12S1056, D12S1293, D12S334, D12S102, D12S83, D12S1655 and D12S1691 were chosen, and TDT was performed in 62 nuclear family trios each consisting of an affected child and two healty parents. Subsequently, the GLI gene, a positional candidate gene that maps to the target region, was selected for further analysis. Three single nucleotide polymorphisms (SNPs), G11888C, G11388A, and G11625T, were selected for family-based association study and haplotype analysis. Results VSD was significantly associated with all selected markers except D12S1691 [72.2 centi morgen (cM)] and D12S1700 (75.76 cM). VSD was also significantly associated with G11888C (χ2 = 5.918, P = 0.015), G11388A (χ2 = 8.067, P = 0.005), and G11625T (χ2 = 11.842, P = 0.001). Haplotype analysis showed a strong linkage disequilibrium between G11888C and G11388A (D'=0.999), but in significant (χ2 = 1.035, df = 2, P >0.05). Conclusions The susceptibility gene of VSD was mapped to 3.56 cM in 12q13 by TDT, and the GLI gene, an important candidate in the target region, was associated with VSD.

  8. A mutation in the Srrm4 gene causes alternative splicing defects and deafness in the Bronx waltzer mouse.

    Directory of Open Access Journals (Sweden)

    Yoko Nakano

    Full Text Available Sensory hair cells are essential for hearing and balance. Their development from epithelial precursors has been extensively characterized with respect to transcriptional regulation, but not in terms of posttranscriptional influences. Here we report on the identification and functional characterization of an alternative-splicing regulator whose inactivation is responsible for defective hair-cell development, deafness, and impaired balance in the spontaneous mutant Bronx waltzer (bv mouse. We used positional cloning and transgenic rescue to locate the bv mutation to the splicing factor-encoding gene Ser/Arg repetitive matrix 4 (Srrm4. Transcriptome-wide analysis of pre-mRNA splicing in the sensory patches of embryonic inner ears revealed that specific alternative exons were skipped at abnormally high rates in the bv mice. Minigene experiments in a heterologous expression system confirmed that these skipped exons require Srrm4 for inclusion into the mature mRNA. Sequence analysis and mutagenesis experiments showed that the affected transcripts share a novel motif that is necessary for the Srrm4-dependent alternative splicing. Functional annotations and protein-protein interaction data indicated that the encoded proteins cluster in the secretion and neurotransmission pathways. In addition, the splicing of a few transcriptional regulators was found to be Srrm4 dependent, and several of the genes known to be targeted by these regulators were expressed at reduced levels in the bv mice. Although Srrm4 expression was detected in neural tissues as well as hair cells, analyses of the bv mouse cerebellum and neocortex failed to detect splicing defects. Our data suggest that Srrm4 function is critical in the hearing and balance organs, but not in all neural tissues. Srrm4 is the first alternative-splicing regulator to be associated with hearing, and the analysis of bv mice provides exon-level insights into hair-cell development.

  9. Defective Regulation of MicroRNA Target Genes in Myoblasts from Facioscapulohumeral Dystrophy Patients*

    Science.gov (United States)

    Dmitriev, Petr; Stankevicins, Luiza; Ansseau, Eugenie; Petrov, Andrei; Barat, Ana; Dessen, Philippe; Robert, Thomas; Turki, Ahmed; Lazar, Vladimir; Labourer, Emmanuel; Belayew, Alexandra; Carnac, Gilles; Laoudj-Chenivesse, Dalila; Lipinski, Marc; Vassetzky, Yegor S.

    2013-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant hereditary neuromuscular disorder linked to the deletion of an integral number of 3.3-kb-long macrosatellite repeats (D4Z4) within the subtelomeric region of chromosome 4q. Most genes identified in this region are overexpressed in FSHD myoblasts, including the double homeobox genes DUX4 and DUX4c. We have carried out a simultaneous miRNome/transcriptome analysis of FSHD and control primary myoblasts. Of 365 microRNAs (miRNAs) analyzed in this study, 29 were found to be differentially expressed between FSHD and normal myoblasts. Twenty-one microRNAs (miR-1, miR-7, miR-15a, miR-22, miR-30e, miR-32, miR-107, miR-133a, miR-133b, miR-139, miR-152, miR-206, miR-223, miR-302b, miR-331, miR-362, miR-365, miR-382, miR-496, miR-532, miR-654, and miR-660) were up-regulated, and eight were down-regulated (miR-15b, miR-20b, miR-21, miR-25, miR-100, miR-155, miR-345, and miR-594). Twelve of the miRNAs up-regulated in FHSD were also up-regulated in the cells ectopically expressing DUX4c, suggesting that this gene could regulate miRNA gene transcription. The myogenic miRNAs miR-1, miR-133a, miR-133b, and miR-206 were highly expressed in FSHD myoblasts, which nonetheless did not prematurely enter myogenic differentiation. This could be accounted for by the fact that in FSHD myoblasts, functionally important target genes, including cell cycle, DNA damage, and ubiquitination-related genes, escape myogenic microRNA-induced repression. PMID:24145033

  10. Transfection of the cloned human excision repair gene ERCC-1 to UV-sensitive CHO mutants only corrects the repair defect in complementation group 2 mutants.

    NARCIS (Netherlands)

    M. van Duin (Mark); J.H. Janssen; J. de Wit (Jan); J.H.J. Hoeijmakers (Jan); L.H. Thompson; D. Bootsma (Dirk); A. Westerveld (Andries)

    1988-01-01

    textabstractThe human DNA-excision repair gene ERCC-1 is cloned by its ability to correct the excision-repair defect of the ultraviolet light- and mitomycin-C-sensitive CHO mutant cell line 43-3B. This mutant is assigned to complementation group 2 of the excision-repair-deficient CHO mutants. In ord

  11. Microphthalmia with linear skin defects syndrome (MLS): Characterization of the critical region and isolation of candidate genes

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, L.; Wapenaar, M.C.; Grillo, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder characterized by abnormalities in the development of the eye, skin, and brain. We defined the MLS critical region through analysis of hybrid cell lines retaining various deletion breakpoints in Xp22, including cell lines from 17 female patients showing features of MLS. Using a combination of YAC cloning and long-range restriction analysis, the MLS candidate region was estimated to be 450-550 kb. A minimally overlapping cosmid contig comprised of 20 cosmid clones was subsequently developed in this region. These cosmids are currently being used to isolate expressed sequences using cross-species conservation studies and exon-trapping. An evolutionarily conserved sequence isolated from a cosmid within the critical region has been used to isolate several overlapping cDNAs from a human embryonic library. Northern analysis using these cDNA clones identified a 5.2 kb transcript in all tissues examined. Sequence analysis revealed a 777 base pair open reading frame encoding a putative 258 amino acid protein. Using the exon-trapping method, fifty-four putative exons have been isolated from fourteen cosmids within the critical region. The expression patterns of the genes containing these exons are being analyzed by polymerase chain reaction (PCR) using reverse-transcribed mRNA from several human tissues and primers corresponding to the exon sequences. Using this approach in combination with exon connection, we determined the four of the trapped exons belong to the same cDNA transcript, which is expressed in adult retina, lymphoblast, skeletal muscle, and fetal brain. To date, we have isolated and sequenced 1 kilobase of this gene, all of which appears to be open reading frame. Both of the genes isolated from the critical region are being analyzed as possible candidates for MLS.

  12. Single nucleotide polymorphisms of the maternal Msx2 gene and their association with fetal neural tube defects in Han ethnic group in Shanxi Province, China

    Institute of Scientific and Technical Information of China (English)

    GUO Li; ZHAO Hong; PEI Yu-heng; HE Quan-ren; LI Wan-I; ZHANG Ting; ZHENG Xiao-ying; ZHOU Ran; XIE Jun

    2011-01-01

    Background Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population.Methods We studied 59 mothers with at least one previous child with a neural tube defect (the case group) and 73case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T poiymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests.Results Significant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups (CT: 32% vs. 15%, P=0.0073 and TT 15% vs. 4%, P=0.013, respectively). Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects (P <0.05; OR: 3.466;95%CI: 1.831-6.560). Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2.Conclusion Maternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.

  13. Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings.

    Science.gov (United States)

    Taché, Véronique; Bivina, Liga; White, Sophie; Gregg, Jeffrey; Deignan, Joshua; Boyadjievd, Simeon A; Poulain, Francis R

    2016-01-01

    A term male neonate developed severe intractable lactic acidosis on day of life 1 and died the same day at our institution. The family previously lost another term, female newborn on day of life 1 from suspected sepsis at an outside hospital. After performing an autopsy on the neonate who died at our institution, extensive and lengthy neonatal and parental genetic testing, as well as biochemical analyses, and whole exome sequencing analysis identified compound heterozygous mutations in the lipoyltransferase 1 (LIPT1) gene responsible for the lipoylation of the 2-keto dehydrogenase complexes in the proband. These mutations were also identified in the deceased sibling. The clinical manifestations of these two siblings are consistent with those recently described in two unrelated families with lactic acidosis due to LIPT1 mutations, an underrecognized and underreported cause of neonatal death. Conclusions. Our observations contribute to the delineation of a new autosomal recessive metabolic disorder, leading to neonatal death. Our case report also highlights the importance of an interdisciplinary team in solving challenging cases. PMID:27247813

  14. The Mycobacterium tuberculosis H37Ra gene MRA_1916 causes growth defects upon down-regulation.

    Science.gov (United States)

    Singh, Kumar Sachin; Singh, Sudheer Kumar

    2015-01-01

    D-amino acid oxidases play an important role in converting D-amino acids to their corresponding α-keto acids. MRA_1916 of Mycobacterium tuberculosis H37Ra (Mtb-Ra) is annotated to be a D-amino acid oxidase (DAO). However, not much information is available about its physiological role during Mtb-Ra growth and survival. The present study was taken-up to understand the role of DAO during different stages of growth and effect of its down-regulation on growth. Recombinant Mtb-Ra strains with DAO and GlcB (malate synthase: MRA_1848) gene knockdown were developed and their growth was studied using Microtiter Alamar Blue Assay (MABA) with glycerol, acetate and glycine as a carbon source. Ethyl bromopyruvate (BrP) was used as an inhibitor of GlcB. MABA study showed inhibition of wild-type (WT) and knockdowns in the presence of BrP (2.5mM). However, growth inhibition of WT was less noticeable at lower concentrations of BrP. Mtb-Ra with DAO knockdown showed poor utilization of glycine in the presence of BrP. The DAO localization study showed its prominent distribution in cytosolic fraction and to some extent in cell wall and membrane fractions. Growth profile of WT under oxygen and nutritional stress showed changes in expression of DAO, GlcB, PckA (phosphoenolpyruvate carboxykinase: MRA_0219) and GlyA1 (serine hydroxymethyltransferase: MRA_1104). PMID:26531045

  15. Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings

    Directory of Open Access Journals (Sweden)

    Véronique Taché

    2016-01-01

    Full Text Available A term male neonate developed severe intractable lactic acidosis on day of life 1 and died the same day at our institution. The family previously lost another term, female newborn on day of life 1 from suspected sepsis at an outside hospital. After performing an autopsy on the neonate who died at our institution, extensive and lengthy neonatal and parental genetic testing, as well as biochemical analyses, and whole exome sequencing analysis identified compound heterozygous mutations in the lipoyltransferase 1 (LIPT1 gene responsible for the lipoylation of the 2-keto dehydrogenase complexes in the proband. These mutations were also identified in the deceased sibling. The clinical manifestations of these two siblings are consistent with those recently described in two unrelated families with lactic acidosis due to LIPT1 mutations, an underrecognized and underreported cause of neonatal death. Conclusions. Our observations contribute to the delineation of a new autosomal recessive metabolic disorder, leading to neonatal death. Our case report also highlights the importance of an interdisciplinary team in solving challenging cases.

  16. Association between TGFBR2 gene polymorphisms and congenital heart defects in Han Chinese population.

    Science.gov (United States)

    Huang, Fuhua; Li, Li; Shen, Chong; Wang, Hairu; Chen, Jinfeng; Chen, Wen; Chen, Xin

    2014-10-31

    Antecedentes: Factor de crecimiento transformante receptor II (TGFBR2) es un componente clave de la via de señalización de TGF - .TGFBR2 puede ser detectado en la generación de corazón. Los embriones de ratón de TGFBR2 gene knockout mostraron defectos congénitos del corazon. Métodos: Hemos realizado un estudio de casos y controles para investigar la asociación entre polimorfismos del gen TGFBR2 y defectos congénitos del corazón en la población china han. 125 pacientes con defectos congénitos del corazón y 615 unrelated controles fueron reclutados. Marcado de dos polimorfismos de nucleótido único (tagsnps) en 5 ‘aguas arriba del gen TGFBR2 (rs6785358, - 3779a / g; rs764522, - 1444c / g) fueron seleccionados y genotipados por reacción en cadena de la polimerasa (PCR) - polimorfismos de longitud de fragmentos de restricción (RFLP) de ensayo. Resultados: Se observó una diferencia significativa en la distribución de genotipos entre pacientes con defectos congénitos del corazón y controles para SNP rs6785358 (P = 0043). La SNP rs6785358 el porteador del alelo G (AG / GG genotipo) mostraron un importante crecimiento y mayor riesgo de defectos congénitos del corazón en comparación con AA homocigotos (OR = 1.545, IC del 95%: 1.013–2.356). Más análisis por sexo estratificación indicó que los individuos con alelo G (AG / GG genotipo) para SNP rs6785358 tienen una mayor susceptibilidad a defectos congénitos del corazón (OR = 2.088, IC del 95%: 1.123-3.883, p = 0.019) en machos, pero no en las mujeres (OR = 1.195, IC del 95%: 0.666-2.146, p = 0.55). No hay significación estadística fue detectado en la distribución de los genotipos y frecuencias de alelos de SNP rs764522 entre pacientes y controles. Conclusión: Nuestros resultados sugieren que el SNP rs6785358 de gen TGFBR2 se asoció con un mayor riesgo de defectos congénitos del corazón en los chinos han hombres y más investigación estaría justificada.

  17. Genes associated with common variable immunodeficiency: one diagnosis to rule them all?

    Science.gov (United States)

    Bogaert, Delfien J A; Dullaers, Melissa; Lambrecht, Bart N; Vermaelen, Karim Y; De Baere, Elfride; Haerynck, Filomeen

    2016-09-01

    Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. CVID shows a considerable phenotypical and genetic heterogeneity. In contrast to many other primary immunodeficiencies, monogenic forms count for only 2-10% of patients with CVID. Genes that have been implicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2 With the increasing number of disease genes identified in CVID, it has become clear that CVID is an umbrella diagnosis and that many of these genetic defects cause distinct disease entities. Moreover, there is accumulating evidence that at least a subgroup of patients with CVID has a complex rather than a monogenic inheritance. This review aims to discuss current knowledge regarding the molecular genetic basis of CVID with an emphasis on the relationship with the clinical and immunological phenotype. PMID:27250108

  18. Splice-site mutations cause Rrp6-mediated nuclear retention of the unspliced RNAs and transcriptional down-regulation of the splicing-defective genes.

    Directory of Open Access Journals (Sweden)

    Andrea B Eberle

    Full Text Available BACKGROUND: Eukaryotic cells have developed surveillance mechanisms to prevent the expression of aberrant transcripts. An early surveillance checkpoint acts at the transcription site and prevents the release of mRNAs that carry processing defects. The exosome subunit Rrp6 is required for this checkpoint in Saccharomyces cerevisiae, but it is not known whether Rrp6 also plays a role in mRNA surveillance in higher eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an in vivo system to study nuclear mRNA surveillance in Drosophila melanogaster. We have produced S2 cells that express a human beta-globin gene with mutated splice sites in intron 2 (mut beta-globin. The transcripts encoded by the mut beta-globin gene are normally spliced at intron 1 but retain intron 2. The levels of the mut beta-globin transcripts are much lower than those of wild type (wt ss-globin mRNAs transcribed from the same promoter. We have compared the expression of the mut and wt beta-globin genes to investigate the mechanisms that down-regulate the production of defective mRNAs. Both wt and mut beta-globin transcripts are processed at the 3', but the mut beta-globin transcripts are less efficiently cleaved than the wt transcripts. Moreover, the mut beta-globin transcripts are less efficiently released from the transcription site, as shown by FISH, and this defect is restored by depletion of Rrp6 by RNAi. Furthermore, transcription of the mut beta-globin gene is significantly impaired as revealed by ChIP experiments that measure the association of the RNA polymerase II with the transcribed genes. We have also shown that the mut beta-globin gene shows reduced levels of H3K4me3. CONCLUSIONS/SIGNIFICANCE: Our results show that there are at least two surveillance responses that operate cotranscriptionally in insect cells and probably in all metazoans. One response requires Rrp6 and results in the inefficient release of defective mRNAs from the transcription site. The

  19. Ulnar ray defect in an infant with a 6q21;7q31.2 translocation: Further evidence of the existence of a limb defect gene in 6q21

    Energy Technology Data Exchange (ETDEWEB)

    Gurrieri, F.; Genuardi, M.; Pomponi, M.G. [Universita di Palermo (Italy)] [and others

    1995-01-30

    Ectrodactyly is a developmental defect of the distal limbs characterized by marked clinical variability and genetic heterogeneity, also reflected in the observation of different chromosome abnormalities nonrandomly associated with longitudinal postaxial limb deficiencies. The one most frequently found in patients with split hand-split foot (SHSF) involves chromosome band 7q22. Recently, structural anomalies of chromosome 6q21 have been reported in 2 unrelated patients with SHSF, suggesting that this region may also contain genes responsible for limb development. We report on a third patient who had a de novo, apparently balanced t(6;7)(q21;q31.2) translocation and bilateral ulnar aplasia with postaxial oligodactyly. In spite of the different phenotypic effects observed in these 3 patients, we consider our case as further evidence that genes in 6q21 may play a role in distal limb development. 8 refs., 3 figs.

  20. Down-regulation of IKKβ expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma.

    Science.gov (United States)

    Mieczkowski, Jakub; Kocyk, Marta; Nauman, Pawel; Gabrusiewicz, Konrad; Sielska, Małgorzata; Przanowski, Piotr; Maleszewska, Marta; Rajan, Wenson D; Pszczolkowska, Dominika; Tykocki, Tomasz; Grajkowska, Wieslawa; Kotulska, Katarzyna; Roszkowski, Marcin; Kostkiewicz, Boguslaw; Kaminska, Bozena

    2015-10-20

    Glioblastoma (GBM) is an aggressive malignancy associated with profound host immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival, angiogenesis and block immune responses both locally and systematically. Mechanisms responsible for immunological deficits in GBM patients are poorly understood. We analyzed immune/inflammatory gene expression in five datasets of low and high grade gliomas, and performed Gene Ontology and signaling pathway analyses to identify defective transcriptional responses. The expression of many immune/inflammatory response and TLR signaling pathway genes was reduced in high grade gliomas compared to low grade gliomas. In particular, we found the reduced expression of the IKBKB, a gene coding for IKKβ, which phosphorylates IκB proteins and represents a convergence point for most signal transduction pathways leading to NFκB activation. The reduced IKBKB expression and IKKβ levels in GBM tissues were demonstrated by qPCR, Western blotting and immunohistochemistry. The IKKβ expression was down-regulated in microglia/macrophages infiltrating glioblastoma. NFκB activation, prominent in microglia/macrophages infiltrating low grade gliomas, was reduced in microglia/macrophages in glioblastoma tissues. Down-regulation of IKBKB expression and NFκB signaling in microglia/macrophages infiltrating glioblastoma correlates with defective expression of immune/inflammatory genes and M2 polarization that may result in the global impairment of anti-tumor immune responses in glioblastoma.

  1. Vacuolar invertase gene silencing in potato (Solanum tuberosum L.) improves processing quality by decreasing the frequency of sugar-end defects.

    Science.gov (United States)

    Zhu, Xiaobiao; Richael, Craig; Chamberlain, Patrick; Busse, James S; Bussan, Alvin J; Jiang, Jiming; Bethke, Paul C

    2014-01-01

    Sugar-end defect is a tuber quality disorder and persistent problem for the French fry processing industry that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one end of the tuber. Reducing sugars produced by invertase form dark-colored Maillard reaction products during frying. Acrylamide is another Maillard reaction product formed from reducing sugars and acrylamide consumption has raised health concerns worldwide. Vacuolar invertase gene (VInv) expression was suppressed in cultivars Russet Burbank and Ranger Russet using RNA interference to determine if this approach could control sugar-end defect formation. Acid invertase activity and reducing sugar content decreased at both ends of tubers. Sugar-end defects and acrylamide in fried potato strips were strongly reduced in multiple transgenic potato lines. Thus vacuolar invertase silencing can minimize a long-standing French fry quality problem while providing consumers with attractive products that reduce health concerns related to dietary acrylamide. PMID:24695527

  2. Vacuolar invertase gene silencing in potato (Solanum tuberosum L.) improves processing quality by decreasing the frequency of sugar-end defects.

    Science.gov (United States)

    Zhu, Xiaobiao; Richael, Craig; Chamberlain, Patrick; Busse, James S; Bussan, Alvin J; Jiang, Jiming; Bethke, Paul C

    2014-01-01

    Sugar-end defect is a tuber quality disorder and persistent problem for the French fry processing industry that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one end of the tuber. Reducing sugars produced by invertase form dark-colored Maillard reaction products during frying. Acrylamide is another Maillard reaction product formed from reducing sugars and acrylamide consumption has raised health concerns worldwide. Vacuolar invertase gene (VInv) expression was suppressed in cultivars Russet Burbank and Ranger Russet using RNA interference to determine if this approach could control sugar-end defect formation. Acid invertase activity and reducing sugar content decreased at both ends of tubers. Sugar-end defects and acrylamide in fried potato strips were strongly reduced in multiple transgenic potato lines. Thus vacuolar invertase silencing can minimize a long-standing French fry quality problem while providing consumers with attractive products that reduce health concerns related to dietary acrylamide.

  3. Vacuolar invertase gene silencing in potato (Solanum tuberosum L. improves processing quality by decreasing the frequency of sugar-end defects.

    Directory of Open Access Journals (Sweden)

    Xiaobiao Zhu

    Full Text Available Sugar-end defect is a tuber quality disorder and persistent problem for the French fry processing industry that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one end of the tuber. Reducing sugars produced by invertase form dark-colored Maillard reaction products during frying. Acrylamide is another Maillard reaction product formed from reducing sugars and acrylamide consumption has raised health concerns worldwide. Vacuolar invertase gene (VInv expression was suppressed in cultivars Russet Burbank and Ranger Russet using RNA interference to determine if this approach could control sugar-end defect formation. Acid invertase activity and reducing sugar content decreased at both ends of tubers. Sugar-end defects and acrylamide in fried potato strips were strongly reduced in multiple transgenic potato lines. Thus vacuolar invertase silencing can minimize a long-standing French fry quality problem while providing consumers with attractive products that reduce health concerns related to dietary acrylamide.

  4. CRISPR-Mediated Slamf1Δ/Δ Slamf5Δ/Δ Slamf6Δ/Δ Triple Gene Disruption Reveals NKT Cell Defects but Not T Follicular Helper Cell Defects

    Science.gov (United States)

    Hu, Joyce K.; Crampton, Jordan C.; Locci, Michela; Crotty, Shane

    2016-01-01

    SAP (SH2D1A) is required intrinsically in CD4 T cells to generate germinal center responses and long-term humoral immunity. SAP binds to SLAM family receptors, including SLAM, CD84, and Ly108 to enhance cytokine secretion and sustained T cell:B cell adhesion, which both improve T follicular helper (Tfh) cell aid to germinal center (GC) B cells. To understand the overlapping roles of multiple SLAM family receptors in germinal center responses, Slamf1Δ/Δ Slamf5Δ/Δ Slamf6Δ/Δ triple gene disruption (Slamf1,5,6Δ/Δ) mice were generated using CRISPR-Cas9 gene editing to eliminate expression of SLAM (CD150), CD84, and Ly108, respectively. Gene targeting was highly efficient, with 6 of 6 alleles disrupted in 14 of 23 pups and the majority of alleles disrupted in the remaining pups. NKT cell differentiation in Slamf1,5,6Δ/Δ mice was defective, but not completely absent. The remaining NKT cells exhibited substantially increased 2B4 (SLAMF4) expression. Surprisingly, there were no overt defects in germinal center responses to acute viral infections or protein immunizations in Slamf1,5,6Δ/Δ mice, unlike Sh2d1a-/- mice. Similarly, in the context of a competitive environment, SLAM family receptor expressing GC Tfh cell, GC B cell, and plasma cell responses exhibited no advantages over Slamf1,5,6Δ/Δ cells. PMID:27223891

  5. [Mutants of bacterium Azospirillum brasilense Sp245 with Omegon insertion in mmsB or fabG genes of lipid metabolism are defective in motility and flagellation].

    Science.gov (United States)

    Kovtunov, E A; Shelud'ko, A V; Chernyshova, M P; Petrova, L P; Katsy, E I

    2013-11-01

    Bacteria Azospirillum brasilense have mixed flagellation: in addition to the polar flagellum, numerous lateral flagella are formed in their cells on medium with increased density. Flagella determine the active swimming and swarming capacities of azospirilla. Using A. brasilense Sp245 as an example, we showed that the Omegon-Km artificial transposon insertion into the chromosomal gene for 3-hydroxyisobutyrate dehydrogenase (mmsB) was concurrent with the appearance of significant defects in the formation of polar flagella and with the paralysis of lateral flagella. The Sp245 mutant with the Omegon insertion into the plasmid AZOBR_p1-borne gene for 3-oxoacyl-[acyl-carrier protein]-reductase (fabG) showed the complete loss of flagella and the swarming capacity, as well as significant defects in polar flagellar assembly (though some cells are still motile in liquid medium). The viability of the A. brasilense Sp245 mutants with the Omegon insertion into the mmsB or fabG gene was not reduced. No considerable differences in the fatty acid composition of whole cell lipid extracts were found for the A. brasilense Sp245 strain and its mmsB and fabG mutants.

  6. Isolation, characterization and genetic analysis of canine GATA4 gene in a family of Doberman Pinschers with an atrial septal defect

    Indian Academy of Sciences (India)

    Shin-Aeh Lee; Seung-Gon Lee; Hyeong-Sun Moon; Lopeti Lavulo; Kyoung-Oh Cho; Changbaig Hyun

    2007-12-01

    GATA4 is expressed early in the developing heart where it plays a key role in regulating the expression of genes encoding myocardial contractile proteins. Gene mutations in the human GATA4 have been implicated in various congenital heart defects (CHD), including atrial septal defect (ASD). Although ASD is the third most common CHD in humans, it is generally rare in dogs and cats. There is also no obvious predilection for ASD in dogs and cats, based on sex or breed. However, among dogs, the incidence rate of ASD is relatively high in Samoyeds and Doberman Pinschers, where its inheritance and genetic aetiology are not well understood. In this study, we identified and investigated the genetic aetiology of an ASD affected family in a pure breed dog population. Although the GATA4 gene was screened, we did not find any mutations that would result in the alteration of the coding sequence and hence, the predicted GATA4 structure and function. Although the aetiology of ASD is multifactorial, our findings indicate that GATA4 may not be responsible for the ASD in the dogs used in this study. However, this does not eliminate GATA4 as a candidate for ASD in other dog breeds.

  7. The S haplotype-specific F-box protein gene, SFB, is defective in self-compatible haplotypes of Prunus avium and P. mume.

    Science.gov (United States)

    Ushijima, Koichiro; Yamane, Hisayo; Watari, Akiko; Kakehi, Eiko; Ikeda, Kazuo; Hauck, Nathanael R; Iezzoni, Amy F; Tao, Ryutaro

    2004-08-01

    Many Prunus species, including sweet cherry and Japanese apricot, of the Rosaceae, display an S-RNase-based gametophytic self-incompatibility (GSI). The specificity of this outcrossing mechanism is determined by a minimum of two genes that are located in a multigene complex, termed the S locus, which controls the pistil and pollen specificities. SFB, a gene located in the S locus region, encodes an F-box protein that has appropriate S haplotype-specific variation to be the pollen determinant in the self-incompatibility reaction. This study characterizes SFBs of two self-compatible (SC) haplotypes, S(4') and S(f), of Prunus. S(4') of sweet cherry is a pollen-part mutant (PPM) that was produced by X-ray irradiation, while S(f) of Japanese apricot is a naturally occurring SC haplotype that is considered to be a PPM. DNA sequence analysis revealed defects in both SFB(4') and SFB(f). A 4 bp deletion upstream from the HVa coding region of SFB(4') causes a frame-shift that produces transcripts of a defective SFB lacking the two hypervariable regions, HVa and HVb. Similarly, the presence of a 6.8 kbp insertion in the middle of the SFB(f) coding region leads to transcripts for a defective SFB lacking the C-terminal half that contains HVa and HVb. As all reported SFBs of functional S haplotypes encode intact SFB, the fact that the partial loss-of-function mutations in SFB are present in SC mutant haplotypes of Prunus provides additional evidence that SFB is the pollen S gene in GSI in Prunus. PMID:15272875

  8. A case report of primary ciliary dyskinesia, laterality defects and developmental delay caused by the co-existence of a single gene and chromosome disorder.

    LENUS (Irish Health Repository)

    Casey, Jillian P

    2015-01-01

    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterised by abnormal ciliary motion and impaired mucociliary clearance, leading to recurrent respiratory infections, sinusitis, otitis media and male infertility. Some patients also have laterality defects. We recently reported the identification of three disease-causing PCD genes in the Irish Traveller population; RSPH4A, DYX1C1 and CCNO. We have since assessed an additional Irish Traveller family with a complex phenotype involving PCD who did not have any of the previously identified PCD mutations.

  9. Defect modelling

    International Nuclear Information System (INIS)

    Calculations, drawing principally on developments at AERE Harwell, of the relaxation about lattice defects are reviewed with emphasis on the techniques required for such calculations. The principles of defect modelling are outlined and various programs developed for defect simulations are discussed. Particular calculations for metals, ionic crystals and oxides, are considered. (UK)

  10. The rise of the photosynthetic rate when light intensity increases is delayed in ndh gene-defective tobacco at high but not at low CO2 concentrations

    Directory of Open Access Journals (Sweden)

    Mercedes eMartin

    2015-02-01

    Full Text Available The 11 plastid ndh genes have hovered frequently on the edge of dispensability, being absent in the plastid DNA of many algae and certain higher plants. We have compared the photosynthetic activity of tobacco (Nicotiana tabacum, cv. Petit Havana with five transgenic lines (ndhF, pr-ndhF, T181D, T181A and ndhF FC and found that photosynthetic performance is impaired in transgenic ndhF-defective tobacco plants at rapidly fluctuating light intensities and higher than ambient CO2 concentrations. In contrast to wild type and ndhF FC, which reach the maximum photosynthetic rate in less than one min when light intensity suddenly increases, ndh defective plants (ndhF and T181A show up to a 5 min delay in reaching the maximum photosynthetic rate at CO2 concentrations higher than the ambient 360 ppm. Net photosynthesis was determined at different CO2 concentrations when sequences of 130, 870, 61, 870 and 130 μmol m−2 s−1 PAR sudden light changes were applied to leaves and photosynthetic efficiency and entropy production were determined as indicators of photosynthesis performance. The two ndh-defective plants, ndhF and T181A, had lower photosynthetic efficiency and higher entropy production than wt, ndhF FC and T181D tobacco plants, containing full functional ndh genes, at CO2 concentrations above 400 ppm. We propose that the Ndh complex improves cyclic electron transport by adjusting the redox level of transporters during the low light intensity stage. In ndhF-defective strains, the supply of electrons through the Ndh complex fails, transporters remain over-oxidized (specially at high CO2 concentrations and the rate of cyclic electron transport is low, impairing the ATP level required to rapidly reach high CO2 fixation rates in the following high light phase. Hence, ndh genes could be dispensable at low but not at high atmospheric concentrations of CO2.

  11. Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

    Directory of Open Access Journals (Sweden)

    Dokter Wim

    2010-06-01

    Full Text Available Abstract Background Glucocorticoids (GCs control expression of a large number of genes via binding to the GC receptor (GR. Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT and mice that have lost the ability to form GR dimers (GRdim. Results The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions This study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

  12. Mutations in the unc-52 gene responsible for body wall muscle defects in adult Caenorhabditis elegans are located in alternatively spliced exons

    Energy Technology Data Exchange (ETDEWEB)

    Rogalski, T.M.; Gilchrist, E.J.; Mullen, G.P. [Univ. of British, Columbia, Vancouver (Canada)] [and others

    1995-01-01

    The unc-52 gene in Caenorhabditis elegans produces several large proteins that function in the basement membrane underlying muscle cells. Mutations in this gene result in defects in myofilament assembly and in the attachment of the myofilament lattice to the muscle cell membrane. The st549 and ut111 alleles of unc-52 produce a lethal (Pat) terminal phenotype whereas the e444, e669, e998, e1012 and e1421 mutations result in viable, paralyzed animals. We have identified the sequence alterations responsible for these mutant phenotypes. The st549 allele has a premature stop codon in exon 7 that should result in the complete elimination of unc-52 gene function, and the ut111 allele has a Tc1 transposon inserted into the second exon of the gene. The five remaining mutations are clustered in a small interval containing three adjacent, alternatively spliced exons (16, 17 and 18). These mutations affect some, but not all of the unc-52-encoded proteins. Thirteen intragenic revertants of the e669, e998, e1012 and e1421 alleles have also been sequenced. The majority of these carry the original mutation plus a G to A transition in the conserved splice acceptor site of the affected exon. This result suggests that reversion of the mutant phenotype in these strains may be the result of exon-skipping. 38 refs., 6 figs., 2 tabs.

  13. Cloning of the Full-length cDNA of the Wheat Involved in Salt Stress: Root Hair Defective 3 Gene (RHD3)

    Institute of Scientific and Technical Information of China (English)

    Lei SHAN; Shuang-Yi ZHAO; Guang-Min XIA

    2005-01-01

    The full-length cDNA of the wheat (Triticum aestivum L.) root hair defective 3 gene (RHD3) has been cloned from the salt-tolerant hybrid wheat variety Shanrong No. 3 (Za3) using the mRNA differential display and 5′ rapid amplification of cDNA ends (RACE) methods. Analysis of the amino acid sequence deduced from the wheat RHD3 gene shows that two conservative GTP-binding motifs, namely GXXXXGKS and DXXG, in eukaryotes also exist at the N-terminal of wheat RHD3. In addition, an 18 amino acid residue transmembrane domain, namely FYLAVMFVVFLVGKAIWV, exists at positions 701-718 of the C-terminal of the deduced protein of wheat RHD3 obtained, but this domain is absent in another three proteins aligned,including rice RHD3, Arabidopsis RHD3, and yeast homologue SEY1. Northern blot revealed that transcription of the wheat RHD3 gene is down-regulated in both the salt-tolerant line and in JN177 under saline stress. A possible stress-responsive mechanism for this gene is discussed.

  14. Production of host shutoff-defective mutants of herpes simplex virus type 1 by inactivation of the UL13 gene.

    Science.gov (United States)

    Overton, H; McMillan, D; Hope, L; Wong-Kai-In, P

    1994-07-01

    Two mutants of HSV-1(SC16) carrying disrupted UL13 genes have been generated independently by recombination of wild-type genomic DNA with a plasmid-cloned copy of the UL13 gene containing multiple stop codons. The two mutants were shown to be deficient in UL13 gene expression by Western blotting of infected cells. A revertant virus, in which UL13 expression was restored to a near-normal level, was generated by recombination of one of the UL13-negative mutants with a plasmid carrying the wild-type UL13 gene. The replication of the two UL13-negative viruses in cell culture was somewhat reduced compared to their wild-type parent, and the viruses were unable to produce shutoff of host protein synthesis. The replication of the revertant virus was intermediate between that of the UL13-negative and wild-type viruses, as was its ability to produce host shutoff. Cells infected with the UL13-negative mutants were shown to contain much lower levels than normal of the UL41 gene product, which is known to be required for virion host shutoff. However, there was no significant difference between levels of the UL41 gene product in wild-type and mutant virions. The UL13-negative viruses exhibited different patterns of protein phosphorylation from wild-type virus when infected cells were metabolically labeled with [32P]-orthophosphate and when lysates of infected cells and of virions were subjected to in vitro phosphorylation. However, the UL41 gene product could still be phosphorylated in lysates of UL13-negative virions. We conclude that the UL13 gene is necessary to produce the virion host shutoff effect, but it seems unlikely that the role of UL13 is simply to activate the UL41 gene product by phosphorylation.

  15. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.

    Directory of Open Access Journals (Sweden)

    Noa Safra

    Full Text Available Neural tube defects (NTDs is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5, after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525 were found to be significantly over-represented (p=0.036. This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.

  16. Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS)

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, L.; Ballabio, A.; Zoghbi, H.Y. [Baylor College of Medicine, Houston, TX (United States)

    1996-06-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder associated with X chromosomal rearrangements resulting in monosomy from Xpter to Xp22. Features include microphthalmia, sclerocornea, linear skin defects, and agenesis of the corpus callosum. Using a cross-species conservation strategy, an expressed sequence from the 450- to the 550-kb MLS critical region on Xp22 was identified by screening a human embryo cDNA library. Northern analysis revealed a transcript of {approx}2.6 kb in all tissues examined, with weaker expression of {approx}1.2- and {approx}5.2-kb transcripts. The strongest expression was observed in heart and skeletal muscle. Sequence analysis of a 3-kb cDNA contig revealed an 807-bp open reading frame encoding a putative 268-amino-acid-protein. Comparison of the sequence with sequences in the databases revealed homology with holocytochrome c-type synthetases, which catalyze the covalent addition of a heme group onto c-type cytochromes in the mitochondria. The c-type cytochromes are required for proper functioning of the electron transport pathway. The human gene (HGMW-approved symbol HCCS) and the corresponding murine gene characterized in this paper are the first mammalian holocytochrome c-type synthetases to be described in the literature. Because of the lack of a neuromuscular phenotype in MLS, it is uncertain whether the deletion of a mitochondrial holocytochrome synthetase would contribute to the phenotype seen in MLS. The expression pattern of this gene and knowledge about the function of holocytochrome synthetases, however, suggest that it is a good candidate for X-linked encephalomyopathies typically associated with mitochondrial dysfunction. 25 refs., 4 figs.

  17. Deregulation of the OsmiR160 Target Gene OsARF18 Causes Growth and Developmental Defects with an Alteration of Auxin Signaling in Rice.

    Science.gov (United States)

    Huang, Jian; Li, Zhiyong; Zhao, Dazhong

    2016-01-01

    MicroRNAs (miRNAs) control gene expression as key negative regulators at the post-transcriptional level. MiR160 plays a pivotal role in Arabidopsis growth and development through repressing expression of its target AUXIN RESPONSE FACTOR (ARF) genes; however, the function of miR160 in monocots remains elusive. In this study, we found that the mature rice miR160 (OsmiR160) was mainly derived from OsMIR160a and OsMIR160b genes. Among four potential OsmiR160 target OsARF genes, the OsARF18 transcript was cleaved at the OsmiR160 target site. Rice transgenic plants (named mOsARF18) expressing an OsmiR160-resistant version of OsARF18 exhibited pleiotropic defects in growth and development, including dwarf stature, rolled leaves, and small seeds. mOsARF18 leaves were abnormal in bulliform cell differentiation and epidermal cell division. Starch accumulation in mOsARF18 seeds was also reduced. Moreover, auxin induced expression of OsMIR160a, OsMIR160b, and OsARF18, whereas expression of OsMIR160a and OsMIR160b as well as genes involved in auxin signaling was altered in mOsARF18 plants. Our results show that negative regulation of OsARF18 expression by OsmiR160 is critical for rice growth and development via affecting auxin signaling, which will advance future studies on the molecular mechanism by which miR160 fine-tunes auxin signaling in plants. PMID:27444058

  18. Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease

    Institute of Scientific and Technical Information of China (English)

    He Shulan; Tan Wuhong; Wang Sen; Wu Cuiyan; Wang Pan; Wang Bin; Su Xiaohui

    2014-01-01

    Background Keshan disease (KD) is an endemic cardiomyopathy in China.The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease.Young women of child-bearing age are the most frequent victims in rural areas.The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.Methods We extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men).Then the isolated RNA was amplified,labeled and hybridized to Agilent human 4×44k whole genome microarrays.Gene expression was examined using oligonucleotide microarray analysis.A quantitative polymerase chain reaction assay was also performed to validate our microarray results.Results Among the genes differentially expressed in female KD patients we identified:HLA-DOA,HLA-DRA,and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7,involved in cardiomyocyte differentiation defect; and ADAMTS 8,CCL23,and TNFSF15,implicated in anti-angiogenic activities.These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.Conclusion Our results might help to explain the higher susceptibility of women to this disease.

  19. Carbon allocation and element composition in four Chlamydomonas mutants defective in genes related to the CO2 concentrating mechanism.

    Science.gov (United States)

    Memmola, Francesco; Mukherjee, Bratati; Moroney, James V; Giordano, Mario

    2014-09-01

    Four mutants of Chlamydomonas reinhardtii with defects in different components of the CO2 concentrating mechanism (CCM) or in Rubisco activase were grown autotrophically at high pCO2 and then transferred to low pCO2, in order to study the role of different components of the CCM on carbon allocation and elemental composition. To study carbon allocation, we measured the relative size of the main organic pools by Fourier Transform Infrared spectroscopy. Total reflection X-ray fluorescence was used to analyze the elemental composition of algal cells. Our data show that although the organic pools increased their size at high CO2 in all strains, their stoichiometry was highly homeostatic, i.e., the ratios between carbohydrates and proteins, lipid and proteins, and carbohydrates and lipids, did not change significantly. The only exception was the wild-type 137c, in which proteins decreased relative to carbohydrates and lipids, when the cells were transferred to low CO2. It is noticeable that the two wild types used in this study responded differently to the transition from high to low CO2. Malfunctions of the CCM influenced the concentration of several elements, somewhat altering cell elemental stoichiometry: especially the C/P and N/P ratios changed appreciably in almost all strains as a function of the growth CO2 concentration, except in 137c and the Rubisco activase mutant rca1. In strain cia3, defective in the lumenal carbonic anhydrase (CA), the cell quotas of P, S, Ca, Mn, Fe, and Zn were about 5-fold higher at low CO2 than at high CO2. A Principle Components Analysis showed that, mostly because of its elemental composition, cia3 behaved in a substantially different way from all other strains, at low CO2. The lumenal CA thus plays a crucial role, not only for the correct functioning of the CCM, but also for element utilization. Not surprisingly, growth at high CO2 attenuated differences among strains.

  20. Molecular basis of the clotting defect in a bleeding patient missing the Asp-185 codon in the factor X gene.

    Science.gov (United States)

    Lu, Qiuya; Yang, Likui; Manithody, Chandrashekhara; Wang, Xuefeng; Rezaie, Alireza R

    2014-11-01

    Factor X (FX) is a vitamin K-dependent plasma zymogen, which following activation to factor Xa (FXa), converts prothrombin to thrombin in the blood clotting cascade. It was recently demonstrated that a natural variant of FX carrying the Asp-185 deletion (FX-D185del, chymotrypsinogen numbering) was associated with mild bleeding in a patient with severe FX deficiency. In this study, we expressed FX-D185del in mammalian cells and characterized its properties in appropriate kinetic assays in purified systems. We discovered that while the FX variant can be normally activated by physiological activators; both amidolytic and proteolytic activities of the mutant are dramatically impaired. Interestingly, factor Va (FVa) significantly improved the proteolytic defect when the mutant protease was assembled into the prothrombinase complex. Thus, in contrast to >50-fold catalytic defect in the absence of FVa, the variant activated prothrombin with only ~2.5-fold decreased catalytic efficiency in the presence of the cofactor. The FXa variant dramatically lost its susceptibility to inhibition by antithrombin and tissue factor pathway inhibitor, thus exhibiting ~2-3 orders of magnitude lower reactivity with the plasma inhibitors. Further studies revealed that Na(+) no longer activates the variant protease, suggesting that the functionally important allosteric linkage between the Na(+)-binding and the P1-binding sites of the protease has been eliminated. These results suggest that the lower catalytic efficiency of FXa-D185del in the bleeding patient may be partially compensated by the loss of its reactivity with plasma inhibitors, possibly explaining the basis for the paradoxical severe FX deficiency with only mild bleeding tendency for this mutation. PMID:25179519

  1. A Gene(s) for All-trans-Retinoic Acid-Induced Forelimb Defects Mapped and Confirmed to Murine Chromosome 11

    OpenAIRE

    Lee, Grace S.; Cantor, Rita M.; Abnoosian, Arin; Park, Euisun; Yamamoto, Mitsuko L.; Hovland, David N.; Collins, Michael D.

    2005-01-01

    All-trans-retinoic acid (RA) induces various anatomical limb dysmorphologies in mice dependent on the time of exposure. During early limb development, RA induces forelimb ectrodactyly (digital absence) with varying susceptibilities for different inbred mouse strains; C57BL/6N are highly susceptible while SWV are resistant. To isolate the genetic basis of this defect, a full-genome scan was performed in 406 backcross fetuses of F1 males to C57BL/6N females. Fetuses were exposed via a maternal ...

  2. Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people

    International Nuclear Information System (INIS)

    The frequency of mutant T lymphocytes defective in T-cell receptor gene (α or β) expression was measured using the two-color flow cytometric technique. Results for a total of 203 atomic bomb survivors, 78 of whom were proximally exposed (DS86 doses of ≥ 1.5 Gy) and 125 of whom were distally exposed (DS86 doses of 228Th formerly used for radiodiagnosis. In addition, thyroid disease patients treated with 131I showed a dose-related increase of mutant frequency. It was suggested that the present T-cell receptor mutation assay has a unique characteristic as a biological dosimeter for the measurement of recent exposures to genotoxic agents. (author)

  3. Effects of low-level laser therapy on the expression of osteogenic genes related in the initial stages of bone defects in rats

    Science.gov (United States)

    Fernandes, Kelly Rossetti; Ribeiro, Daniel Araki; Rodrigues, Natália Camargo; Tim, Carla; Santos, Anderson Amaro; Parizotto, Nivaldo Antônio; de Araujo, Heloisa Selistre; Driusso, Patrícia; Rennó, Ana Claudia Muniz

    2013-03-01

    We evaluate the effects of low-level laser therapy (LLLT) on the histological modifications and temporal osteogenic genes expression during the initial phase of bone healing in a model of bone defect in rats. Sixty-four Wistar rats were divided into control and treated groups. Noncritical size bone defects were surgically created at the upper third of the tibia. Laser irradiation (Ga-Al-As laser 830 nm, 30 mW, 0.028 cm2, 1.071 W/cm2, 1 min and 34 s, 2.8 Joules, 100 J/cm2) was performed for 1, 2, 3, and 5 sessions. Histopathology revealed that treated animals presented higher inflammatory cells recruitment, especially 12 and 36 h postsurgery. Also, a better tissue organization at the site of the injury, with the presence of granulation tissue and new bone formation was observed on days three and five postsurgery in the treated animals. The quantitative real time polymerase chain reaction showed that LLLT produced a significantly increase in mRNA expression of Runx-2, 12 h and three days post-surgery, a significant upregulation of alkaline phosphatase mRNA expression after 36 h and three days post-surgery and a significant increase of osteocalcin mRNA expression after three and five days. We concluded that LLLT modulated the inflammatory process and accelerated bone repair, and this advanced repair pattern in the laser-treated groups may be related to the higher mRNA expression of genes presented by these animals.

  4. Canine hereditary ataxia in old english sheepdogs and gordon setters is associated with a defect in the autophagy gene encoding RAB24.

    Directory of Open Access Journals (Sweden)

    Caryline Agler

    2014-02-01

    Full Text Available Old English Sheepdogs and Gordon Setters suffer from a juvenile onset, autosomal recessive form of canine hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex. The clinical and histological characteristics are analogous to hereditary ataxias in humans. Linkage and genome-wide association studies on a cohort of related Old English Sheepdogs identified a region on CFA4 strongly associated with the disease phenotype. Targeted sequence capture and next generation sequencing of the region identified an A to C single nucleotide polymorphism (SNP located at position 113 in exon 1 of an autophagy gene, RAB24, that segregated with the phenotype. Genotyping of six additional breeds of dogs affected with hereditary ataxia identified the same polymorphism in affected Gordon Setters that segregated perfectly with phenotype. The other breeds tested did not have the polymorphism. Genome-wide SNP genotyping of Gordon Setters identified a 1.9 MB region with an identical haplotype to affected Old English Sheepdogs. Histopathology, immunohistochemistry and ultrastructural evaluation of the brains of affected dogs from both breeds identified dramatic Purkinje neuron loss with axonal spheroids, accumulation of autophagosomes, ubiquitin positive inclusions and a diffuse increase in cytoplasmic neuronal ubiquitin staining. These findings recapitulate the changes reported in mice with induced neuron-specific autophagy defects. Taken together, our results suggest that a defect in RAB24, a gene associated with autophagy, is highly associated with and may contribute to canine hereditary ataxia in Old English Sheepdogs and Gordon Setters. This finding suggests that detailed investigation of autophagy pathways should be undertaken in human hereditary ataxia.

  5. Transcriptional profiling of myotubes from patients with type 2 diabetes: no evidence for a primary defect in oxidative phosphorylation genes

    DEFF Research Database (Denmark)

    Frederiksen, C M; Højlund, K; Hansen, L;

    2008-01-01

    . It is unknown whether reduced mitochondrial biogenesis or other transcriptional alterations co-exist with impaired insulin responsiveness in primary human muscle cells from patients with type 2 diabetes. METHODS: Using cDNA microarray technology and global pathway analysis with the Gene Map Annotator...

  6. A Splice Defect in the EDA Gene in Dogs with an X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Phenotype.

    Science.gov (United States)

    Waluk, Dominik P; Zur, Gila; Kaufmann, Ronnie; Welle, Monika M; Jagannathan, Vidhya; Drögemüller, Cord; Müller, Eliane J; Leeb, Tosso; Galichet, Arnaud

    2016-01-01

    X-linked hypohidrotic ectodermal dysplasia (XLHED) caused by variants in the EDA gene represents the most common ectodermal dysplasia in humans. We investigated three male mixed-breed dogs with an ectodermal dysplasia phenotype characterized by marked hypotrichosis and multifocal complete alopecia, almost complete absence of sweat and sebaceous glands, and altered dentition with missing and abnormally shaped teeth. Analysis of SNP chip genotypes and whole genome sequence data from the three affected dogs revealed that the affected dogs shared the same haplotype on a large segment of the X-chromosome, including the EDA gene. Unexpectedly, the whole genome sequence data did not reveal any nonsynonymous EDA variant in the affected dogs. We therefore performed an RNA-seq experiment on skin biopsies to search for changes in the transcriptome. This analysis revealed that the EDA transcript in the affected dogs lacked 103 nucleotides encoded by exon 2. We speculate that this exon skipping is caused by a genetic variant located in one of the large introns flanking this exon, which was missed by whole genome sequencing with the illumina short read technology. The altered EDA transcript splicing most likely causes the observed ectodermal dysplasia in the affected dogs. These dogs thus offer an excellent opportunity to gain insights into the complex splicing processes required for expression of the EDA gene, and other genes with large introns. PMID:27449516

  7. A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.

    Directory of Open Access Journals (Sweden)

    Firoz Abdul Samad

    Full Text Available Congenital heart defects (CHD presented as structural defects in the heart and blood vessels during birth contribute an important cause of childhood morbidity and mortality worldwide. Many Single nucletotide polymorphisms (SNPs in different genes have been associated with various types of congenital heart defects. NKX 2-5 gene is one among them, which encodes a homeobox-containing transcription factor that plays a crucial role during the initial phases of heart formation and development. Mutations in this gene could cause different types of congenital heart defects, including Atrial septal defect (ASD, Atrial ventricular block (AVB, Tetralogy of fallot and ventricular septal defect. This highlights the importance of studying the impact of different SNPs found within this gene that might cause structural and functional modification of its encoded protein. In this study, we retrieved SNPs from the database (dbSNP, followed by identification of potentially deleterious Non-synonymous single nucleotide polymorphisms (nsSNPs and prediction of their effect on proteins by computational screening using SIFT and Polyphen. Furthermore, we have carried out molecular dynamic simulation (MDS in order to uncover the SNPs that would cause the most structural damage to the protein altering its biological function. The most important SNP that was found using our approach was rs137852685 R161P, which was predicted to cause the most damage to the structural features of the protein. Mapping nsSNPs in genes such as NKX 2-5 would provide valuable information about individuals carrying these polymorphisms, where such variations could be used as diagnostic markers.

  8. A Comprehensive In Silico Analysis on the Structural and Functional Impact of SNPs in the Congenital Heart Defects Associated with NKX2-5 Gene-A Molecular Dynamic Simulation Approach.

    Science.gov (United States)

    Abdul Samad, Firoz; Suliman, Bandar A; Basha, Syed Hussain; Manivasagam, Thamilarasan; Essa, Musthafa Mohamed

    2016-01-01

    Congenital heart defects (CHD) presented as structural defects in the heart and blood vessels during birth contribute an important cause of childhood morbidity and mortality worldwide. Many Single nucletotide polymorphisms (SNPs) in different genes have been associated with various types of congenital heart defects. NKX 2-5 gene is one among them, which encodes a homeobox-containing transcription factor that plays a crucial role during the initial phases of heart formation and development. Mutations in this gene could cause different types of congenital heart defects, including Atrial septal defect (ASD), Atrial ventricular block (AVB), Tetralogy of fallot and ventricular septal defect. This highlights the importance of studying the impact of different SNPs found within this gene that might cause structural and functional modification of its encoded protein. In this study, we retrieved SNPs from the database (dbSNP), followed by identification of potentially deleterious Non-synonymous single nucleotide polymorphisms (nsSNPs) and prediction of their effect on proteins by computational screening using SIFT and Polyphen. Furthermore, we have carried out molecular dynamic simulation (MDS) in order to uncover the SNPs that would cause the most structural damage to the protein altering its biological function. The most important SNP that was found using our approach was rs137852685 R161P, which was predicted to cause the most damage to the structural features of the protein. Mapping nsSNPs in genes such as NKX 2-5 would provide valuable information about individuals carrying these polymorphisms, where such variations could be used as diagnostic markers. PMID:27152669

  9. Growth properties and vaccine efficacy of recombinant pseudorabies virus defective in glycoprotein E and thymidine kinase genes.

    Science.gov (United States)

    Wu, Ching-Ying; Liao, Chih-Ming; Chi, Jiun-Ni; Chien, Maw-Sheng; Huang, Chienjin

    2016-07-10

    Pseudorabies virus (PRV) is an alphaherpesvirus that causes pseudorabies (PR), an economically important viral disease of pigs. Marker vaccines were widely used in PR prevention and eradication programs. The purpose of this study was to construct a novel recombinant virus with deletions at defined regions in the glycoprotein E (gE) and thymine kinase (TK) genes by homologous recombination. This study also evaluated the safety and efficacy of the virus for a live attenuated marker vaccine. No significant difference was observed in virus replication between gE gene-deleted (gE(-)), gE/TK double gene-deleted (gE(-)TK(-)), and wild-type PRV by growth curve analysis. However, gE(-)TK(-) PRV was completely attenuated in mice. To evaluate the immunogenicity of gE(-)TK(-) PRV, four 12-week-old specific-pathogen-free pigs per group were immunized intramuscularly with viral titers of 1×10(4), 1×10(5), or 1×10(6) TCID50, followed by intranasal challenge infection with virulent PRV (1×10(8) TCID50) at 3 weeks post vaccination. The gE(-)TK(-) PRV-vaccinated pigs displayed no general adverse effects after immunization and had protective immune responses after PRV challenge. Thus, gE(-)TK(-) PRV was safe and efficacious and might be a potential candidate for a live attenuated marker vaccine against PRV. PMID:27164258

  10. The use of SHP-2 gene transduced bone marrow mesenchymal stem cells to promote osteogenic differentiation and bone defect repair in rat.

    Science.gov (United States)

    Fan, Dapeng; Liu, Shen; Jiang, Shichao; Li, Zhiwei; Mo, Xiumei; Ruan, Hongjiang; Zou, Gang-Ming; Fan, Cunyi

    2016-08-01

    Bone tissue engineering is a promising approach for bone regeneration, in which growth factors play an important role. The tyrosine phosphatase Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is essential for the differentiation, proliferation and metabolism of osteoblasts. However, SHP-2 has never been systematically studied for its effect in osteogenesis. We predicted that overexpression of SHP-2 could promote bone marrow-derived mesenchymal stem cell (BMSC)osteogenic differentiation and SHP-2 transduced BMSCs could enhance new bone formation, determined using the following study groups: (1) BMSCs transduced with SHP-2 and induced with osteoblast-inducing liquid (BMSCs/SHP-2/OL); (2) BMSCs transduced with SHP-2 (BMSCs/-SHP-2); (3) BMSCs induced with osteoblast-inducing liquid (BMSCs/OL) and (4) pure BMSCs. Cells were assessed for osteogenic differentiation by quantitative real-time polymerase chain reaction analysis, western blot analysis, alkaline phosphatase activity and alizarin red S staining. For in vivo assessment, cells were combined with beta-tricalcium phosphate scaffolds and transplanted into rat calvarial defects for 8 weeks. Following euthanasia, skull samples were explanted for osteogenic evaluation, including micro-computed tomography measurement, histology and immunohistochemistry staining. SHP-2 and upregulation of its gene promoted BMSC osteogenic differentiation and therefore represents a potential new therapeutic approach to bone repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1871-1881, 2016. PMID:26999642

  11. Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

    Science.gov (United States)

    Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

    2013-08-15

    The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice. PMID:23764895

  12. Splicing Defect in Mitochondrial Seryl-tRNA Synthetase Gene Causes Progressive Spastic Paresis Instead of HUPRA Syndrome.

    Science.gov (United States)

    Linnankivi, Tarja; Neupane, Nirajan; Richter, Uwe; Isohanni, Pirjo; Tyynismaa, Henna

    2016-09-01

    Mitochondrial aminoacyl-tRNA synthetases are an important group of disease genes typically underlying either a disorder affecting an isolated tissue or a distinct syndrome. Missense mutations in the mitochondrial seryl-tRNA synthetase gene, SARS2, have been identified in HUPRA syndrome (hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis). We report here a homozygous splicing mutation in SARS2 in a patient with progressive spastic paresis. We show that the mutation leads to diminished levels of the synthetase in patient's fibroblasts. This has a destabilizing effect on the tRNASer(AGY) isoacceptor, but to a lesser degree than in HUPRA syndrome patients. tRNASer(UCN) is largely unaffected in both phenotypes. In conclusion, the level of tRNASer(AGY) instability may be a factor in determining tissue manifestation in patients with SARS2 mutations. This finding exemplifies the sensitivity of the nervous system to partially reduced aminoacylation, which is sufficient in other tissues to maintain respiratory chain function. PMID:27279129

  13. The defect

    CERN Document Server

    Kuhlmann, Franz-Viktor

    2010-01-01

    We give an introduction to the valuation theoretical phenomenon of "defect", also known as "ramification deficiency". We describe the role it plays in deep open problems in positive characteristic: local uniformization (the local form of resolution of singularities), the model theory of valued fields, the structure theory of valued function fields. We give several examples of algebraic extensions with non-trivial defect. We indicate why Artin-Schreier defect extensions play a central role and describe a way to classify them. Further, we give an overview of various results about the defect that help to tame or avoid it, in particular "stability" theorems and theorems on "henselian rationality", and show how they are applied. Finally, we include a list of open problems.

  14. Paravaginal defect

    DEFF Research Database (Denmark)

    Arenholt, Louise T S; Pedersen, Bodil Ginnerup; Glavind, Karin;

    2016-01-01

    , arcus tendineus fascia pelvis (ATFP), pubocervical fascia, and uterosacral/cardinal ligaments. Studies conclude that physical examination is inconsistent in detecting paravaginal defects. Ultrasound (US) and magnetic resonance imaging (MRI) have been used to describe patterns in the appearance...

  15. Prenatal Diagnosis of Single-Gene Defects%单基因病的产前诊断研究进展

    Institute of Scientific and Technical Information of China (English)

    严恺; 金帆

    2013-01-01

    单基因病是导致新生儿出生缺陷的主要原因之一,大多数单基因病患者预后不佳。对于有单基因病患儿出生史的家系,在先证者致病基因及突变类型明确的基础上,可通过产前诊断防止患儿的出生。目前,单基因病的产前诊断可分为植入前遗传学诊断(PGD)和妊娠期产前诊断。传统的产前诊断通过有创手术获取胎儿源性标本,准确性高,但具有一定程度的流产风险。PGD和无创产前诊断(NIPD)作为新的产前诊断方式,在一定程度上可作为传统方式的补充。综述单基因病产前诊断技术的研究进展及遗传咨询的重要意义,为临床实践产前诊断的方案制定提供一定的思路。%Single-gene defects, which has the unfavorable prognosis, is the main cause of the newborn's defect. Couples can prevent birth of child carrying the same genetic disorder with the proband. Currently, the prenatal diagnosis contains preimplantation genetic diagnosis and trimester prenatal diagnosis. Traditional invasive prenatal diagnosis acquire specimens from fetal relying on surgery. It is accurate, but with a certain risk of miscarriage. The new method of prenatal diagnosis (such as preimplantation genetic diagnosis and non-invasive prenatal diagnosis) and the traditional way are complementary to one another. In this review, we discuss the progress of prenatal diagnosis of Single-gene defects and the significance of genetic counseling in order to provide some ideas in clinical practice.

  16. Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway.

    Directory of Open Access Journals (Sweden)

    Jordi Perez-Gil

    Full Text Available A functional 2-C-methyl-D-erythritol 4-phosphate (MEP pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP by the activity of the enzymes DXP synthase (DXS and DXP reductoisomerase (DXR. Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.

  17. Multiple Defects of Cell Cycle Checkpoints in U937-ASPI3K, an U937 Cell Mutant Stably Expressing Anti-Sense ATM Gene cDNA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    (Ataxia-telangiectasia mutated gene (ATM) functions in control of cell cycle checkpoints in responding to DNA damage and protects cells from undergoing apoptosis. Knock-out within tumor cells of endogenous ATM will achieve therapeutic benefits and nable a better understanding of the decisive mechanisms of cell death or survival in response to DNA damaging agents. ) In present paper, we sought to characterize the cell cycle checkpoint profiles in U937-ASPI3K, a U937 cell mutant that was previously established with endogenous ATM knock-out phenotype. Synchronized U937-ASPI3K was exposed to 137Cs irradiation, G1, S, G2/M cell cycle checkpoint profiles were evaluated by determining cell cycle kinetics, p53/p21 protein, cyclin dependent kinase 2 (CDK2) and p34CDC2 kinase activity in response to irradiation. U937-ASPI3K exhibited multiple defects in cell cycle checkpoints as defined by failing to arrest cells upon irradiation. The accumulation of cellular p53/p21 protein and inhibition of CDK kinase was also abolished in U937-ASPI3K. It was concluded that the stable expression of anti-sense PI3K cDNA fragment completely abolished multiple cell cycle checkpoints in U937-ASPI3K, and hence U937-ASPI3K with an AT-like phenotype could serves as a valuable model system for investigating the signal transduction pathway in responding to DNA damaging-based cancer therapy.

  18. Vacuolar invertase gene silencing in potato (Solanum tuberosum L.) improves processing quality by decreasing the frequency of sugar-end defects

    Science.gov (United States)

    Sugar-end defect is a tuber quality disorder that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one end of the tuber. Reducing sugars produced by invertase form da...

  19. Defying birth defects through diet?

    OpenAIRE

    Crider, Krista S.; Lynn B. Bailey

    2011-01-01

    The risk of certain birth defects can be modified by maternal diet. A high-fat maternal mouse diet has recently been reported to substantially increase the penetrance of birth defects known to be associated with a deficiency of transcription factor Cited2 as well as induce cleft palate. These effects were associated with a more than twofold reduction in embryonic expression of Pitx2c. This investigation suggests the need to further explore this provocative gene-diet interaction in human studies.

  20. Comparative Immunization in BALB/c Mice with Recombinant Replication-Defective Adenovirus Vector and DNA Plasmid Expressing a SARS-CoV Nucleocapsid Protein Gene

    Institute of Scientific and Technical Information of China (English)

    Chunling Ma; Kun Yao; Feng Zhou; Minsheng Zhu

    2006-01-01

    In order to investigate immunogenicity in the induction of humoral and cellular immune responses, severe acute respiratory syndrome associated coronavirus (SARS-CoV)-N gene recombinant replication-defective adenoviral vector, rAd-N, was generated and immunized BALB/c mice in a pcDNA3.1-N prime-rAd-N boost regimen. After humoral and cellular immune response detection, different levels of SARS-CoV N protein specific antibodies and interferon-γ (IFN-γ) secretion are shown compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen. There is a significant difference between heterogeneous and homologous vaccinations. The heterogeneous combinations were all higher than those of the homologous combinations in the induction of anti-N antibody response. Among the three heterogeneous combinations, pcDNA3.1-N/pcDNA3.1-N/pcDNA3.1-N/rAd-N induced the strongest antibody response. In the induction of IFN-γ production, the homologous combination of rAd-N/rAd-N/rAd-N/rAd- N was significantly stronger than that of pcDNA3.1-N/pcDNA3. 1-N/pcDNA3.1-N/pcDNA3.1-N, but was relatively weaker than the heterogeneous combination of pcDAN3.1-N/pcDAN3.1-N/pcDAN3.1-N/rAd-N. This combination was a most efficient immunization regimen in induction of SARS-CoV-N-specific (IFN-γ) secretion just as the antibody response. These results suggest that DNA immunization followed by recombinant adenovirus boosting could be used as a potential SARS-CoV vaccine.

  1. Hyperosmia, ectrodactyly, mild intellectual disability, and other defects in a male patient with an X-linked partial microduplication and overexpression of the KAL1 gene.

    Science.gov (United States)

    Sowińska-Seidler, Anna; Piwecka, Monika; Olech, Ewelina; Socha, Magdalena; Latos-Bieleńska, Anna; Jamsheer, Aleksander

    2015-05-01

    Loss-of-function mutations of the KAL1 gene are a known cause of Kallmann syndrome, a disorder characterized by the coexistence of hypogonadotropic hypogonadism and anosmia/hiposmia. On the other hand, neither complete nor partial duplications of KAL1 have been reported in the literature; thus, clinical symptoms associated with such alterations remain unknown. Ectrodactyly is a clinically and genetically heterogeneous abnormality presenting with hypoplasia of the central rays of the extremity, which, in around 68% of cases, has unknown underlying molecular defect. In this paper, we report on a sporadic male patient manifesting hyperosmia and ectrodactyly accompanied by additional symptoms involving mild intellectual disability, unilateral hearing loss, genital anomalies, stocky build, and facial dysmorphism. Using a combination of high-resolution array comparative genomic hybridization (array CGH) and breakpoint analysis, we detected a hemizygous tandem duplication of 110,967 bp on Xp22.31, encompassing the promoter region and the first two exons of KAL1. In order to confirm pathogenicity of the duplication, we tested the level of KAL1 transcript in blood lymphocytes, showing 79 times higher expression in the proband compared to controls. We, therefore, hypothesize that olfactory hypersensitivity in our proband directly results from KAL1 overproduction. Additionally, a literature review allowed us to conclude that KAL1 protein at high levels may interfere with FGFR1 signaling activity, most probably indirectly giving rise to ectrodactyly, intellectual disability, and genital anomalies. Noteworthy, those symptoms overlap with Hartsfield syndrome caused by FGFR1 loss-of-function mutations. To conclude, our paper highlights the role of KAL1 in embryogenesis and provides data on the contribution of KAL1 overexpression to human pathology. PMID:25339597

  2. Al-Aqeel Sewairi Syndrome, a new autosomal recessive disorder with multicentric osteolysis, nodulosis and arthropathy. The first genetic defect of matrix metalloproteinase 2 gene

    International Nuclear Information System (INIS)

    We report a distinctive autosomal recessive multicentric osteolysis in Saudi Arabian families with distal arthropathy of the metacarpal, metatarsal and interphalangeal joints, with ultimate progression to the proximal joints with decreased range of movements and deformities with ankylosis and generalized osteopenia. In addition, they had large, painful to touch palmar and plantar pads. Hirsutism and mild dysmorphic facial features including proptosis, a narrow nasal bridge, bulbous nose and micrognathia. Using a genome-wide search for microsatellite markers from 11 members of the family from the Armed Forces Hospital and King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, localized the disease gene to chromosome 16q12-21. Haplotype analysis with additional markers narrowed the critical region to 1.2cM and identified the matrix metalloproteinase 2 (MMP-2), (gelatinase A, collagenase type IV, EC 3.4, 24,24) gene as a disease candidate at Mount Sinai School of Medicine, New York, United States of America in April 2000. Some affected individuals were homoallelic for a nonsense mutation (TCA>TAA) in codon 244 of exon 5, predicting the replacement of a tyrosine residue by a stop codon in the first fibronectin type II domain (Y244X). Other affected members had a missense mutation in exon 2 arginine 101-histidine (R101H) leading to no MMP-2 enzyme activity in serum or fibroblast or both of affected individuals. In other affected members, a non-pathogenic homoallelic GT transversion resulted in the substitution of an aspartate with a tyrosine residue in codon 210 of exon 4 (D210Y). The MMP-2-null mouse has no developmental defects, but are small, which may reflect genetic redundancy. The discovery that deficiency of this well-characterized gelatinase/collagenase results in an inherited form of an osteolytic and arthritic disorder provides an invaluable insights for the understanding of osteolysis and arthritis and is the first genetic

  3. Vacuolar Invertase Gene Silencing in Potato (Solanum tuberosum L.) Improves Processing Quality by Decreasing the Frequency of Sugar-End Defects

    OpenAIRE

    Xiaobiao Zhu; Craig Richael; Patrick Chamberlain; Busse, James S; Alvin J. Bussan; Jiming Jiang; Paul C Bethke

    2014-01-01

    Sugar-end defect is a tuber quality disorder and persistent problem for the French fry processing industry that causes unacceptable darkening of one end of French fries. This defect appears when environmental stress during tuber growth increases post-harvest vacuolar acid invertase activity at one end of the tuber. Reducing sugars produced by invertase form dark-colored Maillard reaction products during frying. Acrylamide is another Maillard reaction product formed from reducing sugars and ac...

  4. Isolation and Characterization of New Alleles of the Cyclin-Dependent Kinase Gene CDC28 with Cyclin-Specific Functional and Biochemical Defects

    OpenAIRE

    Levine, Kristi; Oehlen, L. J. W. M.; Cross, Frederick R.

    1998-01-01

    The G1 cyclin Cln2 negatively regulates the mating-factor pathway. In a genetic screen to identify factors required for this regulation, we identified an allele of CDC28 (cdc28-csr1) that blocked this function of Cln2. Cln2 immunoprecipitated from cdc28-csr1 cells was completely defective in histone H1 kinase activity, due to defects in Cdc28 binding and activation by Cln2. In contrast, Clb2-associated H1 kinase and Cdc28 binding was normal in immunoprecipitates from these cells. cdc28-csr1 w...

  5. X-linked recessive genetic defects - how girls are affected (image)

    Science.gov (United States)

    ... may get the defective gene either from her mother's defective X, or, if her father has the disorder, from her father. In either case, the girl will be a carrier and will probably pass the defect to her ...

  6. Ventricular septal defect (image)

    Science.gov (United States)

    Ventricular septal defect is a congenital defect of the heart, that occurs as an abnormal opening in ... wall that separates the right and left ventricles. Ventricular septal defect may also be associated with other ...

  7. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  8. Interaction between maternal 5,10-methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene variants to increase the risk of fetal neural tube defects in a Shanxi Han population

    Institute of Scientific and Technical Information of China (English)

    LIU Zhi-zhen; ZHANG Jun-tao; LIU Dan; HAO Yu-hui; CHANG Bing-mei; XIE Jun; LI Pei-zhen

    2013-01-01

    Background The 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are attractive candidates for screening for risk of neural tube defects (NTDs).The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China.Methods Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group.All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms.SPSS 11.5 software package was used for all analyses.Results There was a significant difference for MTHFR genotype distribution for one site (C677T) between the case and control groups.The T allele frequencies were significantly higher in the case group than in the control group (55.9% vs.35.3%,P <0.05).A lack of association was observed for the MS A2756G polymorphism.There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype.Conclusion Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.

  9. The relationship between folate metabolism Related Gene and Birth Defects, Poor Pregnancy%叶酸代谢基因与出生缺陷和不良妊娠的关系

    Institute of Scientific and Technical Information of China (English)

    刘英华; 陈瑛

    2012-01-01

    More and more study shown that folate had important role in the birth defects such as congenital heart disease and neural tube defects, adverse pregnancy such as premature birth and abortion. However, promotion " folic acid fortification" will artificially lead to future population dependent on a large number of vitamin, lead to the overall gene composition changed, the crowd will become very fragile to a fatal disease, folate level in whose is lower than that in normal persons. Maternal folate deficiency may result in general impairment of fetal growth, which is reflected in low birth weight. Such women also have a high incidence of abortion, ab-ruptio placentae and fetal malformation. Folate supplemented in pregnant women with the appropriate dose can reduce the risk of diseases such as birth defects and adverse pregnancy. In this article, we discussed the relationship between polymorphisms of enzyme genes involving folate metabolism and risk of birth defects such as congenital heart disease and neural tube defects, adverse pregnancy such as premature birth and abortion.%叶酸在先天性心脏病、神经管畸形等出生缺陷和早产、流产等不良妊娠中的作用越来越受到关注.然而,研究表明推广“叶酸强化”将人为地导致未来的人口对于大量的维生素产生依赖性,导致人口整体的基因组发生变化,这种人群对于某种致命的疾病将变得十分脆弱,患者体内的叶酸水平低于正常个体,产妇叶酸缺乏会因产生低出生体重的胎儿而损害胎儿的生长,另外还有流产、胎儿畸形和胎盘早剥等高发病率的风险.孕妇在妊娠前和妊娠期补充适量的叶酸可降低出生缺陷、不良妊娠等疾病的发生概率.因此,本研究就近几年国内外关于叶酸代谢相关酶基因多态性和先天性心脏病、神经管畸形等出生缺陷和早产、流产等不良妊娠关系进行简要综述.

  10. Advances in the Relationship between Polymorphisms of Genes Involved in the Folate Metabolic Pathway and Birth Defects%叶酸代谢基因多态性与出生缺陷的关系

    Institute of Scientific and Technical Information of China (English)

    罗丽; 陈岳明; 王贤军

    2015-01-01

    With birth mortality decreasing significantly ,birth defects have become more serious in China. Increasing evidences supported the polymorphisms of genes involved in the folate metabolic pathway impact the occurrence of birth defects. MTHFR 677C>T polymorphism impacting the occurrence of neural tube defects had reached a consistent conclusion. However,the relationship between MTHFR 677C>T, MTHFR 1298A>C and cleft lip/palate,congenital heart disease,Down′s syndrome is still controversial. Researches seldom took further study on the correlation between MTR 2756A>G,MTRR 66A>G,RFC-1 80A>G polymorphism and birth defects. In this summary,we outlined the origination of folate,metabolic pathway and the association between the polymorphisms of genes involved in the pathway and birth defects.%随着我国新生儿出生死亡率明显降低,出生缺陷问题日益突出。在降低新生儿出生缺陷发生率的众多研究中,发现叶酸吸收代谢途径基因多态性与出生缺陷发生存在明显相关性。亚甲基四氢叶酸还原酶(MTHFR)677C>T多态性与神经管缺损发生明显相关已取得较为一致的结论。但MTHFR 677C>T、MTHFR 1298A>C在唇裂/腭裂、先天性心脏病、唐氏综合征的发生中所起的作用结论尚不统一,并且较少涉及叶酸代谢通路中甲硫氨酸合成酶(MTR)2756A>G、甲硫氨酸合成还原酶(MTRR)66A>G、还原型叶酸载体-1(RFC-1)80A>G多态性与出生缺陷的研究。就叶酸来源、吸收代谢途径及代谢途径关键基因多态性与出生缺陷的相关性进行综述。

  11. 肌醇代谢关键基因与神经管畸形关系的研究进展%Advances in the relationship between key genes in inositol metabolism and neural tube defects

    Institute of Scientific and Technical Information of China (English)

    石英飞

    2015-01-01

    Neural tube defect (NTD) is a complex and serious birth defect in the central nervous system.The etiology of NTD is multifactorial,involving the combined action of both genetic and environmental factors.Maternal nutrition is a significant environmental factor in NTD etiology,including vitamin B,folic acid,choline,and so on.Inositol,a substance of vitamin B,is closely related to embryonic development and NTD.Studies have found out that inositol supplement can prevent folic acid-resistant NTD and the key genes in its metabolic pathways play an important role in NTD occurrence.Therefore,this article reviews the inositol metabolic pathways and the relationship between its key genes and NTD,providing references for the depth study of NTD pathogenesis and prevention.%神经管畸形(neural tube defect,NTD)是一种复杂的、严重的中枢神经系统出生缺陷,由遗传与环境因素共同影响.母体营养物质是NTD病因中一个重要的环境因素,包括维生素B族物质、叶酸及胆碱等.肌醇作为一种维生素B族物质,与胚胎发育及NTD发生密切相关.研究发现,肌醇补充可预防叶酸抵抗型NTD,且其代谢通路关键基因在NTD发生过程中起着重要的作用.该文就肌醇代谢通路及其关键基因与NTD发生的关系进行综述,以期为NTD发病机制的深入研究及防治提供参考.

  12. Mating-type suppression of the DNA-repair defect of the yeast rad6 delta mutation requires the activity of genes in the RAD52 epistasis group.

    Science.gov (United States)

    Yan, Y X; Schiestl, R H; Prakash, L

    1995-06-01

    The RAD6 gene of Saccharomyces cerevisiae is required for post-replication repair of UV-damaged DNA, UV mutagenesis, and sporulation. Here, we show that the radiation sensitivity of a MATa rad6 delta strain can be suppressed by the MAT alpha 2 gene carried on a multicopy plasmid. The a1-alpha 2 suppression is specific to the RAD6 pathway, as mutations in genes required for nucleotide excision repair or for recombinational repair do not show such mating-type suppression. The a1-alpha 2 suppression of the rad6 delta mutation requires the activity of the RAD52 group of genes, suggesting that suppression occurs by channelling of post-replication gaps present in the rad6 delta mutant into the RAD52 recombinational repair pathway. The a1-alpha 2 repressor could mediate this suppression via an enhancement in the expression, or the activity, of recombination genes.

  13. Isolation and characterization of new alleles of the cyclin-dependent kinase gene CDC28 with cyclin-specific functional and biochemical defects.

    Science.gov (United States)

    Levine, K; Oehlen, L J; Cross, F R

    1998-01-01

    The G1 cyclin Cln2 negatively regulates the mating-factor pathway. In a genetic screen to identify factors required for this regulation, we identified an allele of CDC28 (cdc28-csr1) that blocked this function of Cln2. Cln2 immunoprecipitated from cdc28-csr1 cells was completely defective in histone H1 kinase activity, due to defects in Cdc28 binding and activation by Cln2. In contrast, Clb2-associated H1 kinase and Cdc28 binding was normal in immunoprecipitates from these cells. cdc28-csr1 was significantly deficient in other aspects of genetic interaction with Cln2. The cdc28-csr1 mutation was determined to be Q188P, in the T loop distal to most of the probable Cdk-cyclin interaction regions. We performed random mutagenesis of CDC28 to identify additional alleles incapable of causing CLN2-dependent mating-factor resistance but capable of complementing cdc28 temperature-sensitive and null alleles. Two such mutants had highly defective Cln2-associated kinase, but, surprisingly, two other mutants had levels of Cln2-associated kinase near to wild-type levels. We performed a complementary screen for CDC28 mutants that could cause efficient Cln2-dependent mating-factor resistance but not complement a cdc28 null allele. Most such mutants were found to alter residues essential for kinase activity; the proteins had little or no associated kinase activity in bulk or in association with Cln2. Several of these mutants also functioned in another assay for CLN2-dependent function not involving the mating-factor pathway, complementing the temperature sensitivity of a cln1 cln3 cdc28-csr1 strain. These results could indicate that Cln2-Cdc28 kinase activity is not directly relevant to some CLN2-mediated functions. Mutants of this sort should be useful in differentiating the function of Cdc28 complexed with different cyclin regulatory subunits. PMID:9418876

  14. Par-3 partitioning defective 3 homolog (C. elegans and androgen-induced prostate proliferative shutoff associated protein genes are mutationally inactivated in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Ivanov Igor

    2009-09-01

    Full Text Available Abstract Background Gene identification by nonsense-mediated mRNA decay inhibition (GINI has proven its usefulness in identifying mutant genes in cancer cell lines. An increase in transcription in response to NMD inhibition of a subset of genes is a major cause of false positives when genes are selected for sequencing analysis. To distinguish between mRNA accumulations caused by stress response-induced transcription and nonsense-containing mRNA stabilizations is a challenge in identifying mutant genes using GINI. Methods To identify potential tumor-suppressor genes mutated in prostate cancer cell lines, we applied a version of GINI that involves inhibition of NMD in two steps. In the first step, NMD is inhibited in duplicate tissue-culture plates. During this step, both the substrate for NMD and stress-response mRNA transcripts are accumulated in cells. In the second step, transcription is inhibited in both plates and NMD is inhibited in one plate and released in the second plate. Microarray analysis of gene-expression profiles in both plates after the second step detects only the differences in mRNA degradation but not in mRNA accumulation. Results Analyzing gene expression profile alterations in 22RV1 and LNCaP prostate cancer cells following NMD inhibition we selected candidates for sequencing analysis in both cell lines. Sequencing identified inactivating mutations in both alleles of the PARD3 and AS3 genes in the LNCaP and 22RV1 cells, respectively. Introduction of a wild-type PARD3 cDNA into the LNCaP cells resulted in a higher proliferation rate in tissue culture, a higher adhesion of LNCaP cells to the components of extracellular matrix and impaired the growth of the LNCaP cells in soft agar and in a three-dimensional cell-culture. Conclusion The mutational inactivation in a prostate cancer cell line of the PARD3 gene involved in asymmetric cell division and maintenance of cell-polarity suggests that the loss of cell-polarity contributes

  15. Altered DNA methylation patterns of the H19 differentially methylated region and the DAZL gene promoter are associated with defective human sperm.

    Directory of Open Access Journals (Sweden)

    Bo Li

    Full Text Available DNA methylation disturbance is associated with defective human sperm. However, oligozoospermia (OZ and asthenozoospermia (AZ usually present together, and the relationship between the single-phenotype defects in human sperm and DNA methylation is poorly understood. In this study, 20 infertile OZ patients and 20 infertile AZ patients were compared with 20 fertile normozoospermic men. Bisulfate-specific PCR was used to analyze DNA methylation of the H19-DMR and the DAZL promoter in these subjects. A similar DNA methylation pattern of the H19-DMR was detected in AZ and NZ(control, with only complete methylation and mild hypomethylation(0.05. However, the methylation pattern of severe hypomethylation (>50% unmethylated CpGs and complete unmethylation was only detected in 5 OZ patients, and the occurrence of these two methylation patterns was 8.54±10.86% and 9±6.06%, respectively. Loss of DNA methylation of the H19-DMR in the OZ patients was found to mainly occur in CTCF-binding site 6, with occurrence of 18.15±14.71%, which was much higher than that in patients with NZ (0.84±2.05% and AZ (0.58±1.77% (P20% methylated clones in the DAZL promoter only in infertile patients, there was no significant difference between the AZ and OZ patients in the proportion of moderately-to-severely hypermethylated clones (p>0.05. In all cases, global sperm genome methylation analyses, using LINE1 transposon as the indicator, showed that dysregulation of DNA methylation is specifically associated with the H19-DMR and DAZL promoter. Therefore, abnormal DNA methylation status of H19-DMR, especially at the CTCF-binding site 6, is closely associated with OZ. Abnormal DNA methylation of the DAZL promoter might represent an epigenetic marker of male infertility.

  16. Deletion of the topoisomerase III gene in the hyperthermophilic archaeon Sulfolobus islandicus results in slow growth and defects in cell cycle control

    DEFF Research Database (Denmark)

    Li, Xiyang; Guo, Li; Deng, Ling;

    2011-01-01

    Topoisomerase III (topo III), a type IA topoisomerase, is widespread in hyperthermophilic archaea. In order to interrogate the in vivo role of archaeal topo III, we constructed and characterized a topo III gene deletion mutant of Sulfolobus islandicus. The mutant was viable but grew more slowly t...

  17. BMP2基因修饰犬脂肪源性基质细胞修复自体大段骨缺损%Repairing canine segmental bone defects using BMP2 gene modified adipose-derived stromal cells

    Institute of Scientific and Technical Information of China (English)

    李慧武; 戴尅戎; 汤亭亭; 张晓玲; 唐坚; 孙晓江; 张双燕; 楼觉人

    2008-01-01

    Objective To evaluate osteogenetic effectiveness of porous β-tricalcium phosphate(β-TCP) ceramic mixed with human bone morphogenetic protein2 gene(Adv-hBMP2)modified adipose derived stromal cells (ADSCs) in the repair of critical-sized bone defects..Methods The ADSCs taken from the back of beagle dogs were modified by the BMP2 gene.The expression and bone-induction ability of BMP2 was identified by ELISA and ectopic bone formation in nude mice.The cells were applied to a β-tricalcium phosphate (TGP)carrier and implanted into ulnar bone defects in the canine model.18 ulnar bone defects were divided into three groups randomly and filled with granular TCP alone,granular TCP and ADSCs,or TCP and ADSCs transduced with Adv-hBMP2 respectively.All dogs were followed clinically and roentgenographically for 16 weeks and then sacrificed.Results ELISA and ectopic bone formation in nude mice showed the recombinant ADSCs could express BMP2 highly and stably.No bone defects healed after implanting granular TCP alone or granular TCP and ADSCs.In the TCP and ADSCs transduced with AdvhBMP2 group,two defects healed,four partly healed.Histological examination showed woven bone at the both end of the cortices but entirelv fibrous tissue in the middle in which defects filled with TCP alone or TCP and ADSCs.Defects filled with TCP and transduced ADSCs showed substatial new bone formation.Histomorphometry showed TCP combined with ADSCs did not significantly increase new bone area compared with TCP alone.TCP and recombinant ADSCs produced a significant increase in newly formed bone area.Conclusion ADSCs tansduced with BMP2 gene in a TCP carrier can enhance bone regeneratmn to repair the critically-sized bone defect.%目的 评价BMP2基因修饰的犬脂肪源性基质细胞(ADSCs)与β-磷酸三钙(β-TCP)复合修复自体大段骨缺损的疗效.方法 从比格犬背部脂肪组织中提取基质细胞,转染腺病毒介导的人BMP2基因(Adv-hBMP2),通过ELISA和裸鼠体

  18. Atopic dermatitis : Aspects of defence defects

    OpenAIRE

    Hagströmer, Lena

    2009-01-01

    Atopic dermatitis (AD) is an inflammatory skin disease, typically with a chronic relapsing course and a defective skin barrier function. Recently, mutations of the skin barrier gene encoding filaggrin have been reported in a portion of the patients. In this thesis some aspects of defence defects in AD were studied. In paper I, the risk of developing any cancer was increased by 13%. Excess risks were observed for cancers of the esophagus, pancreas, brain, and lung and for...

  19. [SOX2 defect and anophthalmia and microphthalmia].

    Science.gov (United States)

    Ye, Fu-xiang; Fan, Xian-qun

    2012-11-01

    As a severe congenital developmental disorder, anophthalmia and microphthalmia are usually accompanied with vision impairment and hypoevolutism of the orbit in the affected side. Many genes are involved in anophthalmia and microphthalmia, in which, SOX2 is an important one. The defect of SOX2 causes multiple system disorders, including anophthalmia and microphthalmia. We describe the relationship between the SOX2 defect and anophthalmia/microphthalmia, in order to offer some proposals for the differential diagnosis, treatment and research of anophthalmia and microphthalmia.

  20. Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes developmental delay, cardiovascular defects, and early embryonic lethality.

    Directory of Open Access Journals (Sweden)

    Paula Dietrich

    Full Text Available Familial Dysautonomia (FD is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function.

  1. Hyperosmia, ectrodactyly, mild intellectual disability, and other defects in a male patient with an X-linked partial microduplication and overexpression of the KAL1 gene

    OpenAIRE

    Sowińska-Seidler, Anna; Piwecka, Monika; Olech, Ewelina; Socha, Magdalena; Latos-Bieleńska, Anna; Jamsheer, Aleksander

    2014-01-01

    Loss-of-function mutations of the KAL1 gene are a known cause of Kallmann syndrome, a disorder characterized by the coexistence of hypogonadotropic hypogonadism and anosmia/hiposmia. On the other hand, neither complete nor partial duplications of KAL1 have been reported in the literature; thus, clinical symptoms associated with such alterations remain unknown. Ectrodactyly is a clinically and genetically heterogeneous abnormality presenting with hypoplasia of the central rays of the extremity...

  2. Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn’s Disease Patients

    Science.gov (United States)

    Choteau, Laura; Vasseur, Francis; Lepretre, Frederic; Figeac, Martin; Gower-Rousseau, Corine; Dubuquoy, Laurent; Poulain, Daniel; Colombel, Jean-Frederic; Sendid, Boualem; Jawhara, Samir

    2016-01-01

    Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn’s disease and this deficiency is frequently associated with a severe Crohn’s disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn’s disease phenotype in 69 Crohn’s disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin–mannose-associated serine protease (MBL-MASP) functional activity in Crohn’s disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn’s disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn’s disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants. PMID:27404661

  3. Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.

    Science.gov (United States)

    Choteau, Laura; Vasseur, Francis; Lepretre, Frederic; Figeac, Martin; Gower-Rousseau, Corine; Dubuquoy, Laurent; Poulain, Daniel; Colombel, Jean-Frederic; Sendid, Boualem; Jawhara, Samir

    2016-01-01

    Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants. PMID:27404661

  4. Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.

    Science.gov (United States)

    Choteau, Laura; Vasseur, Francis; Lepretre, Frederic; Figeac, Martin; Gower-Rousseau, Corine; Dubuquoy, Laurent; Poulain, Daniel; Colombel, Jean-Frederic; Sendid, Boualem; Jawhara, Samir

    2016-01-01

    Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

  5. Identification of four genes involved in suppression of the pre-mRNA splicing defect in the sng1-1/rhp6- mutant of fission yeast

    Indian Academy of Sciences (India)

    Alpana Naresh; Jagmohan Singh

    2000-01-01

    Apart from the global regulators of silencing in the fission yeast Schizosaccharomyces pombe, namely swi6, clr1, clr2, clr3, clr4 and rik1, the DNA repair gene rhp6 plays a unique role in mating-type silencing. Recently, we showed that sng1-1, a mutation in the 5′ splice junction of the second intron of the rhp6 gene, leads to derepression of both the silent loci mat2 and mat3 in switching background. To address the mechanism of rhp6 in silencing, we have isolated several extragenic suppressors of the sng1-1/rhp6- mutation. These suppressors fall into four complementation groups and are referred to as suppressor of rhp6: sur1, sur2, sur3 and sur4. Interestingly, reverse transcriptase polymerase chain reaction analysis of the rhp6 transcript shows that in contrast to about > 50% level of unspliced rhp6 pre-mRNA in the sng1-1/rhp6- mutant, there is a restoration of normal splicing to varying degrees in the suppressors. The sur2 gene belongs to the AAA-ATPase family of proteins, with maximum homology to the SIN1-associated protein SAP1 of Saccharomyces cerevisiae. We propose that sur2, along with sur1, sur3 and sur4, may play an as yet uncharacterized role in pre-mRNA splicing.

  6. Positive selection of mutants with cell envelope defects of a Salmonella typhimurium strain hypersensitive to the products of genes hisF and hisH. [uv radiation

    Energy Technology Data Exchange (ETDEWEB)

    Anton, D.N.

    1979-03-01

    Strain SB564 and its derivative DA78 are hypersensitive to the inhibitory action of the proteins coded for by genes hisF and hisH on cell division. Transduction of hisO1242, a regulatory mutation that elicits a very high level of expression of the histidine operon, into these strains resulted in the production of long filamentous cells carrying large balloons and in growth failure. Forty-one hisO1242 derivatives that escaped inhibition were isolated. These strains showed a large variety of alterations, many of which were related to the cell envelope. The more-frequent alterations included: changes in cell shape, increased sensitivity to one or more of several drugs (deoxycholate, cycloserine, penicillin, novobiocin, acridine orange), increased autolytic activity in alkaline buffer, anomalous fermentation of maltose on eosin--methylene blue plates, and temperature-conditional cell division. The alterations are produced, in some of the strains, by pleiotropic mutations in gene envB. Strains affected in divC, divD, and rodA loci have also been identified. Genetic analaysis has shown that several strains carry more than one envelope mutation. It is assumed that envelope mutations are positively selected because they somehow alleviate the particularly severe inhibition of cell division caused, in strains SB564 and DA78, by the excessive synthesis of hisF and hisH gene products.

  7. Positive selection of mutants with cell envelope defects of a Salmonella typhimurium strain hypersensitive to the products of genes hisF and hisH

    International Nuclear Information System (INIS)

    Strain SB564 and its derivative DA78 are hypersensitive to the inhibitory action of the proteins coded for by genes hisF and hisH on cell division. Transduction of hisO1242, a regulatory mutation that elicits a very high level of expression of the histidine operon, into these strains resulted in the production of long filamentous cells carrying large balloons and in growth failure. Forty-one hisO1242 derivatives that escaped inhibition were isolated. These strains showed a large variety of alterations, many of which were related to the cell envelope. The more-frequent alterations included: changes in cell shape, increased sensitivity to one or more of several drugs (deoxycholate, cycloserine, penicillin, novobiocin, acridine orange), increased autolytic activity in alkaline buffer, anomalous fermentation of maltose on eosin--methylene blue plates, and temperature-conditional cell division. The alterations are produced, in some of the strains, by pleiotropic mutations in gene envB. Strains affected in divC, divD, and rodA loci have also been identified. Genetic analaysis has shown that several strains carry more than one envelope mutation. It is assumed that envelope mutations are positively selected because they somehow alleviate the particularly severe inhibition of cell division caused, in strains SB564 and DA78, by the excessive synthesis of hisF and hisH gene products

  8. Defect production in ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States); Kinoshita, C. [Kyushu Univ. (Japan)

    1997-08-01

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AIN and Si{sub 3}N{sub 4}), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed.

  9. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  10. Chorioallantoic Fusion Defects and Embryonic Lethality Resulting from Disruption of Zfp36L1, a Gene Encoding a CCCH Tandem Zinc Finger Protein of the Tristetraprolin Family

    OpenAIRE

    Stumpo, Deborah J.; Byrd, Noah A.; Phillips, Ruth S.; Ghosh, Sanjukta; Maronpot, Robert R.; Castranio, Trisha; Meyers, Erik N.; Mishina, Yuji; Blackshear, Perry J.

    2004-01-01

    The mouse gene Zfp36L1 encodes zinc finger protein 36-like 1 (Zfp36L1), a member of the tristetraprolin (TTP) family of tandem CCCH finger proteins. TTP can bind to AU-rich elements within the 3′-untranslated regions of the mRNAs encoding tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to accelerated mRNA degradation. TTP knockout mice exhibit an inflammatory phenotype that is largely due to increased TNF secretion. Zfp36L1 has activities sim...

  11. TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

    Directory of Open Access Journals (Sweden)

    Lies Vanden Broeck

    2013-01-01

    Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

  12. Profiling of the toxicity mechanisms of coated and uncoated silver nanoparticles to yeast Saccharomyces cerevisiae BY4741 using a set of its 9 single-gene deletion mutants defective in oxidative stress response, cell wall or membrane integrity and endocytosis.

    Science.gov (United States)

    Käosaar, Sandra; Kahru, Anne; Mantecca, Paride; Kasemets, Kaja

    2016-09-01

    The widespread use of nanosilver in various antibacterial, antifungal, and antiviral products warrants the studies of the toxicity pathways of nanosilver-enabled materials toward microbes and viruses. We profiled the toxicity mechanisms of uncoated, casein-coated, and polyvinylpyrrolidone-coated silver nanoparticles (AgNPs) using Saccharomyces cerevisiae wild-type (wt) and its 9 single-gene deletion mutants defective in oxidative stress (OS) defense, cell wall/membrane integrity, and endocytosis. The 48-h growth inhibition assay in organic-rich growth medium and 24-h cell viability assay in deionized (DI) water were applied whereas AgNO3, H2O2, and SDS served as positive controls. Both coated AgNPs (primary size 8-12nm) were significantly more toxic than the uncoated (~85nm) AgNPs. All studied AgNPs were ~30 times more toxic if exposed to yeast cells in DI water than in the rich growth medium: the IC50 based on nominal concentration of AgNPs in the growth inhibition test ranged from 77 to 576mg Ag/L and in the cell viability test from 2.7 to 18.7mg Ag/L, respectively. Confocal microscopy showed that wt but not endocytosis mutant (end3Δ) internalized AgNPs. Comparison of toxicity patterns of wt and mutant strains defective in OS defense and membrane integrity revealed that the toxicity of the studied AgNPs to S. cerevisiae was not caused by the OS or cell wall/membrane permeabilization. PMID:27260961

  13. Describing codimension two defects

    CERN Document Server

    Balasubramanian, Aswin

    2014-01-01

    Codimension two defects of the $(0,2)$ six dimensional theory $\\mathscr{X}[\\mathfrak{g}]$ have played an important role in the understanding of dualities for certain $\\mathcal{N}=2$ SCFTs in four dimensions. These defects are typically understood by their behaviour under various dimensional reduction schemes. In their various guises, the defects admit partial descriptions in terms of singularities of Hitchin systems, Nahm boundary conditions or Toda operators. Here, a uniform dictionary between these descriptions is given for a large class of such defects in $\\mathscr{X}[\\mathfrak{g}], \\mathfrak{g} \\in A,D,E$.

  14. Defects in semiconductors

    CERN Document Server

    Romano, Lucia; Jagadish, Chennupati

    2015-01-01

    This volume, number 91 in the Semiconductor and Semimetals series, focuses on defects in semiconductors. Defects in semiconductors help to explain several phenomena, from diffusion to getter, and to draw theories on materials' behavior in response to electrical or mechanical fields. The volume includes chapters focusing specifically on electron and proton irradiation of silicon, point defects in zinc oxide and gallium nitride, ion implantation defects and shallow junctions in silicon and germanium, and much more. It will help support students and scientists in their experimental and theoret

  15. Imaging defects and dopants

    Directory of Open Access Journals (Sweden)

    H.Philipp Ebert

    2003-06-01

    With the invention of the transistor, a revolution in the development of semiconductor-based electronic devices began. However, even in the very early stages, the importance of defects and dopant atoms became obvious. In fact, if one incorporates the right defects and dopant atoms into semiconductor materials, one can tune their electrical properties such that optimal device characteristics are achieved. Unfortunately, counteractive defects are often also formed unintentionally during semiconductor processing, leading to unfavorable electronic properties. Considerable research efforts have, therefore, focused on understanding the nanoscale physics that governs the formation of point defects, the incorporation behavior of impurities, and their respective electronic properties.

  16. Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene.

    Directory of Open Access Journals (Sweden)

    Simon Maguire

    Full Text Available Homozygosity for Slc25a21(tm1a(KOMPWtsi results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMPWtsi despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMPWtsi and Slc25a21(tm1d(KOMPWtsi alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMPWtsi mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMPWtsi mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms.

  17. Co-expression of Erns and E2 genes of classical swine fever virus by replication-defective recombinant adenovirus completely protects pigs against virulent challenge with classical swine fever virus.

    Science.gov (United States)

    Sun, Yongke; Yang, Yuai; Zheng, Huanli; Xi, Dongmei; Lin, Mingxing; Zhang, Xiaomin; Yang, Linfu; Yan, Yulin; Chu, Xiaohui; Bi, Baoliang

    2013-04-01

    The objective of this study was to construct a recombinant adenovirus for future CSFV vaccines used in the pig industry for the reduction of losses involved in CSF outbreaks. The Erns and E2 genes of classical swine fever virus (CSFV), which encode the two main protective glycoproteins from the "Shimen" strain of CSFV, were combined and inserted into the replication-defective human adenovirus type-5 and named the rAd-Erns-E2. Nine pigs were randomly assigned to three treatment groups (three pigs in each group) including the rAd-Erns-E2, hAd-CMV control and DMEM control. Intramuscular vaccination with 2×10(6) TCID(50) of the rAd-Erns-E2 was administered two times with an interval of 21 days. At 42 days post inoculation, pigs in all groups were challenged with a lethal dose of 1×10(3) TCID(50) CSFV "Shimen" strain. Observation of clinical signs was made and the existence of CSFV RNA was detected. Animals in the hAd-CMV and DMEM groups showed severe clinical CSF symptoms and were euthanized from 7 to 10 days after the challenge. However, no adverse clinical CSF signs were observed in vaccinated pigs after the administration of rAd-Erns-E2 and even after CSFV challenge. Neither CSFV RNA nor pathological changes were detected in the tissues of interest of the above vaccinated pigs. These results implied that the recombination adenovirus carrying the Erns-E2 genes could be used to prevent swine from classical swine fever.

  18. Birth defects in pregestational diabetes: Defect range,glycemic threshold and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Rinat Gabbay-Benziv; E Albert Reece; Fang Wang, Peixin Yang

    2015-01-01

    Currently, 60 million women of reproductive age(18-44 years old) worldwide, and approximately 3million American women have diabetes mellitus, andit has been estimated that this number will doubleby 2030. Pregestational diabetes mellitus (PGD) is asignificant public health problem that increases therisk for structural birth defects affecting both maternaland neonatal pregnancy outcome. The most commontypes of human structural birth defects associated withPGD are congenital heart defects and central nervoussystem defects. However, diabetes can induce birthdefects in any other fetal organ. In general, the rateof birth defects increases linearly with the degree ofmaternal hyperglycemia, which is the major factor thatmediates teratogenicity of PGD. Stringent prenatal careand glycemic control are effective means to reducebirth defects in PGD pregnancies, but cannot reducethe incidence of birth defects to the rate of that is seenin the nondiabetic population. Studies in animal modelshave revealed that PGD induces oxidative stress,which activates cellular stress signalling leading todysregulation of gene expression and excess apoptosisin the target organs, including the neural tube andembryonic heart. Activation of the apoptosis signalregulatingkinase 1 (ASK1)-forkhead transcription factor3a (FoxO3a)-caspase 8 pathway causes apoptosis in thedeveloping neural tube leading to neural tube defects(NTDs). ASK1 activates the c-Jun-N-Terminal kinase1/2 (JNK1/2), which leads to activation of the unfoldedprotein response and endoplasmic reticulum (ER) stress.Deletion of the ASK1 gene, the JNK1 gene, or the JNK2gene, or inhibition of ER stress by 4-Phenylbutyric acidabrogates diabetes-induced apoptosis and reduces theformation of NTDs. Antioxidants, such as thioredoxin,which inhibits the ASK1-FoxO3a-caspase 8 pathway orER stress inhibitors, may prevent PGD-induced birthdefects. Gabbay-Benziv R et al . Birth defects in pregestational diabetes

  19. Defects in Human Nature

    Institute of Scientific and Technical Information of China (English)

    黄靓

    2008-01-01

    By tracing the defects of society back to the defects of human nature, humanity's essence is proved to be inherent evil. Man's natural tendency to do evil remain harnessed through the controls and conventions imposed by civilization, however, when rules or civilization are weakened, man' s dark side is unleashed.

  20. School Building Defect Pattern

    Directory of Open Access Journals (Sweden)

    Mahli M.

    2014-01-01

    Full Text Available In providing a conducive learning environment for the student, the school building must be in good condition. This paper is evaluating the existing condition of primary school building in Sarawak, Malaysia. It focuses on building defects pattern for school building. The primary data collection is from the school building condition survey with involvement of 24 primary schools. The schools have been selected using simple random sampling and stratified sampling (of school age as the variable of selection. The reporting method is based on Condition Survey Protocol (CSP 1 Matrix. Data analysis covers descriptive and inferential statistics. The analysis carried out found that the overall 4,725 defects have been identified. The building defect pattern is mainly on Ground Level of 3,176 defects, the highest number of defects components found on walls (798. 16.2% defects are cracks from 11 common defects and most of all the highest score of defects based on age of the building were the building in the range of 11 to 20 years.

  1. Defects at oxide surfaces

    CERN Document Server

    Thornton, Geoff

    2015-01-01

    This book presents the basics and characterization of defects at oxide surfaces. It provides a state-of-the-art review of the field, containing information to the various types of surface defects, describes analytical methods to study defects, their chemical activity and the catalytic reactivity of oxides. Numerical simulations of defective structures complete the picture developed. Defects on planar surfaces form the focus of much of the book, although the investigation of powder samples also form an important part. The experimental study of planar surfaces opens the possibility of applying the large armoury of techniques that have been developed over the last half-century to study surfaces in ultra-high vacuum. This enables the acquisition of atomic level data under well-controlled conditions, providing a stringent test of theoretical methods. The latter can then be more reliably applied to systems such as nanoparticles for which accurate methods of characterization of structure and electronic properties ha...

  2. Cosmic defects and cosmology

    CERN Document Server

    Magueijo, J; Magueijo, Joao; Brandenberger, Robert

    2000-01-01

    We provide a pedagogical overview of defect models of structure formation. We first introduce the concept of topological defect, and describe how to classify them. We then show how defects might be produced in phase transitions in the Early Universe and approach non-pathological scaling solutions. A very heuristic account of structure formation with defects is then provided, following which we introduce the tool box required for high precision calculations of CMB and LSS power spectra in these theories. The decomposition into scalar vector and tensor modes is reviewed, and then we introduce the concept of unequal-time correlator. We use isotropy and causality to constrain the form of these correlators. We finally show how these correlators may be decomposed into eigenmodes, thereby reducing a defect problem to a series of ``inflation'' problems. We conclude with a short description of results in these theories and how they fare against observations. We finally describe yet another application of topological d...

  3. Familial Atrial Septal Defect and Sudden Cardiac Death

    DEFF Research Database (Denmark)

    Ellesøe, Sabrina Gade; Johansen, Morten Munk; Bjerre, Jesper Vandborg;

    2016-01-01

    OBJECTIVE: Atrial septal defect (ASD) is the second most common congenital heart defect (CHD) and is observed in families as an autosomal dominant trait as well as in nonfamilial CHD. Mutations in the NKX2-5 gene, located on chromosome 5, are associated with ASD, often combined with conduction...

  4. Genetics Home Reference: congenital bile acid synthesis defect type 2

    Science.gov (United States)

    ... DEFECT, CONGENITAL, 2 Sources for This Page Clayton PT. Disorders of bile acid synthesis. J Inherit Metab ... J, Duran M, Overmars H, Scambler PJ, Clayton PT. Mutations in SRD5B1 (AKR1D1), the gene encoding delta( ...

  5. Surface defects and symmetries

    Science.gov (United States)

    Fuchs, Jürgen; Schweigert, Christoph

    2015-04-01

    In quantum field theory, defects of various codimensions are natural ingredients and carry a lot of interesting information. In this contribution we concentrate on topological quantum field theories in three dimensions, with a particular focus on Dijkgraaf-Witten theories with abelian gauge group. Surface defects in Dijkgraaf-Witten theories have applications in solid state physics, topological quantum computing and conformal field theory. We explain that symmetries in these topological field theories are naturally defined in terms of invertible topological surface defects and are thus Brauer-Picard groups.

  6. Defect solitons in photonic lattices.

    Science.gov (United States)

    Yang, Jianke; Chen, Zhigang

    2006-02-01

    Nonlinear defect modes (defect solitons) and their stability in one-dimensional photonic lattices with focusing saturable nonlinearity are investigated. It is shown that defect solitons bifurcate out from every infinitesimal linear defect mode. Low-power defect solitons are linearly stable in lower bandgaps but unstable in higher bandgaps. At higher powers, defect solitons become unstable in attractive defects, but can remain stable in repulsive defects. Furthermore, for high-power solitons in attractive defects, we found a type of Vakhitov-Kolokolov (VK) instability which is different from the usual VK instability based on the sign of the slope in the power curve. Lastly, we demonstrate that in each bandgap, in addition to defect solitons which bifurcate from linear defect modes, there is also an infinite family of other defect solitons which can be stable in certain parameter regimes. PMID:16605473

  7. Screening Tests for Birth Defects

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Screening Tests for Birth Defects Home For Patients Search ... for Birth Defects FAQ165, April 2014 PDF Format Screening Tests for Birth Defects Pregnancy What is a ...

  8. Defect Prevention Based on 5 Dimensions of Defect Origin

    Directory of Open Access Journals (Sweden)

    Sakthi Kumaresh

    2012-08-01

    Full Text Available “Discovering the unexpected is more important than confirming the known [7]. In software development,the “unexpected” one relates to defects. These defects when unattended would cause failure to the productand risk to the users. The increasing dependency of society on software and the crucial consequences that afailure can cause requires the need to find out the defects at the origin itself. Based on the lessons learntfrom the earlier set of projects, a defect framework highlighting the 5 Dimensions (Ds of defect origin isproposed in this work. The defect framework is based on analyzing the defects that had emerged fromvarious stages of software development like Requirements, Design, Coding, Testing and Timeline (defectsdue to lack of time during development. This study is not limited to just identifying the origin of defects atvarious phases of software development but also finds out the reasons for such defects, and defectpreventive (DP measures are proposed for each type of defect. This work can help practitioners chooseeffective defect avoidance measures.In addition to arriving at defect framework, this work also proposes a defect injection metric based onseverity of the defect rather than just defect count, which gives the number of adjusted defects produced bya project at various phases. The defect injection metric value, once calculated, serves as a yardstick tomake a comparison in the improvements made in the software process development between similar set ofprojects

  9. Birth Defects (For Parents)

    Science.gov (United States)

    ... KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say Vaccines: Which ... there is a problem with a baby's body chemistry, it is called a metabolic birth defect. Metabolic ...

  10. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  11. Quantum computing with defects

    OpenAIRE

    Weber, J R; Koehl, W. F.; Varley, J. B.; Janotti, A.; Buckley, B. B.; Van de Walle, C. G.; Awschalom, D. D.

    2010-01-01

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV-1) center stands out for its robustness - its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar qua...

  12. Neural tube defects between folate metabolism and genetics

    Directory of Open Access Journals (Sweden)

    Helmi Y Alfarra

    2011-01-01

    Full Text Available Neural tube defects (NTDs are the second most common severely disabling human congenital defects. Worldwide, NTDs incidence is approximately one per 1000 live births and varies between 0.78 and 12 per 1000 births in general populations. NTDs causation involves multiple genes, nutritional and environmental factors. Research in the next stage should include bigger populations and bigger studies that would be suitable to detect significant links and conclusions with relatively minor risk factors; analysis of multiple candidate genes to detect potential gene-gene interactions; detailed analysis of patient samples stratified by phenotype.

  13. Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV

    Directory of Open Access Journals (Sweden)

    Ashfaq Usman Alli A

    2011-06-01

    Full Text Available Abstract Background/Aim Hepatitis C virus (HCV is a major threat as almost 3% of the world's population (350 million individual and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi, a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR, scavenger receptor class B type 1 (SR-B1, and Claudin1 (CLDN1. Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection. Results In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR, which resulted in a significant decrease in HCV viral copy number. Conclusion From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.

  14. Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE

    NARCIS (Netherlands)

    Dijkstra, S.; Kooij, G.; Verbeek, R.; Pol, S.M.A. van der; Amor, S.; Geisert Jr., E.E.; Dijkstra, C.D.; Noort, J.M. van; Vries, H.E.d.

    2008-01-01

    Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-assoc

  15. DEFECTS SIMULATION OF ROLLING STRIP

    OpenAIRE

    Rudolf Mišičko; Tibor Kvačkaj; Martin Vlado; Lucia Gulová; Miloslav Lupták; Jana Bidulská

    2009-01-01

    The defects in the continuous casting slabs can be developed or kept down in principle by rolling technology, especially depend to sort, size and distribution of primary defects, as well as used of rolling parameters. Scope of the article is on observation behavior artificial surface and undersurface defects (scores) without filler (surface defects) and filling by oxides and casting powder (subsurface defects). First phase of hot rolling process have been done by software simulation DEFORM 3D...

  16. Efficient Co-Replication of Defective Novirhabdovirus.

    Science.gov (United States)

    Rouxel, Ronan N; Mérour, Emilie; Biacchesi, Stéphane; Brémont, Michel

    2016-03-01

    We have generated defective Viral Hemorrhagic Septicemia Viruses (VHSV) which express either the green fluorescent protein (GFP) or a far-red fluorescent protein (mKate) by replacing the genes encoding the nucleoprotein N or the polymerase-associated P protein. To recover viable defective viruses, rVHSV-ΔN-Red and rVHSV-ΔP-Green, fish cells were co-transfected with both deleted cDNA VHSV genomes, together with plasmids expressing N, P and L of the RNA-dependent RNA polymerase. After one passage of the transfected cell supernatant, red and green cell foci were observed. Viral titer reached 10⁷ PFU/mL after three passages. Infected cells were always red and green with the very rare event of single red or green cell foci appearing. To clarify our understanding of how such defective viruses could be so efficiently propagated, we investigated whether (i) a recombination event between both defective genomes had occurred, (ii) whether both genomes were co-encapsidated in a single viral particle, and (iii) whether both defective viruses were always replicated together through a complementation phenomenon or even as conglomerate. To address these hypotheses, genome and viral particles have been fully characterized and, thus, allowing us to conclude that rVHSV-ΔN-Red and rVHSV-ΔP-Green are independent viral particles which could propagate only by simultaneously infecting the same cells. PMID:26959049

  17. Production of point defects

    International Nuclear Information System (INIS)

    Vacancies at thermodynamic equilibrium and the annealing of these defects are studied first, after which electron irradiations are dealt with. The displacement threshold energy concept is introduced. Part three concerns heavy ion and neutron irradiations. Displacement cascades and the thermal spike concept are discussed

  18. Quantum computing with defects.

    Science.gov (United States)

    Weber, J R; Koehl, W F; Varley, J B; Janotti, A; Buckley, B B; Van de Walle, C G; Awschalom, D D

    2010-05-11

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors. PMID:20404195

  19. Topological defects in CFT

    Energy Technology Data Exchange (ETDEWEB)

    Petkova, V. B., E-mail: petkova@inrne.bas.bg [Bulgarian Academy of Sciences, Institute of Nuclear Research and Nuclear Energy (Bulgaria)

    2013-10-15

    Areview of the notion, properties and the use of topological defects in 2d conformal field theories is presented. An emphasis is made on the recent interpretation of such operators in non-rational theories, as describing Wilson-'t Hooft loop operators of N = 2 supersymmetric 4d topological theories.

  20. Defects in flexoelectric solids

    Science.gov (United States)

    Mao, Sheng; Purohit, Prashant K.

    2015-11-01

    A solid is said to be flexoelectric when it polarizes in proportion to strain gradients. Since strain gradients are large near defects, we expect the flexoelectric effect to be prominent there and decay away at distances much larger than a flexoelectric length scale. Here, we quantify this expectation by computing displacement, stress and polarization fields near defects in flexoelectric solids. For point defects we recover some well known results from strain gradient elasticity and non-local piezoelectric theories, but with different length scales in the final expressions. For edge dislocations we show that the electric potential is a maximum in the vicinity of the dislocation core. We also estimate the polarized line charge density of an edge dislocation in an isotropic flexoelectric solid which is in agreement with some measurements in ice. We perform an asymptotic analysis of the crack tip fields in flexoelectric solids and show that our results share some features from solutions in strain gradient elasticity and piezoelectricity. We also compute the energy release rate for cracks using simple crack face boundary conditions and use them in classical criteria for crack growth to make predictions. Our analysis can serve as a starting point for more sophisticated analytic and computational treatments of defects in flexoelectric solids which are gaining increasing prominence in the field of nanoscience and nanotechnology.

  1. Quantum computing with defects.

    Science.gov (United States)

    Weber, J R; Koehl, W F; Varley, J B; Janotti, A; Buckley, B B; Van de Walle, C G; Awschalom, D D

    2010-05-11

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors.

  2. Phenotype of adult Refsum disease due to a defect in peroxin 7.

    Science.gov (United States)

    Horn, M A; van den Brink, D M; Wanders, R J A; Duran, M; Poll-The, B T; Tallaksen, C M E; Stokke, O H; Moser, H; Skjeldal, O H

    2007-02-27

    The biochemical hallmark of adult Refsum disease (ARD) is an isolated deficiency in the breakdown of phytanic acid. This usually results from a PHYH gene defect, although some cases have been found to carry a PEX7 defect. We describe the phenotype of such a patient, indistinguishable from that of classic ARD. Hence, we propose the subdivision of ARD into type 1 and type 2, depending on which gene is defective.

  3. Syndromic ectrodactyly with severe limb, ectodermal, urogenital, and palatal defects maps to chromosome 19

    OpenAIRE

    O'Quinn, J.; Hennekam, R.C.M.; Jorde, L B; Bamshad, M

    1998-01-01

    Congenital limb malformations rank behind only congenital heart disease as the most common birth defects observed in infants. Finding genes that cause defects in human limb patterning should be straightforward but has been limited, in part, by the bewildering spectrum of phenotypes, which are difficult to separate into etiologically distinct disorders. One approach to the identification of relevant genes is to take advantage of unique extended kindreds in which a defect in limb patterning is ...

  4. Defect identification by compositional defect review using auger electron spectroscopy

    International Nuclear Information System (INIS)

    Defect identification plays an enabling role in determining the source of particles that occur during semiconductor processing and are subsequently detected by defect inspection tools. Auger electron spectroscopy provides a high spatial resolution, surface sensitive analytical probe that is well matched to examining small, thin or complex defects. A focused ion beam (FIB) can be used to cross-section buried defects and structures for subsequent Auger analysis. Such measurements have been made on defects from two wafers pulled at different process steps. One wafer was analyzed after poly-Si deposition, and the other wafer was analyzed after metal 2 etch. The defects on the poly-Si wafer are Si particles. Three types of particles were found on the metal 2 wafer: C-based, stainless steel, and Si-oxide. The majority of defects on this wafer are C-based. Auger, EDS and FIB results will be compared for representative defects on these two wafers

  5. UNBINDING OF SURFACE DEFECTS UNDER THE DEFECT-SELECTIVE ADSORPTION

    Directory of Open Access Journals (Sweden)

    E.V.Vakarin

    2003-01-01

    Full Text Available Unbinding of surface topological defects in the presence of the defect-selective adsorption is investigated using a coupled Coulomb Gas - Lattice Gas model. The unbinding temperature increases with the increasing selectivity (and coverage for both, sign-dependent and sign-independent adsorption. In the latter case, the adsorbates tend to increase the number density of defects. The stability requirement implies that the adsorbate cluster size must be coherent with the screening length of free defects.

  6. Immune deficiencies due to defects in cytokine signaling.

    Science.gov (United States)

    Kelly, John; Leonard, Warren J

    2003-09-01

    Severe combined immunodeficiency (SCID) represents a syndrome comprising the most severe forms of inherited immunodeficiencies. Defects in cytokine signaling pathways can result in impaired development of lymphoid cells and/or defective functioning of these cells, and most cases of SCID result from defective signaling through the common cytokine receptor g chain (g(c)) or associated molecules and signaling pathways. Studies of these patients and the analysis of gene-targeted mice provide insight into the underlying signaling defects in inherited immunodeficiencies. The identification of the genetic defects in humans with SCID provides the basis for future therapies for these patients. More subtle deficiencies in cytokine signaling have also been found as causes of other forms of immunodeficiency, and the knowledge learned could lead to novel approaches to antimicrobial therapy. PMID:12906775

  7. Point defects in silicates

    International Nuclear Information System (INIS)

    Topaz is a wide band gap insulating crystal with four Al2F2SiO4 formula units per orthorhombic unit cell and containing isolated SiO4 tetrahedron. Electron spin resonance (ESR), UV-VIS spectrophotometry, photoluminescence, and isochronal annealing were used to study the point defects introduced by fast-neutron bombardment or by alpha decay recoils. The superoxide radical is characterized by a single hole-like spin 1/2 signal with principle g-values gxx = 2.0055, gzz = 2.0407 and the major axis of the defect points along 0.356a + 0.152b + 0.922c. The superoxide anneals near 650C. Two polarization dependent absorptions occur in the UV due to the transitions 2IIg → 2IIu and 2IIg → 2Δu. The former has an oscillator strength of 0.06. The 2.5 eV polarization dependent luminescence is due to the transition 2IIg → 2IIu. The 2Δu → 2IIu is non-radiative. The doubly occupied dangling silicon bond, the blue center, is characterized by a 2 eV polarization dependent absorption and is non-paramagnetic. The transition dipole for this absorption points in the direction 0.93a + 0.210b + 0.305c and the oscillator strength is approximately 2.0 x 10-3. The blue center anneals at 500C. This dangling bond defect is one of two models proposed for a similar 2 eV absorption in silica glass. The defects in quartz (SiO2) were introduced by the recoil nuclei after alpha decays of uranium, thorium, and their daughters in natural abundances. The accumulating damage provides a geological clock by which the age of the quartz can be found. The sample came from Yucca Flats, Nevada, the proposed site of a nuclear waste dump

  8. Mask Blank Defect Detection

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, M A; Sommargren, G E

    2000-02-04

    Mask blanks are the substrates that hold the master patterns for integrated circuits. Integrated circuits are semiconductor devices, such as microprocessors (mPs), dynamic random access memory (DRAMs), and application specific integrated circuits (ASICs) that are central to the computer, communication, and electronics industries. These devices are fabricated using a set of master patterns that are sequentially imaged onto light-sensitive coated silicon wafers and processed to form thin layers of insulating and conductive materials on top of the wafer. These materials form electrical paths and transistors that control the flow of electricity through the device. For the past forty years the semiconductor industry has made phenomenal improvements in device functionality, compactness, speed, power, and cost. This progress is principally due to the exponential decrease in the minimum feature size of integrated circuits, which has been reduced by a factor of {radical}2 every three years. Since 1992 the Semiconductor Industry Association (SIA) has coordinated the efforts of producing a technology roadmap for semiconductors. In the latest document, ''The International Technology Roadmap for Semiconductors: 1999'', future technology nodes (minimum feature sizes) and targeted dates were specified and are summarized in Table 1. Lithography is the imaging technology for producing a de-magnified image of the mask on the wafer. A typical de-magnification factor is 4. Mask blank defects as small as one-eighth the equivalent minimum feature size are printable and may cause device failure. Defects might be the result of the surface preparation, such as polishing, or contamination due to handling or the environment. Table 2 shows the maximum tolerable defect sizes on the mask blank for each technology node. This downward trend puts a tremendous burden on mask fabrication, particularly in the area of defect detection and reduction. A new infrastructure for mask

  9. High throughput functional genomics: identification of novel genes with tumor suppressor phenotypes.

    Science.gov (United States)

    Koenig-Hoffmann, Kerstin; Bonin-Debs, Angelika L; Boche, Irene; Gawin, Beate; Gnirke, Andrea; Hergersberg, Christoph; Madeo, Frank; Kazinski, Michael; Klein, Matthias; Korherr, Christian; Link, Dieter; Röhrig, Sascha; Schäfer, Rolf; Brinkmann, Ulrich

    2005-01-20

    We have used a combination of high throughput functional genomics, computerized database mining and expression analyses to discover novel human tumor suppressor genes (TSGs). A genome-wide high throughput cDNA phenotype screen was established to identify genes that induce apoptosis or reduce cell viability. TSGs are expressed in normal tissue and frequently act by reduction of growth of transformed cells or induce apoptosis. In agreement with that and thus serving as platform validation, our pro-apoptotic hits included genes for which tumor suppressing activities were known, such as kangai1 and CD81 antigen. Additional genes that so far have been claimed as putative TSGs or associated with tumor inhibitory activities (prostate differentiation factor, hRAS-like suppressor 3, DPH2L1-like and the metastasis inhibitor Kiss1) were confirmed in their proposed TSG-like phenotype by functionally defining their growth inhibitory or pro-apoptotic function towards cancer cells. Finally, novel genes were identified for which neither association with cell growth nor with apoptosis were previously described. A subset of these genes show characteristics of TSGs because they (i) reduce the growth or induce apoptosis in tumor cells; (ii) show reduced expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH-) loci for which cancer-associated deletions are described. The pro-apoptotic phenotype and differential expression of these genes in normal and malignant tissue make them promising target candidates for the diagnosis and therapy of various tumors.

  10. Defect disorder in UO2

    International Nuclear Information System (INIS)

    A defect disorder model has been developed to determine equilibrium off-stoichiometry and its spatial variations in UO2 crystals. The model gives the concentrations of atomic defects and electronic carriers as functions of oxygen partial pressure and temperature in the bulk and near crystal surfaces subject to an oxygen environment. Energetic parameters from published density functional theory calculations have been integrated into the defect disorder model for an accurate determination of the defect density and off-stoichiometry. The ionosorption theory has been used to couple the oxygen environment with the defect state in the crystal as we solved for the defect disorder near crystal surfaces. Contrary to the common belief that hyper-stoichiometry of UO2 is dominated by oxygen interstitials, the current model predicts that this regime is rather dominated by uranium vacancies. The model predictions also show that, in the presence of surfaces, the point defect concentrations vary by orders of magnitude in the subsurface region relative to the bulk region. Highlights: • Defect disorder in bulk UO2+x is modeled in terms of temperature and oxygen pressure. • The densities of atomic defects and electronic charge carriers are determined. • The model is extended to study the heterogeneity of defect density near crystal surfaces. • The surface effect is modeled using ionosorption theory. • The dominant defect type and off-stoichiometry profile near surface are found

  11. Defect Recognition in Thermosonic Imaging

    Institute of Scientific and Technical Information of China (English)

    CHEN Dapeng; WU Naiming; ZHANG Zheng

    2012-01-01

    This work is aimed at developing an effective method for defect recognition in thermosonic imaging.The heat mechanism of thermosonic imaging is introduced,and the problem for defect recognition is discussed.For this purpose,defect existing in the inner wall of a metal pipeline specimen and defects embedded in a carbon fiber reinforced plastic (CFRP) laminate are tested.The experimental data are processed by pulse phase thermography (PPT) method to show the phase images at different frequencies,and the characteristic of phase angle vs frequency curve of thermal anomalies and sound area is analyzed.A binary image,which is based on the characteristic value of defects,is obtained by a new recognition algorithm to show the defects.Results demonstrate good defect recognition performance for thermosonic imaging,and the reliability of this technique can be improved by the method.

  12. Observación y cuantificación de defectos en soldaduras a través del procesamiento digital de imágenes termográficas//Defects in weld observation and quantification through digital thermographic images processing

    Directory of Open Access Journals (Sweden)

    Eriel Pérez-Zapico

    2013-09-01

    Full Text Available El objetivo del trabajo fue la observación y cuantificación de defectos en soldaduras a través del procesamiento digital de imágenes termográficas, mediante la termografía activa con sistema de calentamiento por conducción y enfriamiento natural en aire. Se ensayaron dos probetas soldadas de acero estructural con discontinuidades subsuperficiales, se dispuso la cámara infrarroja perpendicular alas probetas y se obtuvieron las imágenes durante el enfriamiento. El algoritmo para el procesamiento digital de las imágenes infrarrojas se basó en la conversión a escala de grises de las imágenes, la aplicación de filtros y operaciones morfológicas para la cuantificación de los defectos. Se observaron poros, inclusiones de escoria y falta de fusión y se cuantificó geométricamente su longitud y perímetro. El método se confrontó mediante la técnica de inspección por radiografía, apreciándose un error inferior al 3,4 %. Esta técnica pudiera emplearse como preevaluación para calificar procedimientos de soldadura y soldadores.Palabras claves: imágenes termográficas, defectos en soldadura, procesamientos digitales.______________________________________________________________________________AbstractThe objective of this paper was the observation and quantification through the digital thermographic images processing of defect in welds, the active thermography method with a conduction heat and cooling in natural air system means. Two structural steel welded specimens with internal discontinuities weretested; the infrarred camera was placed perpendicular to the specimens and was obtained the images during the cooling. The infrared images digital processing algorithm was based on the conversion of the images to scale of gray, filters and morphological operations application for quantification the defects.Pores, slag inclusions and lack of fusion were observed and geometric longitude and perimeter were too. The method was confronted by

  13. Amphid defective mutant of Caenorhabditis elegans.

    Science.gov (United States)

    De Riso, L; Ristoratore, F; Sebastiano, M; Bazzicalupo, P

    1994-01-01

    Studies are reported on a chemoreception mutant which arose in a mutator strain. The mutant sensory neurons do not stain with fluoresceine isothiocyanate (Dyf phenotype), hence the name, dyf-1, given to the gene it identifies. The gene maps on LGI, 0.4 map units from dpy-5 on the unc-11 side. The response of mutant worms to various repellents has been studied and shown to be partially altered. Other chemoreception based behaviors are less affected. The cilia of the sensory neurons of the amphid are shorter than normal and the primary defect may be in the capacity of the sheath cells to secrete the matrix material that fills the space between cilia in the amphid channel. Progress toward the molecular cloning of the gene is also reported. Relevant results from other laboratories are briefly reviewed. PMID:7896139

  14. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  15. The effects of BMP-2 gene medication on the reconstruction of osteolytic bone defect around implant%假体周围骨溶解性骨缺损的转骨形态发生蛋白-2基因治疗

    Institute of Scientific and Technical Information of China (English)

    严孟宁; 戴尅戎; 汤亭亭

    2008-01-01

    目的 模拟假体周围骨溶解环境,观察骨形态发生蛋白-2(BMP-2)基因治疗假体周围骨溶解性骨缺损的效果.方法 成年雄性Beagle犬6条,于股骨外髁造成假体周围3mm骨缺损区.1条动物的左侧缺损区植入1ml平均直径1μm的钛合金颗粒混悬液,右侧植入1ml磷酸盐缓冲液(PBS),观察造模结果;其他5条动物双侧植入1ml钛合金颗粒混悬液,于术后2个月取出假体,植入转BMP-2基因冻干骨或单纯冻干骨,二次术后3个月取材,行组织学、组织形态计量学观察植骨愈合替代及界面骨整合情况.结果 颗粒造模术后2个月可见典型的骨溶解界膜组织形成.翻修术后3个月,冻干骨组见较多植骨残余,假体-骨界面基本为软组织界膜,假体骨接触率(BIC)为(1.38±1.22)%;基因治疗组见少量植骨残余,假体-骨界面有点状骨接触,BIC为(12.96±1.61)%,两组差异有统计学意义(P<0.01).结论 采用BMP-2基因治疗可提高假体周围骨溶解性骨缺损的界面骨整合.%Objective With the osteolystic model,the simulating revision was done to investigate the effects of BMP-2 gene therapy on the reconstruction of periprosthetic bone defect.Methods A 3 mm bone defect around Ti alloy implant was created in both femoral lateral condyla of 6 adult Beagle dogs.One animal was left as a model to evaluate the effects of particles on the defect,with 1 ml Ti alloy particles averaged diameter of 1μm implanted on the left bone defect and 1 ml PBS on the right.Ten defects of the other 5 animals were implanted 1 ml Ti alloy particle and the revisions were done 2 months postoperatively.With the impaction grafting technique,two defects of each animal were reconstructed with freeze-dried allograft (FDB group),freeze-dried allograft loading autogenous bone marrow stromal cells transfected by Adv-BMP2 gene (gene group) respectively.The allograft healing and osseointegration of bone-implant interface were evaluated by histological

  16. Investigation of plasmid-induced growth defect in Pseudomonas putida.

    Science.gov (United States)

    Mi, Jia; Sydow, Anne; Schempp, Florence; Becher, Daniela; Schewe, Hendrik; Schrader, Jens; Buchhaupt, Markus

    2016-08-10

    Genetic engineering in bacteria mainly relies on the use of plasmids. But despite their pervasive use for physiological studies as well as for the design and optimization of industrially used production strains, only limited information about plasmid induced growth defects is available for different replicons and organisms. Here, we present the identification and characterization of such a phenomenon for Pseudomonas putida transformants carrying the pBBR1-derived plasmid pMiS1. We identified the kanamycin resistance gene and the transcription factor encoding rhaR gene to be causal for the growth defect in P. putida. In contrast, this effect was not observed in Escherichia coli. The plasmid-induced growth defect was eliminated after introduction of a mutation in the plasmid-encoded rep gene, thus enabling construction of the non-toxic variant pMiS4. GFP reporters construct analyses and qPCR experiments revealed a distinctly lowered plasmid copy number for pMiS4, which is probably the reason for alleviation of the growth defect by this mutation. Our work expands the knowledge about plasmid-induced growth defects and provides a useful low-copy pBBR1 replicon variant. PMID:27287537

  17. Studies of defects and defect agglomerates by positron annihilation spectroscopy

    DEFF Research Database (Denmark)

    Eldrup, Morten Mostgaard; Singh, B.N.

    1997-01-01

    A brief introduction to positron annihilation spectroscopy (PAS), and in particular lo its use for defect studies in metals is given. Positrons injected into a metal may become trapped in defects such as vacancies, vacancy clusters, voids, bubbles and dislocations and subsequently annihilate from...... advantages of the use of PAS are pointed out. (C) 1997 Elsevier Science B.V....

  18. Site-directed mutagenesis of HIV-1 vpu gene demonstrates two clusters of replication-defective mutants with distinct ability to down-modulate cell surface CD4 and tetherin

    Directory of Open Access Journals (Sweden)

    Masako Nomaguchi

    2010-11-01

    Full Text Available HIV-1 Vpu acts positively on viral infectivity by mediating CD4 degradation in endoplasmic reticulum and enhances virion release by counteracting a virion release restriction factor, tetherin. In order to define the impact of Vpu activity on HIV-1 replication, we have generated a series of site-specific proviral vpu mutants. Of fifteen mutants examined, seven exhibited a replication-defect similar to that of a vpu-deletion mutant in a lymphocyte cell line H9. These mutations clustered in narrow regions within transmembrane domain (TMD and cytoplasmic domain (CTD. Replication-defective mutants displayed the reduced ability to enhance virion release from a monolayer cell line HEp2 without exception. Upon transfection with Vpu expression vectors, neither TMD mutants nor CTD mutants blocked CD4 expression at the cell surface in another monolayer cell line MAGI. While TMD mutants were unable to down-modulate cell surface tetherin in HEp2 cells, CTD mutants did quite efficiently. Confocal microscopy analysis revealed the difference of intracellular localization between TMD and CTD mutants. In total, replication capability of HIV-1 carrying vpu mutations correlates well with the ability of Vpu to enhance virion release and to impede the cell surface expression of CD4 but not with the ability to down-modulate cell surface tetherin. Our results here suggest that efficient viral replication requires not only down-regulation of cell surface tetherin but also its degradation.

  19. Methionine synthase reductase deficiency results in adverse reproductive outcomes and congenital heart defects in mice

    OpenAIRE

    Deng, Liyuan; Elmore, C. Lee; Lawrance, Andrea K.; Matthews, Rowena G.; Rozen, Rima

    2008-01-01

    Low dietary folate and polymorphisms in genes of folate metabolism can influence risk for pregnancy complications and birth defects. Methionine synthase reductase (MTRR) is required for activation of methionine synthase, a folate- and vitamin B12-dependent enzyme. A polymorphism in MTRR (p.I22M), present in the homozygous state in 25% of many populations, may increase risk for neural tube defects. To examine the impact of MTRR deficiency on early development and congenital heart defects, we u...

  20. Irradiation Defects in Silicon Crystal

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The application of irradiation in silicon crystal is introduced.The defects caused by irradiation are reviewed and some major ways of studying defects in irradiated silicon are summarized.Furthermore the problems in the investigation of irradiated silicon are discussed as well as its properties.

  1. Holographic Chern-Simons Defects

    CERN Document Server

    Fujita, Mitsutoshi; Meyer, Rene; Sugimoto, Shigeki

    2016-01-01

    We study SU(N) Yang-Mills-Chern-Simons theory in the presence of defects that shift the Chern-Simons level from a holographic point of view by embedding the system in string theory. The model is a D3-D7 system in Type IIB string theory, whose gravity dual is given by the AdS soliton background with probe D7-branes attaching to the AdS boundary along the defects. We holographically renormalize the free energy of the defect system with sources, from which we obtain the correlation functions for certain operators naturally associated to these defects. We find interesting phase transitions when the separation of the defects as well as the temperature are varied. We also discuss some implications for the Fractional Quantum Hall Effect and for two-dimensional QCD.

  2. Holographic Chern-Simons defects

    Science.gov (United States)

    Fujita, Mitsutoshi; Melby-Thompson, Charles M.; Meyer, René; Sugimoto, Shigeki

    2016-06-01

    We study SU( N ) Yang-Mills-Chern-Simons theory in the presence of defects that shift the Chern-Simons level from a holographic point of view by embedding the system in string theory. The model is a D3-D7 system in Type IIB string theory, whose gravity dual is given by the AdS soliton background with probe D7 branes attaching to the AdS boundary along the defects. We holographically renormalize the free energy of the defect system with sources, from which we obtain the correlation functions for certain operators naturally associated to these defects. We find interesting phase transitions when the separation of the defects as well as the temperature are varied. We also discuss some implications for the Fractional Quantum Hall Effect and for 2-dimensional QCD.

  3. Particle gun-mediated bone morphogenetic protein-2 gene transfection for treatment of chronic bone defects%基因枪介导的骨形态发生蛋白2基因转染治疗陈旧性骨缺损

    Institute of Scientific and Technical Information of China (English)

    朱小萌; 王翀; 宋兴华; 詹玉林; 李文举

    2014-01-01

    背景:体内外研究都已证实骨形态发生蛋白具有调节成骨细胞和成软骨细胞的分化、诱导异位骨形成、促进骨折愈合、控制哺乳动物骨骼不同形态特征形成的功能。  目的:使用含有骨形态发生蛋白2基因真核表达质粒的基因枪进行局部基因注射以治疗陈旧骨缺损。  方法:72只新西兰大白兔建立陈旧兔桡骨中段骨缺损模型,按所截骨长度均分1.5 cm组、2.0 cm和2.5 cm组。各组又随机分为治疗组(骨形态发生蛋白2基因转染组)和对照组(自然愈合组)。于转染后1,3,8,9周拍摄X射线平片,1,3,8和9周取骨折间软组织行骨形态发生蛋白2的Western blot检测,于1,3,8和9周时取标本大体观察,评价愈合情况。  结果与结论:①大体标本观察发现治疗组骨痂生成量多于对照组。②治疗组转染后1,3,8,9周的Lane-Sandhu X射线评分优于对照组,差异均有显著性意义(P OBJECTIVE:To treat chronic bone defects using particle gun containing BMP2 gene eukaryotic expression plasmid via local injection. METHODS:A total of 72 healthy New Zealand white rabbits were applied to establish chronic bone defect model in the rabbit radius. According to the length of bone defect, the rabbits were divided into three groups:1.5 cm group, 2.0 cm group, 2.5 cm group. Each group was further randomly assigned into two subgroups:treatment group (BMP-2 gene transfection) and control group (natural y healing). X-ray examinations were performed at 1, 3, 8 and 9 weeks after transfection, and soft tissue between the bone defects was harvested to detect BMP-2 using western blot analysis;and radius specimens were taken for gross observation at the same time points, to evaluate the healing. RESULTS AND CONCLUSION:(1) Gross specimen observation:bone cal us formation in treatment group was general y more than that in control group. (2) Lane-Sandhu X-ray score in treatment group

  4. Holographic Experiments on Defects

    CERN Document Server

    Wapler, Matthias C

    2009-01-01

    Using the AdS/CFT correspondence, we study the anisotropic charge transport properties of both supersymmetric and non-supersymmetric matter fields on (2+1)-dimensional defects coupled to a (3+1)-dimensional ${\\cal N}=4$ SYM "heat bath". We focus on the case of a finite external background magnetic field, finite net charge density and finite mass. At high frequencies, we discover a spectrum of quasiparticle resonances due to the magnetic field and finite density and at small frequencies, we perform a Drude-like expansion around the DC limit. Both of these regimes display many generic features and some features that we attribute to strong coupling, such as a minimum DC conductivity and an unusual behavior of the "cyclotron" and plasmon frequencies, which become related to the resonances found in the conformal case in an earlier paper. We further study the hydrodynamic regime and the relaxation properties, from which the system displays a set of different possible transitions to the collisionless regime. The mas...

  5. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease.

    NARCIS (Netherlands)

    A.M. Sijbers (Anneke); W.L. de Laat (Wouter); R.A. Ariza (Rafael); M. Biggerstaff (Maureen); Y-F. Wei; J.G. Moggs (Jonathan); K.C. Carter (Kenneth); B.K. Shell (Brenda); E. Evans (Elizabeth); M.C. de Jong (Mariska); S. Rademakers (Suzanne); J.D. de Rooij (Johan); N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan); R.D. Wood (Richard)

    1996-01-01

    textabstractNucleotide excision repair, which is defective in xeroderma pigmentosum (XP), involves incision of a DNA strand on each side of a lesion. We isolated a human gene homologous to yeast Rad1 and found that it corrects the repair defects of XP group F as well as rodent groups 4 and 11. Causa

  6. Crohn's disease-Defect in innate defence

    Institute of Scientific and Technical Information of China (English)

    Michael Gersemann; Jan Wehkamp; Klaus Fellermann; Eduard Friedrich Stange

    2008-01-01

    Crohn's disease may prinicipally involve the whole gastrointestinal tract. Most commonly, the inflammation occurs in the small intestine and/or in the colon with stable disease location over the years. The pathogenesis of both disease phenotypes is complex, the likely primary defect lies in the innate rather than adaptive immunity, particularly in the chemical antimicrobial barrier of the mucosa Crohn's ileitis is associated with a reduced expression of the Wnt signalling pathway transcription factor T-cell factor 4 (TCF4) ,which is regulating Paneth cell differentiation. As a result, the alpha-defensins and principal Paneth cell products HD5 and HD6 are deficiently expressed in ileal disease, independent of current inflammation. In contrast, Crohn's colitis is typically associated with an impaired induction of the beta-defensins HBD2 and HBD3 caused by fewer gene copy numbers in the gene locus of the beta-defensins on chromosome 8. This ileal and colonic defect in innate defence mediated by a deficiency of the protective alpha- and betadefensins may enable the luminal microbes to invade the mucosa and trigger the inflammation. A better understanding of the exact molecular mechanisms behind ileal and colonic Crohn's disease may give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.(C)2008 The WJG Press. All fights reserved.

  7. Neural Tube Defects: From a Proteomic Standpoint

    Directory of Open Access Journals (Sweden)

    Tania M. Puvirajesinghe

    2015-03-01

    Full Text Available Neural tube defects (NTDs are congenital birth defects classified according to their resulting morphological characteristics in newborn patients. Current diagnosis of NTDs relies largely on the structural evaluation of fetuses using ultrasound imaging, with biochemical characterization used as secondary screening tools. The multigene etiology of NTDs has been aided by genetic studies, which have discovered panels of genes mutated in these diseases that encode receptors and cytoplasmic signaling molecules with poorly defined functions. Animal models ranging from flies to mice have been used to determine the function of these genes and identify their associated molecular cascades. More emphasis is now being placed on the identification of biochemical markers from clinical samples and model systems based on mass spectrometry, which open novel avenues in the understanding of NTDs at protein, metabolic and molecular levels. This article reviews how the use of proteomics can push forward the identification of novel biomarkers and molecular networks implicated in NTDs, an indispensable step in the improvement of patient management.

  8. Gene therapy: progress and predictions

    OpenAIRE

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of ...

  9. 2010 Defects in Semiconductors GRC

    Energy Technology Data Exchange (ETDEWEB)

    Shengbai Zhang

    2011-01-06

    Continuing its tradition of excellence, this Gordon Conference will focus on research at the forefront of the field of defects in semiconductors. The conference will have a strong emphasis on the control of defects during growth and processing, as well as an emphasis on the development of novel defect detection methods and first-principles defect theories. Electronic, magnetic, and optical properties of bulk, thin film, and nanoscale semiconductors will be discussed in detail. In contrast to many conferences, which tend to focus on specific semiconductors, this conference will deal with point and extended defects in a broad range of electronic materials. This approach has proved to be extremely fruitful for advancing fundamental understanding in emerging materials such as wide-band-gap semiconductors, oxides, sp{sup 2} carbon based-materials, and photovoltaic/solar cell materials, and in understanding important defect phenomena such as doping bottleneck in nanostructures and the diffusion of defects and impurities. The program consists of about twenty invited talks and a number of contributed poster sessions. The emphasis should be on work which has yet to be published. The large amount of discussion time provides an ideal forum for dealing with topics that are new and/or controversial.

  10. Serine biosynthesis and transport defects.

    Science.gov (United States)

    El-Hattab, Ayman W

    2016-07-01

    l-serine is a non-essential amino acid that is biosynthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, l-serine is a potent neurotrophic factor and a precursor of a number of essential compounds including phosphatidylserine, sphingomyelin, glycine, and d-serine. Serine biosynthesis defects result from impairments of PGDH, PSAT, or PSP leading to systemic serine deficiency. Serine biosynthesis defects present in a broad phenotypic spectrum that includes, at the severe end, Neu-Laxova syndrome, a lethal multiple congenital anomaly disease, intermediately, infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end, the childhood disease with intellectual disability. A serine transport defect resulting from deficiency of the ASCT1, the main transporter for serine in the central nervous system, has been recently described in children with neurological manifestations that overlap with those observed in serine biosynthesis defects. l-serine therapy may be beneficial in preventing or ameliorating symptoms in serine biosynthesis and transport defects, if started before neurological damage occurs. Herein, we review serine metabolism and transport, the clinical, biochemical, and molecular aspects of serine biosynthesis and transport defects, the mechanisms of these diseases, and the potential role of serine therapy. PMID:27161889

  11. Software Defect Detection with Rocus

    Institute of Scientific and Technical Information of China (English)

    Yuan Jiang; Ming Li; Zhi-Hua Zhou

    2011-01-01

    Software defect detection aims to automatically identify defective software modules for efficient software test in order to improve the quality of a software system. Although many machine learning methods have been successfully applied to the task, most of them fail to consider two practical yet important issues in software defect detection. First, it is rather difficult to collect a large amount of labeled training data for learning a well-performing model; second, in a software system there are usually much fewer defective modules than defect-free modules, so learning would have to be conducted over an imbalanced data set. In this paper, we address these two practical issues simultaneously by proposing a novel semi-supervised learning approach named Rocus. This method exploits the abundant unlabeled examples to improve the detection accuracy, as well as employs under-sampling to tackle the class-imbalance problem in the learning process. Experimental results of real-world software defect detection tasks show that Rocgs is effective for software defect detection. Its performance is better than a semi-supervised learning method that ignores the class-imbalance nature of the task and a class-imbalance learning method that does not make effective use of unlabeled data.

  12. DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects

    NARCIS (Netherlands)

    Kessler, K.; Wunderlich, I.; Uebe, S.; Falk, N.S.; Giessl, A.; Brandstatter, J.H.; Popp, B.; Klinger, P.; Ekici, A.B.; Sticht, H.; Dorr, H.G.; Reis, A.; Roepman, R.; Seemanova, E.; Thiel, C.T.

    2015-01-01

    Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. Th

  13. DEFECTS SIMULATION OF ROLLING STRIP

    Directory of Open Access Journals (Sweden)

    Rudolf Mišičko

    2009-06-01

    Full Text Available The defects in the continuous casting slabs can be developed or kept down in principle by rolling technology, especially depend to sort, size and distribution of primary defects, as well as used of rolling parameters. Scope of the article is on observation behavior artificial surface and undersurface defects (scores without filler (surface defects and filling by oxides and casting powder (subsurface defects. First phase of hot rolling process have been done by software simulation DEFORM 3D setting to the limited condition for samples with surface defects. Samples of material with low-carbon steel of sizes h x b x l have been chosen and the surface defects shape „U” and „V” of scores have been injected artificially by software. The process of rolling have been simulated on the deformation temperatures 1200°C and 900°C, whereas on the both of this deformation temperatures have been applied amount of deformation 10 and 50 %. With respect to the process of computer simulation, it is not possible to truthful real oxidation condition (physical – chemical process during heat of metal, in the second phase of our investigation have been observed influence of oxides and casting powders inside the scores for a defect behavior in plastic deformation process (hot and cold rolling process in laboratory condition. The basic material was STN steel class 11 375, cladding material was steel on the bases C-Mn-Nb-V. Scores have been filled by scales to get from the heating temperatures (1100°C a 1250°C, varied types of casting powders, if you like mixture of scale and casting powders in the rate 1:4. The joint of the basic and cladding material have been done by peripheral welded joint. Experiment results from both phases are pointed on the evolution of original typology defects in rolling process.

  14. [Insertional mutation in the AZOBR_p60120 gene is accompanied by defects in the synthesis of lipopolysaccharide and calcofluor-binding polysaccharides in the bacterium Azospirillum brasilense Sp245].

    Science.gov (United States)

    Katsy, E I; Prilipov, A G

    2015-03-01

    In the bacterium Azospirillum brasilense Sp245, extracellular calcofluor-binding polysaccharides (Cal+ phenotype) and two types of lipopolysaccharides, LPSI and LPSII, were previously identified. These lipopolysaccharides share the same repeating O-polysaccharide unit but have different antigenic structures and different charges of their O-polysaccharides and/or core oligosaccharides. Several dozens of predicted genes involved in the biosynthesis of polysaccharides have been localized in the AZOBR_p6 plasmid of strain Sp245 (GenBank accession no. HE577333). In the present work, it was demonstrated that an artificial transposon Omegon-Km had inserted into the central region of the AZOBR_p60120 gene in the A. brasilense Sp245 LPSI- Cal- KM252 mutant. In A. brasilense strain Sp245, this plasmid gene encodes a putative glycosyltransferase containing conserved domains characteristic of the enzymes participating in the synthesis of O-polysaccharides and capsular polysaccharides (accession no. YP004987664). In mutant KM252, a respective predicted protein is expected to be completely inactivated. As a result of the analysis of the EcoRI fragment of the AZOBR_p6 plasmid, encompassing the AZOBR_p60120 gene and a number of other loci, novel data on the structure of AZOBR_p6 were obtained: an approximately 5-kb gap (GenBank accession no. KM189439) was closed in the nucleotide sequence of this plasmid.

  15. The Arabidopsis male-sterile mutant dde2-2 is defective in the ALLENE OXIDE SYNTHASE gene encoding one of the key enzymes of the jasmonic acid biosynthesis pathway

    DEFF Research Database (Denmark)

    von Malek, Bernadette; van der Graaff, Eric; Schneitz, Kay;

    2002-01-01

    exhibits a male-sterile phenotype. The dde2-2 phenotype can be rescued by application of methyl jasmonate, indicating that the mutant is affected in jasmonic acid biosynthesis. The combination of genetic mapping and a candidate-gene approach identified a frameshift mutation in the ALLENE OXIDE SYNTHASE...

  16. Self healing of defected graphene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jianhui; Shi, Tuwan; Cai, Tuocheng; Wu, Xiaosong; Yu, Dapeng [School of Physics, Peking University, Beijing 100871 (China); State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, Peking University, Beijing 100871 (China); Xu, Tao; Sun, Litao [SEU-FEI Nano-Pico Center, Key Laboratory of MEMS of Ministry of Education, Southeast University, Nanjing 210096 (China)

    2013-03-11

    For electronics applications, defects in graphene are usually undesirable because of their ability to scatter charge carriers, thereby reduce the carrier mobility. It would be extremely useful if the damage can be repaired. In this work, we employ Raman spectroscopy, X-ray photoemission spectroscopy, transmission electron microscopy, and electrical measurements to study defects in graphene introduced by argon plasma bombardment. We have found that majority of these defects can be cured by a simple thermal annealing process. The self-healing is attributed to recombination of mobile carbon adatoms with vacancies. With increasing level of plasma induced damage, the self-healing becomes less effective.

  17. DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects

    OpenAIRE

    K Kessler; Wunderlich, I.; Uebe, S; Falk, N.S.; Giessl, A; Brandstatter, J.H.; Popp, B.; Klinger, P; Ekici, A B; Sticht, H.; Dorr, H. G.; Reis, A; Roepman, R; Seemanova, E; Thiel, C T

    2015-01-01

    Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we perfor...

  18. Genetics of T Cell Defects in Lupus

    Institute of Scientific and Technical Information of China (English)

    Yifang Chen; Laurence More

    2005-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies that cause damage to multiple organs and tissues. Intrinsic defects have been demonstrated in the lymphoid and myeloid cellular compartments, including T cells. Lupus susceptibility is mediated through the interplay of a large number of genes, most of which are still unidentified. Most of the genetic studies in both human patients and mouse models have addressed lupus susceptibility as a whole. More recently however, more attention has been paid to the inheritance of specific lupus-associated phenotypes. In this review, we summarized our results obtained with the Slel locus in the NZM2410 mouse model, which mediates the generation of anti-histone autoreactive T cells. Sle1,which is constituted of multiple genes, is the only known genomic region that is sufficient for the generation of autoreactive T cells. The identification of the corresponding genes will constitute a landmark for our understanding of the mechanisms of autoimmunity. Our results are discussed in the context of candidate genes and the role of T cells in systemic autoimmunity.

  19. Repair of full-thickness meniscal defect with human insulin-like growth factor Ⅰ gene-enhanced tissue engineering%人胰岛素样生长因子Ⅰ基因增强组织工程修复全层半月板缺损

    Institute of Scientific and Technical Information of China (English)

    张海宁; 王英振; 吕成昱; 周峰; 续宗耀

    2013-01-01

    目的 建立全层无血运区半月板缺损模型,观察人胰岛素样生长因子Ⅰ (human insulin-like growth factor Ⅰ,hIGF-Ⅰ)基因修饰骨髓间充质干细胞(bone-marrow mesenchymal stem cells,BMSCs)复合可注射藻酸钙凝胶修复半月板缺损的效果. 方法 制造成年山羊半月板前角无血运区全层缺损模型.实验分为四组,即基因增强组织工程(gene-enhanced tissue engineering,GETE)组(GETE组):用hIGF-Ⅰ基因转染的BMSCs复合可注射藻酸钙凝胶修复半月板缺损;BMSCs组:用BMSCs复合藻酸钙凝胶修复缺损;空载体组:用藻酸钙凝胶空载体修复缺损;对照组:缺损旷置,不做任何修复.术后4,8,16周时相点行大体观察;光镜、电镜观察修复组织变化;测定修复组织中蛋白聚糖含量. 结果 GETE组修复半月板缺损在4~ 16周效果逐渐改善,缺损完全被修复组织填充,色白质韧,结合紧密,与正常半月板组织相似,大体观察优于其他各组;光镜下可见细胞随凝胶纤维排列分布,载体纤维间隙大多为细胞分泌基质所充填,细胞排列密集,基质分布均匀;扫描电镜观察到纤维排列规整紧密,纤维间缝隙为致密的细胞外基质填充;修复组织中蛋白聚糖含量较高,但与正常半月板仍有差异. 结论 转染hIGF-Ⅰ基因的BMSCs复合可注射藻酸钙凝胶可改善全层半月板缺损的修复效果.%Objective To establish a model of full-thickness avascular meniscal defect to assess outcome of bone-marrow mesenchymal stem cells (BMSCs) modified with human insulin-like growth factor Ⅰ (hIGF-Ⅰ) gene and compounded with injectable calcium alginate gel in repair of meniscal defect.Methods Models of full-thickness defect were created in the anterior comer of meniscus in goats,an area lacking of blood supply.The trial categorized the models to four groups:gene-ehanced tissue engineering (GETE) group (hIGF-Ⅰ transfected BMSCs were mixed with calcium alginate gel

  20. Congenital Heart Defects (For Parents)

    Science.gov (United States)

    ... defect often appear bluish. Total Anomalous Pulmonary Venous Connection The pulmonary veins normally are the blood vessels ... a long, thin tube called a catheter is threaded through blood vessels in the navel (in a ...

  1. Ordered and Disordered Defect Chaos

    CERN Document Server

    Granzow, G D; Granzow, Glen D.; Riecke, Hermann

    1997-01-01

    Defect-chaos is studied numerically in coupled Ginzburg-Landau equations for parametrically driven waves. The motion of the defects is traced in detail yielding their life-times, annihilation partners, and distances traveled. In a regime in which in the one-dimensional case the chaotic dynamics is due to double phase slips, the two-dimensional system exhibits a strongly ordered stripe pattern. When the parity-breaking instability to traveling waves is approached this order vanishes and the correlation function decays rapidly. In the ordered regime the defects have a typical life-time, whereas in the disordered regime the life-time distribution is exponential. The probability of large defect loops is substantially larger in the disordered regime.

  2. Congenital heart defect corrective surgeries

    Science.gov (United States)

    ... open Arrhythmias Atrial septal defect (ASD) Breathing difficulty Cardiac catheterization Cardiovascular Coarctation of the aorta Congenital heart disease Heart failure - overview Heart transplant Hypoplastic left heart syndrome Patent ductus arteriosus Pediatric ...

  3. Painless causality in defect calculations

    CERN Document Server

    Cheung, C; Cheung, Charlotte; Magueijo, Joao

    1997-01-01

    Topological defects must respect causality, a statement leading to restrictive constraints on the power spectrum of the total cosmological perturbations they induce. Causality constraints have for long been known to require the presence of an under-density in the surrounding matter compensating the defect network on large scales. This so-called compensation can never be neglected and significantly complicates calculations in defect scenarios, eg. computing cosmic microwave background fluctuations. A quick and dirty way to implement the compensation are the so-called compensation fudge factors. Here we derive the complete photon-baryon-CDM backreaction effects in defect scenarios. The fudge factor comes out as an algebraic identity and so we drop the negative qualifier ``fudge''. The compensation scale is computed and physically interpreted. Secondary backreaction effects exist, and neglecting them constitutes the well-defined approximation scheme within which one should consider compensation factor calculatio...

  4. Nucleation of point defect agglomerates

    International Nuclear Information System (INIS)

    A theory of the agglomeration of point defects into dislocation loops and voids is formulated. A critical comparison between theory and experiment is made for nickel and copper irradiated in a high voltage electron microscope

  5. Birth Defects Data and Statistics

    Science.gov (United States)

    ... About Us Information For... Media Policy Makers Data & Statistics Language: English Español (Spanish) Recommend on Facebook Tweet ... and critical. Read below for the latest national statistics on the occurrence of birth defects in the ...

  6. Defects in semiconductors

    International Nuclear Information System (INIS)

    In this thesis, experimental results of the transition metals Ti, V, Nb, Mo, and W as impurity centres in silicon are presented. Transition metal doping was accomplished by ion implantation. Emphasis is put on energy level position, electrical and optical properties of the encountered defect levels. Junction space charge methods (JSCM) such as DLTS, photocapacitance and photocurrent techniques are employed. Three energy levels are found for the 3d-transition metals Ti(Ec-0.06eV, Ec-0.30eV, Ev+0.26) and V(Ec-0.21eV, Ec-0,48e, Ev+0.36eV), and for the 4d-element Nb(Ec-0.29eV, Ec-0.58eV, Ev+0.163eV) in Silicon, whereas only one transition metal induced level is found for Mo(Ev+0.30eV) and W(Ev+0.38eV) respectively. Electrical and optical characteristics of Si1-xGex,0.77cm-2. The solvent Bi, used in the LPE-process, is found to be the dominant impurity element. Furthermore, liquid phase epitaxy of high purity In0.53Ga0.57As on InP, together with the properties of the Cu-induced acceptor in this material are examined. Free electron concentrations of n=5x1014cm-3 and electron Hall-mobilities of μ77K = 44000 cm2/Vs are achieved. The energy level position of the Cu-acceptor is found to be Ev+0.025eV. Photoluminescence and Hall-effect measurements, together with JSCM are the main characterization methods used. The band linups of In0.53Ga0.47As with GaAs and with InP are determined according to the Cu-acceptor energy level position in these materials. Additionally, the hydrostatic pressure dependence of the Cu-acceptor energy level position in In0.53Ga0.47As is examined. (103 refs.)

  7. Mice Null for Sox18 Are Viable and Display a Mild Coat Defect

    OpenAIRE

    Pennisi, David; Bowles, Josephine; Nagy, Andras; Muscat, George; Koopman, Peter

    2000-01-01

    We have previously shown that Sox18 is expressed in developing vascular endothelium and hair follicles during mouse embryogenesis and that point mutations in Sox18 are the underlying cause of cardiovascular and hair follicle defects in ragged (Ra) mice. Here we describe the analysis of Sox18−/− mice produced by gene targeting. Despite the profound defects seen in Ra mice, Sox18−/− mice have no obvious cardiovascular defects and only a mild coat defect with a reduced proportion of zigzag hairs...

  8. Hereditary optic neuropathies share a common mitochondrial coupling defect.

    Science.gov (United States)

    Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naïg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélène; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal

    2008-06-01

    Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.

  9. Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

    Directory of Open Access Journals (Sweden)

    Larsen Lars E

    2010-01-01

    Full Text Available Abstract Background Myxoma virus is a member of the Poxviridae and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy. Results An unusually large number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed that a high proportion of these viral DNA preparations contained a frame-shift mutation within the M135R gene that has previously been identified as a virulence factor. This frame-shift mutation results in expression of a greatly truncated product. The same frame-shift mutation has also been found recently within an avirulent strain of myxoma virus (6918. However, three other frame-shift mutations found in this strain (in the genes M009L, M036L and M148R were not shared with the Danish viruses but a single nucleotide deletion in the M138R/M139R intergenic region was a common feature. Conclusions It appears that expression of the full-length myxoma virus M135R protein is not required for virulence in rabbits. Hence, the frame-shift mutation in the M135R gene in the nonpathogenic 6918 virus strain is not sufficient to explain the attenuation of this myxoma virus but one/some of the other frame-shift mutations alone or in conjunction with one/some of the thirty two amino acid substitutions must also contribute. The real time PCR assay for myxoma virus is a useful diagnostic tool for laboratory confirmation of suspected cases of myxomatosis.

  10. Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

    OpenAIRE

    Larsen Lars E; Breum Solvej Ø; Polacek Charlotta; Belsham Graham J; Bøtner Anette

    2010-01-01

    Abstract Background Myxoma virus is a member of the Poxviridae and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy. Results An unusually large number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over ...

  11. Intrauterine Infections and Birth Defects

    Institute of Scientific and Technical Information of China (English)

    XIAO-YING ZHENG; XIN-MING SONG; LI-HUA PANG; YING JI; HONG-MEI SUN; LEI ZHANG; JU-FEN LIU; YAN-LING GUO; YAN ZHANG; TING ZHANG; YI-FEI WANG; CHEN XU; GONG CHEN; RUOLEI XIN; JIA-PENG CHEN; XU-MEI HU; QING YANG

    2004-01-01

    Intrauterine infection is an important cause of some birth defects worldwide. The most common pathogens include rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. General information about these pathogens in epidemiology, consequence of birth defects, and the possible mechanisms in the progress of birth defects, and the interventions to prevent or treat these pathogens' infections are described. The infections caused by rubella virus, cytomegaloviurs, ureaplasma urealyticum, toxoplasma, etc. are common, yet they are proved to be fatal during the pregnant period, especially during the first trimester. These infections may cause sterility, abortion, stillbirth, low birth weight, and affect multiple organs that may induce loss of hearing and vision, even fetal deformity and the long-term effects. These pathogens' infections may influence the microenvironment of placenta, including levels of enzymes and cytokines, and affect chondriosome that may induce the progress of birth defect. Early diagnosis of infections during pregnancy should be strengthened. There are still many things to be settled, such as the molecular mechanisms of birth defects, the effective vaccines to certain pathogens. Birth defect researches in terms of etiology and the development of applicable and sensitive pathogen detection technology and methods are imperative.

  12. Topological Defects from the Multiverse

    CERN Document Server

    Zhang, Jun; Garriga, Jaume; Vilenkin, Alexander

    2015-01-01

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly e...

  13. Topological defects from the multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jun [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States); Blanco-Pillado, Jose J. [Department of Theoretical Physics, University of the Basque Country UPV/EHU, 48080 Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, 48013, Bilbao (Spain); Garriga, Jaume [Departament de Fisica Fonamental i Institut de Ciencies del Cosmos, Universitat de Barcelona, Marti i Franques, 1, 08028, Barcelona (Spain); Vilenkin, Alexander [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States)

    2015-05-28

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly enhanced in the case where the cosmological constant of our parent vacuum is much higher than the vacuum energy density during inflation in our bubble.

  14. Electrical fingerprint of pipeline defects

    Energy Technology Data Exchange (ETDEWEB)

    Mica, Isabella [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy)]. E-mail: isabella.mica@st.com; Polignano, Maria Luisa [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy); Marco, Cinzia De [STMicroelectronics Srl, via C.Olivetti 2, 20041 Agrate Brianza (Italy)

    2004-12-15

    Pipeline defects are dislocations that connect the source region of the transistor with the drain region. They were widely reported to occur in CMOS, BiCMOS devices and recently in SOI technologies. They can reduce device yield either by affecting the devices functionality or by increasing the current consumption under stand-by conditions. In this work the electrical fingerprint of these dislocations is studied, its purpose is to enable us to identify these defects as the ones responsible for device failure. It is shown that the pipeline defects are responsible for a leakage current from source to drain in the transistors. This leakage has a resistive characteristic and it is lightly modulated by the body bias. It is not sensitive to temperature; vice versa the off-current of a good transistor exhibits the well-known exponential dependence on 1/T. The emission spectrum of these defects was studied and compared with the spectrum of a good transistor. The paper aims to show that the spectrum of a defective transistor is quite peculiar; it shows well defined peaks, whereas the spectrum of a good transistor under saturation conditions is characterized by a broad spectral light emission distribution. Finally the deep-level transient spectroscopy (DLTS) is tried on defective diodes.

  15. Defects formation and wave emitting from defects in excitable media

    Science.gov (United States)

    Ma, Jun; Xu, Ying; Tang, Jun; Wang, Chunni

    2016-05-01

    Abnormal electrical activities in neuronal system could be associated with some neuronal diseases. Indeed, external forcing can cause breakdown even collapse in nervous system under appropriate condition. The excitable media sometimes could be described by neuronal network with different topologies. The collective behaviors of neurons can show complex spatiotemporal dynamical properties and spatial distribution for electrical activities due to self-organization even from the regulating from central nervous system. Defects in the nervous system can emit continuous waves or pulses, and pacemaker-like source is generated to perturb the normal signal propagation in nervous system. How these defects are developed? In this paper, a network of neurons is designed in two-dimensional square array with nearest-neighbor connection type; the formation mechanism of defects is investigated by detecting the wave propagation induced by external forcing. It is found that defects could be induced under external periodical forcing under the boundary, and then the wave emitted from the defects can keep balance with the waves excited from external forcing.

  16. Defect solitons supported by parity-time symmetric defects in superlattices

    Institute of Scientific and Technical Information of China (English)

    Hu Su-Mei; Hu Wei

    2013-01-01

    The existence and stability of defect solitons supported by parity-time (PT) symmetric defects in supedattices are investigated.In the semi-infinite gap,in-phase solitons are found to exist stably for positive defects,zero defects,and negative defects.In the first gap,out-of-phase solitons are stable for positive defects or zero defects,whereas in-phase solitons are stable for negative defects.For both the in-phase and out-of-phase solitons with the positive defect and inphase solitons with negative defect in the first gap,there exists a cutoff point of the propagation constant below which the defect solitons vanish.The value of the cutoff point depends on the depth of defect and the imaginary parts of the PT symmetric defect potentials.The influence of the imaginary part of the PT symmetric defect potentials on soliton stability is revealed.

  17. Construction and testing of a novel host-range defective myxoma virus vaccine with the M063 gene inactivated that is non-permissive for replication in rabbit cells

    OpenAIRE

    Adams, Mathew; Van Leeuwen, Barbara; McFadden, Grant; Kerr, Peter

    2008-01-01

    Deletion of the M063 gene from myxoma virus produces a virus that is unable to replicate in rabbit cells in vitro or in live rabbits but can be propagated in non-rabbit cell lines. A targeted M063 deletion mutant was constructed in the attenuated Uriarra strain of myxoma virus and the ability of this virus to act as a safe, non-transmissible vaccine against myxomatosis was tested in outbred laboratory rabbits. Immunization with the M063 deletion vaccine provided good short-term protection aga...

  18. Construction and testing of a novel host-range defective myxoma virus vaccine with the M063 gene inactivated that is non-permissive for replication in rabbit cells.

    Science.gov (United States)

    Adams, Mathew M; van Leeuwen, Barbara H; McFadden, Grant; Kerr, Peter J

    2008-01-01

    Deletion of the M063 gene from myxoma virus produces a virus that is unable to replicate in rabbit cells in vitro or in live rabbits but can be propagated in non-rabbit cell lines. A targeted M063 deletion mutant was constructed in the attenuated Uriarra strain of myxoma virus and the ability of this virus to act as a safe, non-transmissible vaccine against myxomatosis was tested in outbred laboratory rabbits. Immunization with the M063 deletion vaccine provided good short-term protection against lethal challenge with virulent myxoma virus. Long-term protection was similar to reported results with heterologous live virus, with some rabbits protected but others succumbing to challenge. Replication-deficient poxvirus vaccines, like the Modified Vaccinia Virus Ankara (MVA) in man and the myxoma virus vaccine described here in rabbits, are very attractive from a safety perspective. Seasonal boosting would be predicted to provide long-term protection. Targeted host-range gene deletions could have potential for rapid development of poxvirus vaccines in general. PMID:18778680

  19. Defects in conformal field theory

    Science.gov (United States)

    Billò, Marco; Gonçalves, Vasco; Lauria, Edoardo; Meineri, Marco

    2016-04-01

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the displacement operator, which appears among the contact terms, to the reflection coefficient of a conformal interface, and we find unitarity bounds for the latter.

  20. Defects in conformal field theory

    CERN Document Server

    Billò, Marco; Lauria, Edoardo; Meineri, Marco

    2016-01-01

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the ...

  1. Stoichiometric Defects in Silicon Carbide

    International Nuclear Information System (INIS)

    Defect structures showing odd-membered rings are known features of several tetrahedral semiconductors as well as carbon nano-structures; examples of them are bond defects in crystalline and amorphous silicon, Stone Wales defects in fullerenes and carbon nano-tubes, and the core structure of partial dislocations in some tetrahedral semiconductors. We investigate, using Density Functional Theory, two types of stoichiometry-conserving defects, which we call SCD and anti-SCD and which are metastable structures presenting five- and seven-membered rings, both in the cubic and in the hexagonal 4H-SiC polytypes. We also investigate the annealing properties of the two mentioned variants and find that one of them (SCD) easily disappears, turning back to a normal site, while the other (anti-SCD) transforms to an antisite pair, overcoming a barrier of 0. 21 eV. The very short lifetimes at ambient conditions explain why those defects have not been observed up to now, but they suggest they should be observable at very low temperature, and we provide local vibrational modes to facilitate their identification. (authors)

  2. Neural Tube Defects, Folic Acid and Methylation

    Directory of Open Access Journals (Sweden)

    Henk J. Blom

    2013-09-01

    Full Text Available Neural tube defects (NTDs are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

  3. Distribution of Topological Defects on Axisymmetric Surface

    Institute of Scientific and Technical Information of China (English)

    SI Tie-Yan; DUAN Yi-Shi

    2006-01-01

    We propose a general method of determining the distribution of topological defects on axisymmetric surface,and study the distribution of topological defects on biconcave-discoid surface, which is the geometric configuration of red blood cell. There are three most possible cases of the distribution of the topological defects on the biconcave surface:four defects charged with 1/2, two defects charged with +1, or one defect charged with 2. For the four defect charged with 1/2, they sit at the vertices of a square imbedded in the equator of biconcave surface.

  4. Defect Management in Agile Software Development

    Directory of Open Access Journals (Sweden)

    Rida Noor

    2014-03-01

    Full Text Available Agile development reduces the risk of developing low quality software in the first place by minimizing defects. In agile software development formal defect management processes help to build quality software. The core purpose of defect management is to make the software more effective and efficient in order to increase its quality. There are several methods for handling defects like defect prevention, defect discovery and resolution which are used by software developers and testers. Refactoring keeps the system clean by identifying and removing quality defects. To gain the full confidence of the customer defect management should be involved at every stage of development. Agile methodologies focus on delivering the software in form of short iterations. Thus each iteration helps to overcome defects and leads better development and end user satisfaction. This study paints the picture of handling the software defects using agile based Software Development Process.

  5. Vaccine Design: Replication-Defective Adenovirus Vectors.

    Science.gov (United States)

    Zhou, Xiangyang; Xiang, Zhiquan; Ertl, Hildegund C J

    2016-01-01

    Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies. PMID:27076309

  6. Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

    DEFF Research Database (Denmark)

    Belsham, Graham; Polacek, Charlotta; Breum, Solvej Østergaard;

    2010-01-01

    number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed......Background: Myxoma virus is a member of the Poxviridae and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy. Results: An unusually large......-shift mutations alone or in conjunction with one/some of the thirty two amino acid substitutions must also contribute. The real time PCR assay for myxoma virus is a useful diagnostic tool for laboratory confirmation of suspected cases of myxomatosis....

  7. Absence of steroid biosynthetic defects in heterozygote individuals for classic 11{beta}-hydroxylase deficiency due to a R448H mutation in the CYP11B1 gene

    Energy Technology Data Exchange (ETDEWEB)

    Roesler, A.; Cohen, H. [Hadassah-Hebrew Univ. Medical Center, Jerusalem (Israel)

    1995-12-01

    Steroid 11{beta}-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) is responsible for less than 5% of cases of classic congenital adrenal hyperplasia, but it is relatively frequent in Israel, among Jews of Moroccan origin. Affected individuals have a single base substitution in exon 8 of CYP11B1 gene, codon 448, from CGC (arginine) to CAC (histidine) (R448H), a mutation that abolishes enzyme activity completely. We studied the hormonal response to ACTH stimulation in individuals genotyped to have the R448H mutation in one allele only (heterozygotes), and who were therefore assumed to have 50% of 11{beta}-hydroxylase activity. No demonstrable hormonal abnormalities were found in the 6 adults (3 mothers and 3 fathers) and 2 sons studied, suggesting that a quantitatively reduced 11{beta}-hydroxylase is still enough for normal adrenal biosynthesis. 19 refs., 1 fig., 2 tabs.

  8. Theory of Defects in Semiconductors

    CERN Document Server

    Drabold, David A

    2007-01-01

    Semiconductor science and technology is the art of defect engineering. The theoretical modeling of defects has improved dramatically over the past decade. These tools are now applied to a wide range of materials issues: quantum dots, buckyballs, spintronics, interfaces, amorphous systems, and many others. This volume presents a coherent and detailed description of the field, and brings together leaders in theoretical research. Today's state-of-the-art, as well as tomorrow’s tools, are discussed: the supercell-pseudopotential method, the GW formalism,Quantum Monte Carlo, learn-on-the-fly molecular dynamics, finite-temperature treatments, etc. A wealth of applications are included, from point defects to wafer bonding or the propagation of dislocation.

  9. Photonic crystals with topological defects

    CERN Document Server

    Liew, Seng Fatt; Xiong, Wen; Cao, Hui

    2014-01-01

    We introduce topological defect to a square lattice of elliptical cylinders. Despite the broken translational symmetry, the long-range positional order of the cylinders leads to residual photonic bandgap in the density of optical states. However, the band-edge modes are strongly modified by the spatial variation of ellipse orientation. The $\\Gamma-X$ band-edge mode splits into four regions of high intensity and the output flux becomes asymmetric due to the formation of crystalline domains with different orientation. The $\\Gamma-M$ band-edge mode has the energy flux circulates around the topological defect center, creating an optical vortex. By removing the elliptical cylinders at the center, we create localized defect states which are dominated by either clockwise or counter-clockwise circulating waves. The flow direction can be switched by changing the ellipse orientation. The deterministic aperiodic variation of the unit cell orientation adds another dimension to the control of light in photonic crystals, e...

  10. Surface defects as transfer matrices

    CERN Document Server

    Maruyoshi, Kazunobu

    2016-01-01

    The supersymmetric index of the 4d $\\mathcal{N} = 1$ theory realized by a brane tiling coincides with the partition function of an integrable 2d lattice model. We propose that a class of half-BPS surface defects in brane tiling models are represented on the lattice model side by transfer matrices constructed from L-operators. For the simplest surface defect in theories with $\\mathrm{SU}(2)$ flavor groups, we identify the relevant L-operator as that discovered by Sklyanin in the context of the eight-vertex model. We verify our proposal by computing the indices of class-$\\mathcal{S}$ and -$\\mathcal{S}_k$ theories in the presence of the surface defect.

  11. HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.

    Directory of Open Access Journals (Sweden)

    Angeline S Andrew

    Full Text Available Bladder cancer is the 4(th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62. This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63. The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25 than females (OR 1.56 95%CI 0.83-2.95, (SNP-gender interaction P = 0.048. We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003. The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.

  12. Thoracic skeletal defects and cardiac malformations: a common epigenetic link?

    Science.gov (United States)

    Weston, Andrea D; Ozolins, Terence R S; Brown, Nigel A

    2006-12-01

    Congenital heart defects (CHDs) are the most common birth defects in humans. In addition, cardiac malformations represent the most frequently identified anomaly in teratogenicity experiments with laboratory animals. To explore the mechanisms of these drug-induced defects, we developed a model in which pregnant rats are treated with dimethadione, resulting in a high incidence of heart malformations. Interestingly, these heart defects were accompanied by thoracic skeletal malformations (cleft sternum, fused ribs, extra or missing ribs, and/or wavy ribs), which are characteristic of anterior-posterior (A/P) homeotic transformations and/or disruptions at one or more stages in somite development. A review of other teratogenicity studies suggests that the co-occurrence of these two disparate malformations is not unique to dimethadione, rather it may be a more general phenomenon caused by various structurally unrelated agents. The coexistence of cardiac and thoracic skeletal malformations has also presented clinically, suggesting a mechanistic link between cardiogenesis and skeletal development. Evidence from genetically modified mice reveals that several genes are common to heart development and to formation of the axial skeleton. Some of these genes are important in regulating chromatin architecture, while others are tightly controlled by chromatin-modifying proteins. This review focuses on the role of these epigenetic factors in development of the heart and axial skeleton, and examines the hypothesis that posttranslational modifications of core histones may be altered by some developmental toxicants.

  13. Cell-extrinsic defective lymphocyte development in Lmna(-/- mice.

    Directory of Open Access Journals (Sweden)

    J Scott Hale

    Full Text Available BACKGROUND: Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development. PRINCIPAL FINDINGS: Lmna(-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+ and CD8(+ T cells. Transplantation of Lmna(-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development. CONCLUSIONS: Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.

  14. Atrial – Ventricular Septal Defect

    Directory of Open Access Journals (Sweden)

    T Panagiotopoulos

    2009-05-01

    Full Text Available Atrial and ventricular septal defect constitute the most common congenital heart disease.Aim: Τhe aim of the present retrospective study was to record data and factors that affect atrial and ventricular septal defect.Method and material: The sample study included patients of both sexes who were hospitalized with diagnosis atrial and ventricular septal defect in a Cardiac Surgery hospital of Athens. A specially constructed printed form was used for data collection, where were recorded the demographic and personal variables, the pathological, surgical, cardiology and obstetric history, the habits of adults, as well as the personal characteristics of mothers. Analysis of data was performed by descriptive statistical analysis.Results: The sample study consisted of 101 individuals with diagnosis atrial or ventricular Septal Defect, of which 40% were boys and 60% girls. The 70% of the sample study suffered from atrial Septal Defect and the 30% suffered from ventricular Septal Defect. Regarding age, 12% of the sample study was 0-1 years old, 35% was >1 years old, 8% was >12-18 years old and 45% over than 18 years old. Regarding educational status of the adult participants, 9% was of 0-6 years education, 22%>6 -12 years, 13%>12 years. 14% of the adult paticipants smoked, 4% consumed alcohol and 5% smoked in conjunction with alcohol. In terms of the obstetric history of the sample studied, 32% of the cases had normal birth, 4% had a twin birth and 1% had a triplet one. According to the variables related to mothers, the mean age of the mother was 30 years and 3 months, 10% were smokers at pregnancy and 3% used chemical substance and mainly hair color. Also, the results of the present study showed that individuals of 12-18 and >18 years old did not suffer from ventricular Septal Defect, whereas the infants 0-1 years old did not suffer from Atrial Septal Defect. The mean value of age at the admission in intensive care unit was 7 months (12% for the infants

  15. Alarming Rise In Birth Defects

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A rapid rise in birth defects has prompted China to look for causes and solutionsEvery 60 seconds two children are born in China with a handicap.It’s an alarming fact,but one that young adults across the country who hope to have children face every day. At a conference on the prevention of birth defects in Chengdu of Sichuan Province in September,Vice Minister of the National Population and Family Planning Commission Jiang Fan revealed this inconvenient truth, supported by shocking statistics.

  16. Resonant Production of Topological Defects

    CERN Document Server

    Digal, S; Sen-Gupta, S K; Srivastava, A M; Digal, Sanatan; Ray, Rajarshi; Sengupta, Supratim; Srivastava, Ajit M.

    2000-01-01

    We describe a novel phenomenon in which vortices are produced due to resonant oscillations of a scalar field which is driven by a periodically varying temperature T, with T remaining much below the critical temperature $T_c$. Also, in a rapid heating of a localized region to a temperature {\\it below} $T_c$, far separated vortex and antivortex can form. We compare our results with recent models of defect production during reheating after inflation. We also discuss possible experimental tests of our predictions of topological defect production {\\it without} ever going through a phase transition.

  17. Modify or die? - RNA modification defects in metazoans

    Science.gov (United States)

    Sarin, L Peter; Leidel, Sebastian A

    2014-01-01

    Chemical RNA modifications are present in all kingdoms of life and many of these post-transcriptional modifications are conserved throughout evolution. However, most of the research has been performed on single cell organisms, whereas little is known about how RNA modifications contribute to the development of metazoans. In recent years, the identification of RNA modification genes in genome wide association studies (GWAS) has sparked new interest in previously neglected genes. In this review, we summarize recent findings that connect RNA modification defects and phenotypes in higher eukaryotes. Furthermore, we discuss the implications of aberrant tRNA modification in various human diseases including metabolic defects, mitochondrial dysfunctions, neurological disorders, and cancer. As the molecular mechanisms of these diseases are being elucidated, we will gain first insights into the functions of RNA modifications in higher eukaryotes and finally understand their roles during development. PMID:25692999

  18. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  19. Creating Knockouts of Conserved Oligomeric Golgi Complex Subunits Using CRISPR-Mediated Gene Editing Paired with a Selection Strategy Based on Glycosylation Defects Associated with Impaired COG Complex Function.

    Science.gov (United States)

    Blackburn, Jessica Bailey; Lupashin, Vladimir V

    2016-01-01

    The conserved oligomeric Golgi (COG) complex is a key evolutionally conserved multisubunit protein machinery that regulates tethering and fusion of intra-Golgi transport vesicles. The Golgi apparatus specifically promotes sorting and complex glycosylation of glycoconjugates. Without proper glycosylation and processing, proteins and lipids will be mislocalized and/or have impaired function. The Golgi glycosylation machinery is kept in homeostasis by a careful balance of anterograde and retrograde trafficking to ensure proper localization of the glycosylation enzymes and their substrates. This balance, like other steps of membrane trafficking, is maintained by vesicle trafficking machinery that includes COPI vesicular coat proteins, SNAREs, Rabs, and both coiled-coil and multi-subunit vesicular tethers. The COG complex interacts with other membrane trafficking components and is essential for proper localization of Golgi glycosylation machinery. Here we describe using CRISPR-mediated gene editing coupled with a phenotype-based selection strategy directly linked to the COG complex's role in glycosylation homeostasis to obtain COG complex subunit knockouts (KOs). This has resulted in clonal KOs for each COG subunit in HEK293T cells and gives the ability to further probe the role of the COG complex in Golgi homeostasis. PMID:27632008

  20. The familial hyperchylomicronemia syndrome: New insights into underlying genetic defects

    Energy Technology Data Exchange (ETDEWEB)

    Santamarina-Fojo, S.; Brewer, H.B. (National Inst. of Health, Bethesda, MD (United States))

    1991-02-20

    This case history reports the diagnosis of familial hyperchylomicronemia, a rare genetic syndrome inherited as an autosomal recessive trait. It is characterized by severe fasting hypertriglyceridemia and massive accumulations of chylomicrons in plasma. The two major molecular defects in the disease are a deficiency of lipoprotein lipase or of apo C-II. The location of the mutations in the human apolipoprotein (apo) C-II gene are identified.

  1. Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2/TFIIH.

    NARCIS (Netherlands)

    A.J. van Vuuren (Hanneke); W. Vermeulen (Wim); L. Ma (Libin); G. Weeda (Geert); E. Appeldoorn (Esther); N.G.J. Jaspers (Nicolaas); A.J. van der Eb; J.H.J. Hoeijmakers (Jan); S. Humbert; L. Schaeffer; J-M. Egly (Jean-Marc)

    1994-01-01

    textabstractERCC3 was initially identified as a gene correcting the nucleotide excision repair (NER) defect of xeroderma pigmentosum complementation group B (XP-B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibil

  2. Nuclear Pasta: Topology and Defects

    Science.gov (United States)

    da Silva Schneider, Andre; Horowitz, Charles; Berry, Don; Caplan, Matt; Briggs, Christian

    2015-04-01

    A layer of complex non-uniform phases of matter known as nuclear pasta is expected to exist at the base of the crust of neutron stars. Using large scale molecular dynamics we study the topology of some pasta shapes, the formation of defects and how these may affect properties of neutron star crusts.

  3. Guidance for Preventing Birth Defects

    Science.gov (United States)

    ... healthy during pregnancy, and giving your baby a healthy start in life will help you to have peace of mind. Before pregnancy » During pregnancy » To learn about CDC’s work to help prevent birth defects, visit our Research and Tracking page. Related Links Disability and Health ...

  4. Brane Inflation and Defect Formation

    OpenAIRE

    Davis, A. C.; Brax, P.H.; van de Bruck, C.

    2008-01-01

    Brane inflation and the production of topological defects at the end of the inflationary phase are discussed. After a description of the inflationary setup we discuss the properties of the cosmic strings produced at the end of inflation. Specific examples of brane inflation are described: $D-\\bar D$ inflation, $D3/D7$ inflation and modular inflation

  5. Interaction between epidemiology and laboratory sciences in the study of birth defects: Design of birth defects risk factor surveillance in metropolitan Atlanta

    Energy Technology Data Exchange (ETDEWEB)

    Lynberg, M.C.; Khoury, M.J. (Dept. of Health and Human Services, Atlanta, GA (United States))

    1993-01-01

    Despite years of research, the etiology of most birth defects remains largely unknown. Interview instruments have been the major tools in the search for environmental causes of birth defects. Because of respondents' problems with recognition and recall, interviews are limited in their capacity to measure certain exposures. Laboratory scientists can have a major impact on defining markers of environmental exposure and genetic susceptibility. The Centers for Disease Control is starting a case-control study of serious birth defects on the basis of a population-based surveillance system for birth defects diagnosed during the first year of life in metropolitan Atlanta, Each year, 300 infants with selected birth defects (case subjects) and 100 population-based control subjects (infants without birth defects) will be enrolled in an ongoing study that will supplement surveillance. In addition to conducting extensive maternal interviews, we will collect blood and urine specimens from case and control subjects and their mothers for laboratory testing. Eventually, some environmental sampling may be incorporated. Particular areas of emphasis are (1) nutritional factors, specifically measuring maternal folic acid levels and other micronutrients (e.g., zinc) to explore their role in the etiology of neural tube defects, (2) substance use, specifically measuring cocaine metabolites in the blood and urine to explore their role for specific vascular disruption defects, and (3) environmental factors such as pesticides and aflatoxins, to explore their potential relationships with specific defects. In addition, a DNA bank will be maintained to evaluate the role of specific candidate genes in the etiology of birth defects. The development and testing of these methods could be useful to assess the interaction between environmental exposures and genetic susceptibility in the etiology of birth defects. 15 refs., 1 fig., 1 tab.

  6. Haploinsufficiency of TAB2 Causes Congenital Heart Defects in Humans

    OpenAIRE

    Thienpont, Bernard; Zhang, Litu; Postma, Alex V; Breckpot, Jeroen; Tranchevent, Léon-Charles; Van Loo, Peter; Møllgård, Kjeld; Tommerup, Niels; Bache, Iben; Tümer, Zeynep; van Engelen, Klaartje; Menten, Björn; Mortier, Geert; Waggoner, Darrel; Gewillig, Marc

    2010-01-01

    Congenital heart defects (CHDs) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their etiology remains often obscure. We identified a locus for CHDs on 6q24-q25. Genotype-phenotype correlations in 12 patients carrying a chromosomal deletion on 6q delineated a critical 850 kb region on 6q25.1 harboring five genes. Bioinformatics prioritization of candidate genes in this locus for a role in CHDs identified the TGF-β-activated kinase 1/M...

  7. Casting defects analysis by the Pareto method

    Directory of Open Access Journals (Sweden)

    B. Borowiecki

    2011-07-01

    Full Text Available On the basis of receive results formed of diagram Pareto Lorenz. On the basis of receive graph it affirmed, that for 70% general number casting defects answered 3 defects (9 contribution – 100% defects. For 70% general number defects of influence it has three type of causes: sand holes, porosity and slaginclusions. Thedefects show that it is necessary to take up construction gatingsystem. The remaining 8 causes have been concerned only 25%, with general number of casting defects. Analysis of receive results permit to determine of direction of correct actions in order to eliminate or to limit the most defects.

  8. Genotype-phenotype relationships in human red/green color-vision defects: Molecular and psychophysical studies

    Energy Technology Data Exchange (ETDEWEB)

    Deeb, S.S.; Motulsky, A.G.; Lindsey, D.T.; Hibiya, Y.; Sanocki, E.; Winderickx, J.; Teller, D.Y. (Univ. of Washington, Seattle, WA (United States))

    1992-10-01

    The relationship between the molecular structure of the X-linked red and green visual pigment genes and color-vision phenotype as ascertained by anomaloscopy was studied in 64 color-defective males. The great majority of red-green defects were associated with either the deletion of the green-pigment gene or the formation of 5[prime] red-green hybrid genes or 5[prime] green-red hybrid genes. A rapid PCR-based method allowed detection of hybrid genes, including those undetectable by Southern blot analysis, as well as more precise localization of the fusion points in hybrid genes. Protan color-vision defects appeared always associated with 5[prime] red-green hybrid genes. Carriers of single red-green hybrid genes with fusion in introns 1-4 were protanopes. However, carriers of hybrid genes with red-green fusions in introns 2, 3, or 4 in the presence of additional normal green genes manifested as either protanopes or protanomalous trichromats, with the majority being protanomalous. Deutan defects were associated with green-pigment gene deletions, with 5[prime] green-red hybrid genes, or, rarely, with 5[prime] green-red-green hybrid genes. Complete green-pigment gene deletions or green-red fusions in intron 1 were usually associated with deuteranopia, although the authors unexpectedly found three carriers of a single red-pigment gene without any green-pigment genes to be deuteranomalous trichromats. All but one of the other deuteranomalous subjects had green-red hybrid genes with intron 1, 2, 3, or 4 fusions, as well as several normal green-pigment genes. The one exception had a grossly normal gene array, presumably with a more subtle mutation. Amino acid differences in exon 5 largely determine whether a hybrid gene will be more redlike or more greenlike in phenotype. Various discrepancies as to severity (dichromacy or trichromacy) remain unexplained but may arise because of variability of expression, postreceptoral variation, or both.

  9. Single nucleotide polymorphisms of folate metabolism pathway genes in central chinese families with neural tube defects%华中地区神经管缺陷家庭叶酸代谢相关基因的单核苷酸多态性研究

    Institute of Scientific and Technical Information of China (English)

    刘坚; 戚静; 祝婕; 张李霞; 宁琴; 梁雁; 罗小平

    2010-01-01

    Objective To investigate the contribution of single nucleotide polymorphisms (SNP)variation in folate metabolism pathway genes and its interaction with environmental risk factors to the etiology of NTD. Methods In 275 families from central China, a total of 278 aborted fetal tissues or blood samples were collected from NTD individuals, 478 maternal and/or paternal blood samples were also obtained as controls. Folate supplementation, maternal diabetes mellitus and medication before pregnancy and during the first trimester of pregnancy were investigated. SNP analyses of all samples were performed by CEQ 8800. Case-parent control study and transmission/disequilibrium tests (TDT) were performed according to environmental cofactors stratification to evaluated 28 SNP in 12 folate pathway genes associated with human NTD. Results Only gene MTHFR rs1801133 was significantly associated with NTD, and synergistic effects of environmental risk factors (no folate supplementation and maternal diabetes) were shown on the occurrence of NTD. Linkage disequilibrium between BHMT rs3733890 and NTD existed in case of no folate supplementation,whereas the genotype alone did not contribute to the etiology of NTD. Other SNP were not significantly associated with NTD. Conclusions MTHFR rs1801133 is a risk factor of NTD, but BHMT rs3733890 is not an independent risk factor. Further investigations in folate and methionine cycle genes are requird in larger scale to enclose the interactions between gene and gene, or gene and environmental factors.%目的 通过对叶酸代谢相关基因的单核苷酸多态性(single nucleotide polymorphism,SNP)与环境危险因子交互作用的关联分析,寻找神经管缺陷(neural tube defects,NTD)致病基因及环境危险因素. 方法收集NTD流产胎儿组织标本或患儿血标本(n=278)及其正常双亲的血标本(n=478),记录母亲围孕期补充叶酸、糖尿病、服药史等情况.采用CEQ 8800系统进行多重SNP分析,对所

  10. HEXIM1在先天性心脏病室间隔缺损中的突变及表达研究%Study on the mutation and expression of Hexim1 gene in human ventricular septal defect of congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    王巾; 薛雪; 李辉

    2012-01-01

    目的 通过筛查HEXIM1基因在室间隔缺损(ventricular septal defect,VSD)外周血中的突变和心肌组织中的表达情况,探讨HEXIM1基因与VSD发病机制的关系.方法 采用PCR-DNA测序技术对100例单纯性室间隔缺损的患儿外周血进行基因编码序列突变筛查;以β - actin为内对照,用RT - PCR方法检测HEXIM1基因在14例室间隔缺损引产胎儿中mRNA的表达情况.结果 所有研究对象的HEXIM1基因测序后同GenBank人类HEXIM1编码序列进行比较,有3例患儿(单纯性室间隔缺损)分别存在单核苷酸的多态性(SNP);与正常心肌组织相比,VSD引产胎儿心肌组织中HEXIM1基因mRNA表达呈下降趋势(P<0.05).结论 本实验收集的病例标本中没有发现HEXIM1基因编码区的突变,基因转录水平异常可能是该基因参与VSD形成的一种潜在机制.%Objective; Though screening the mutations of HEXIM1 gene in VSD blood and analyzing the expression levels HEXIM1 gene in the cardiac muscular tissues, we want to approach the relationships between HEXIM1 gene and the pathogenesies in VSD. Method: Screen the mutations of the coding sequences of heximl gene in 100 blood samples from children with simple VSD by PCR method; Using β - actin as internal control, we detected the differential expression between 14 myocardium samples from VSD fetuses and 14 normal controls by reverse transcription polymerase chain reaction (RT - PCR). Results; The entire HEXIM1 coding sequences of all subjects were analyzed and compared with human HEXIM1 coding sequence. NO HEXIM1 mutation was found except for three nucleotide polymorphism (SNP) in three patients with isolated VSD. The mRNA expression levels of HEXIM1 gene show de-scendent tendency in the samples of VSD compared with normal controls. Conclusion: Mutations in coding region of; HEXIM1 gene was not found in our selected simple VSD samples. The abnormality in transcription level of HEXIM1 gene may be a kind of mechanism

  11. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  12. Bacteriophage T4 genes sp and 40 apparently are the same.

    OpenAIRE

    Obringer, J; McCreary, P.; Bernstein, H

    1988-01-01

    The bacteriophage T4 spackle gene, which maintains host membrane integrity, mapped at the same position as gene 40 (head morphogenesis). The cloned spackle gene complemented and cross-reactivated a gene 40 mutant. Like the spackle mutant, gene 40 mutants were defective in genetic exclusion. Apparently, genes spackle and 40 are the same gene.

  13. Cellular Defect May Be Linked to Parkinson's

    Science.gov (United States)

    ... 160862.html Cellular Defect May Be Linked to Parkinson's: Study Abnormality might apply to all forms of ... that may be common to all forms of Parkinson's disease. The defect plays a major role in ...

  14. Expert Network for Die Casing Defect Analysis

    Institute of Scientific and Technical Information of China (English)

    Jiadi WANG; Yongfeng JIANG; Chen LU; Wenjiang DING

    2003-01-01

    Due to the competition and high cost associated with die casting defects, it is urgent to adopt a rapid and effective method for defect analysis. In this research, a novel expert network approach was proposed to avoid some disadvantages of rulebased expert system. The main objective of the system is to assist die casting engineer in identifying defect, determining the probable causes of defect and proposing remedies to eliminate the defect. 14 common die casting defects could be identified quickly by expert system on the basis of their characteristics. BP neural network in combination with expert system was applied to map the complex relationship between causes and defects, and further explained the cause determination process.Cause determination gives due consideration to practical process conditions. Finally, corrective measures were recommended to eliminate the defect and implemented in the sequence of difficulty.

  15. 49 CFR 213.113 - Defective rails.

    Science.gov (United States)

    2010-10-01

    ... head, and extending into or through it. A crack or rust streak may show under the head close to the web... reported as separate defects. (14) Defective weld means a field or plant weld containing...

  16. Charged Semiconductor Defects Structure, Thermodynamics and Diffusion

    CERN Document Server

    Seebauer, Edmund G

    2009-01-01

    The technologically useful properties of a solid often depend upon the types and concentrations of the defects it contains. Not surprisingly, defects in semiconductors have been studied for many years, in many cases with a view towards controlling their behavior through various forms of "defect engineering." For example, in the bulk, charging significantly affects the total concentration of defects that are available to mediate phenomena such as solid-state diffusion. Surface defects play an important role in mediating surface mass transport during high temperature processing steps such as epitaxial film deposition, diffusional smoothing in reflow, and nanostructure formation in memory device fabrication. Charged Semiconductor Defects details the current state of knowledge regarding the properties of the ionized defects that can affect the behavior of advanced transistors, photo-active devices, catalysts, and sensors. Features: Group IV, III-V, and oxide semiconductors; Intrinsic and extrinsic defects; and, P...

  17. Automatic classification of blank substrate defects

    Science.gov (United States)

    Boettiger, Tom; Buck, Peter; Paninjath, Sankaranarayanan; Pereira, Mark; Ronald, Rob; Rost, Dan; Samir, Bhamidipati

    2014-10-01

    Mask preparation stages are crucial in mask manufacturing, since this mask is to later act as a template for considerable number of dies on wafer. Defects on the initial blank substrate, and subsequent cleaned and coated substrates, can have a profound impact on the usability of the finished mask. This emphasizes the need for early and accurate identification of blank substrate defects and the risk they pose to the patterned reticle. While Automatic Defect Classification (ADC) is a well-developed technology for inspection and analysis of defects on patterned wafers and masks in the semiconductors industry, ADC for mask blanks is still in the early stages of adoption and development. Calibre ADC is a powerful analysis tool for fast, accurate, consistent and automatic classification of defects on mask blanks. Accurate, automated classification of mask blanks leads to better usability of blanks by enabling defect avoidance technologies during mask writing. Detailed information on blank defects can help to select appropriate job-decks to be written on the mask by defect avoidance tools [1][4][5]. Smart algorithms separate critical defects from the potentially large number of non-critical defects or false defects detected at various stages during mask blank preparation. Mechanisms used by Calibre ADC to identify and characterize defects include defect location and size, signal polarity (dark, bright) in both transmitted and reflected review images, distinguishing defect signals from background noise in defect images. The Calibre ADC engine then uses a decision tree to translate this information into a defect classification code. Using this automated process improves classification accuracy, repeatability and speed, while avoiding the subjectivity of human judgment compared to the alternative of manual defect classification by trained personnel [2]. This paper focuses on the results from the evaluation of Automatic Defect Classification (ADC) product at MP Mask

  18. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  19. Cooperation and defection in ghetto

    CERN Document Server

    Kulakowski, K

    2006-01-01

    We consider ghetto as a community of people ruled against their will by an external power. Members of the community feel that their laws are broken. However, attempts to leave ghetto makes their situation worse. We discuss the relation of the ghetto inhabitants to the ruling power in context of their needs, organized according to the Maslow hierarchy. Decisions how to satisfy successive needs are undertaken in cooperation with or defection the ruling power. This issue allows to construct the tree of decisions and to adopt the pruning technique from the game theory. Dynamics of decisions can be described within the formalism of fundamental equations. The result is that the strategy of defection is stabilized by the estimated payoff.

  20. Cooperation and Defection in Ghetto

    Science.gov (United States)

    Kułakowski, Krzysztof

    We consider ghetto as a community of people ruled against their will by an external power. Members of the community feel that their laws are broken. However, attempts to leave ghetto makes their situation worse. We discuss the relation of the ghetto inhabitants to the ruling power in context of their needs, organized according to the Maslow hierarchy. Decisions how to satisfy successive needs are undertaken in cooperation with or defection the ruling power. This issue allows to construct the tree of decisions and to adopt the pruning technique from the game theory. Dynamics of decisions can be described within the formalism of fundamental equations. The result is that the strategy of defection is stabilized by the estimated payoff.

  1. Algorithms for defects in nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Chan, T.-L.; Tiago, Murilo L. [Center for Computational Materials, Institute for Computational Engineering and Sciences, University of Texas, Austin, Texas 78712 (United States); Chelikowsky, James R. [Center for Computational Materials, Institute for Computational Engineering and Sciences, University of Texas, Austin, Texas 78712 (United States); Departments of Physics and Chemical Engineering, University of Texas, Austin, Texas 78712 (United States)], E-mail: jrc@ices.utexas.edu

    2007-12-15

    We illustrate recent progress in developing algorithms for solving the Kohn-Sham problem. Key ingredients of our algorithm include pseudopotentials implemented on a real space grid and the use of damped-Chebyshev polynomial filtered subspace iteration. This procedure allows one to predict electronic properties for many materials across the nano-regime, i.e., from atoms to nanocrystals of sufficient size to replicate bulk properties. We will illustrate this method for large silicon quantum dots doped with phosphorus defect.

  2. Roof Defects in North Cyprus

    OpenAIRE

    Aghghaleh, Shadi Pakpour

    2015-01-01

    ABSTRACT: The construction boom in North Cyprus, followed by Annan Plan, have resulted in the construction of a great number of buildings with minimum costs and quality. Although there exist certain rules for the construction of new buildings in North Cyprus, and part of these rules are related to the roofs, defects are observed few years after construction. This thesis intends to introduce different roof systems in North Cyprus, to find their problems and suggest solutions. In this respe...

  3. Semiautomated measurement of pipeline defects

    International Nuclear Information System (INIS)

    The basic technical parameters and properties are given for a newly developed ultrasonic nondestructive testing device for the detection of defects on the inner surface of austenitic tubes of WWER nuclear power plant primary circuits. In addition to the electronic part of the four-channel test equipment, the manipulator and probes have also been designed, and their function is described. The manipulator is designed for measurement on straight pipeline segments of 500 mm inner dia. (B.S.). 4 figs

  4. Electricity Surcharges: Defects and Suggestions

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Since 1980s, the government has decided to levy certain surcharges attached to electricity tariff collected by power grid corporations as government revenue for specific social public welfare purposes. These surcharges presently include the Three Gorges construction fund, urban construction surcharge, rural power grid debt service fund, as well as the newly-added post supporting fund for water reservoirs immigrants and renewable energy surcharge, etc. Yet the legal defects on surcharge policy have brought about operational risks on power grid enterprises.

  5. Detection of Surface Defects on Compact Discs

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Stoustrup, Jakob; Andersen, Palle

    2007-01-01

    Online detection of surface defects on optical discs is of high importance for the accommodation schemes handling these defects. These surface defects introduce fault components to the position measurements of focus and radial tracking positions. The respective controllers will accordingly try to...

  6. 30 CFR 56.7002 - Equipment defects.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Equipment defects. 56.7002 Section 56.7002... Piercing Drilling § 56.7002 Equipment defects. Equipment defects affecting safety shall be corrected before the equipment is used....

  7. 30 CFR 57.7002 - Equipment defects.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Equipment defects. 57.7002 Section 57.7002... Jet Piercing Drilling-Surface Only § 57.7002 Equipment defects. Equipment defects affecting safety shall be corrected before the equipment is used....

  8. A Study of the Genetics and Physical Properties of Dentine Defects

    OpenAIRE

    Mohamed Ibrahim, N. B.

    2013-01-01

    Dentinogenesis Imperfecta (DI) and Dentine Dysplasia (DD) are rare inherited condition affecting the dentine. Previous studies have reported the histological presentation of teeth with dentine defects but the differences between clinical appearances and physical properties, and how do they link to the underlying gene defects, is limited. In addition, the differences between primary and permanent teeth are poorly understood. Aim and Objective: The aim of this study was to investigate if there ...

  9. Effects of prosthesis-bone interface integration of compound double gene transfection rabbit MSCs and collagen/hydroxyl apatite to repair bone defect%双基因转染兔骨髓基质干细胞与胶原/羟基磷灰石复合修复骨缺损及对假体-骨界面整合的影响

    Institute of Scientific and Technical Information of China (English)

    贺金晓; 王英振; 夏长所; 王昌耀; 周瑜; 沐菊; 赫天; 梁晔

    2013-01-01

    体周围新骨形成,提高假体-骨界面骨整合,改善假体稳定性.%Objective To construct prosthesis surrounding bone defect model,forming slow virus mediated BMP-2 and TGF-β3 double gene transfection rabbit MSCs and collagen/hydroxyl apatite complex and implanting to prosthesis around,to investigate the effects of the prosthesis-bone interface bone integration.Methods Longitudinal bone defects were caused between condyle of both femurs of 24 adult clean New Zealand rabbits,male and female unlimited,weight between 2.5 kg and 3.5 kg.Smooth titanium prosthesis were inserted and a bone defect 3 mm wide around prosthesis was preserved.Then the total of 48 defects were divided into 2 groups,each of the experimental group (left)and control group(right) 24 defects.The compression and graft technology was applied to reconstruct bone defects around prosthesis,which were respectively implanted tissue engineering bone,pure collagen/hydroxyl apatite and pressed closely and completely covered implants.Respectively on postoperation 4,8,12 weeks,anesthesia methods were used to put 8 rabbits to death.The general observation,X-ray examination,histomorpbology,histomorphometric and biomechanical examination were applied to evaluation the abilities of using tissue-engineered bone to repair bone defects and effects of osseointegration of the bone-implant interface.Results After 4 weeks,experimental group and the control group,the X-ray was showed there was no significant difference,and mainly collagen/hydroxylapatite high-density shadow around the prosthesis and bone-implant surface bonding strength were respectively 0.3388 ± 0.7206,0.6845 ± 0.7186,the differences was statistically significant (P < 0.01),bone-toimpact contact(BIC) was 0;After eight weeks,X-ray examination was showed that new bone formation was found on the impact surface,for the control group and experimental group,bone-implant surface bonding strength were respectively 0.6468 ±0.7852,1.1824 ± 0

  10. Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells

    Science.gov (United States)

    Hung, Sandy S.C.; Van Bergen, Nicole J.; Jackson, Stacey; Liang, Helena; Mackey, David A.; Hernández, Damián; Lim, Shiang Y.; Hewitt, Alex W.; Trounce, Ian; Pébay, Alice; Wong, Raymond C.B.

    2016-01-01

    Reprogramming of somatic cells into a pluripotent state is known to be accompanied by extensive restructuring of mitochondria and switch in metabolic requirements. Here we utilized Leber's hereditary optic neuropathy (LHON) as a mitochondrial disease model to study the effects of homoplasmic mtDNA mutations and subsequent oxidative phosphorylation (OXPHOS) defects in reprogramming. We obtained fibroblasts from a total of 6 LHON patients and control subjects, and showed a significant defect in complex I respiration in LHON fibroblasts by high-resolution respiratory analysis. Using episomal vector reprogramming, our results indicated that human induced pluripotent stem cell (hiPSC) generation is feasible in LHON fibroblasts. In particular, LHON-specific OXPHOS defects in fibroblasts only caused a mild reduction and did not significantly affect reprogramming efficiency, suggesting that hiPSC reprogramming can tolerate a certain degree of OXPHOS defects. Our results highlighted the induction of genes involved in mitochondrial biogenesis (TFAM, NRF1), mitochondrial fusion (MFN1, MFN2) and glycine production (GCAT) during reprogramming. However, LHON-associated OXPHOS defects did not alter the kinetics or expression levels of these genes during reprogramming. Together, our study provides new insights into the effects of mtDNA mutation and OXPHOS defects in reprogramming and genes associated with various aspects of mitochondrial biology. PMID:27127184

  11. Effects of Stone-Wales and vacancy defects in atomic-scale friction on defective graphite

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiao-Yu [Department of Engineering Mechanics, School of Civil Engineering, Wuhan University, Wuhan 430072 (China); Key Laboratory of Hubei Province for Water Jet Theory and New Technology, Wuhan University, Wuhan 430072 (China); Wu, RunNi; Xia, Re [Key Laboratory of Hubei Province for Water Jet Theory and New Technology, Wuhan University, Wuhan 430072 (China); Chu, Xi-Hua; Xu, Yuan-Jie, E-mail: yj-xu@whu.edu.cn [Department of Engineering Mechanics, School of Civil Engineering, Wuhan University, Wuhan 430072 (China)

    2014-05-05

    Graphite is an excellent solid lubricant for surface coating, but its performance is significantly weakened by the vacancy or Stone-Wales (SW) defect. This study uses molecular dynamics simulations to explore the frictional behavior of a diamond tip sliding over a graphite which contains a single defect or stacked defects. Our results suggest that the friction on defective graphite shows a strong dependence on defect location and type. The 5-7-7-5 structure of SW defect results in an effectively negative slope of friction. For defective graphite containing a defect in the surface, adding a single vacancy in the interior layer will decrease the friction coefficients, while setting a SW defect in the interior layer may increase the friction coefficients. Our obtained results may provide useful information for understanding the atomic-scale friction properties of defective graphite.

  12. Constitutional and thermal defects in UAl4

    International Nuclear Information System (INIS)

    We investigated the point defect structure of oI20 UAl4 in order to study aluminum diffusion. We performed ab initio calculations within a pseudopotentials method implemented in the Vienna Ab initio Simulation Package (VASP) to obtain point defect formation energies: vacancies (VU and VAl ) and antisites (AlU and UAl ). Using a statistical-thermodynamic model we calculated defects concentrations as function of temperature and deviation from stoichiometry. For stoichiometric UAl4, the dominant thermal defects are composed of two antisites. In off-stoichiometric UAl4, antisites are the constitutional defects. For U-rich UAl4, the thermal defect is called interbranch, where one antisite U atom is replaced by five Al vacancies. For Al-rich UAl4, the thermal defect is also an interbranch, where four antisite Al atoms are replaced by five U vacancies

  13. The molecular basis of hereditary enamel defects in humans.

    Science.gov (United States)

    Wright, J T; Carrion, I A; Morris, C

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel.

  14. Developmental defects of the lungs

    Energy Technology Data Exchange (ETDEWEB)

    DaCosta, H.; Pathak, A.; Noronha, O.; Dalal, S.; Shah, K.; Merchant, S.

    1981-06-01

    Poor lung development was first noted on scintigraphy using sup(99m)Tc-phytate in 32 children. They had all been referred for a hepatosplenic scan but the initial circulatory phase of the radiopharmaceutical was also recorded as a routine procedure. In 3 patients it revealed aplasia of an entire lung; bilateral pulmonary hypolplasia was observed in 14 of 16 patients with diaphragmatic herniae. Six patients with congenital heart enlargement showed a poorly developed ipsilateral lung; 5 of 6 patients with dextrocardia without an intracardiac defect had a larger left lung compared with the right lung; both pulmonary beds appeared equal in a patient with mesocardia.

  15. Electronic Defect States in Polyaniline.

    Science.gov (United States)

    Ginder, John Matthew

    The electronic defect states of the conducting polymer polyaniline are studied by a variety of magnetic and optical techniques. The insulating emeraldine base form (EB) of polyaniline can be converted to the conducting emeraldine salt form (ES) by treatment with aqueous acids such as HCl. This "protonic acid doping" process occurs via the bonding of protons to the polymer chain, without altering the number of chain electrons. Magnetic susceptibility studies reveal that a roughly linear growth of the Pauli paramagnetic susceptibility, and an increase in the density of Curie-like spins, accompanies this conversion. Consequently, the protonation-induced defects are mainly spin-1/2 polarons; further, the linear growth of the Pauli susceptibility suggests that fully protonated regions--metallic islands --grow with increasing doping level. The electronic structure of the metallic phase is proposed to be that of a polaron lattice with electronic bandwidth ~0.4 eV and polaron decay length ~2 A. The defects which accomodate excess charge in EB were also studied by near-steady-state photoinduced absorption experiments. Upon photoexcitation into the 2 eV absorption band in EB, several photoinduced features evolved. Induced bleachings of the existing transitions at 2.0 and 3.7 eV were observed; induced absorptions were found at 0.9, 1.4, and 3.0 eV. The 2.0 eV bleaching is consistent with the production of molecular charge-transfer excitons, which may relax to a different ring conformation causing long-lived bleaching, or to two separate charges on a single chain. Indeed, the induced absorptions at 1.4 and 3.0 eV are, by analogy with similar protonation -induced absorptions and by their bimolecular recombination kinetics, assigned to photoexcited polarons. Light-induced electron spin resonance experiments confirm the presence of photogenerated spins upon pumping into the excitonic absorption. Near-steady-state photoconductivity measurements on EB reveal a very small induced

  16. Advanced defect and metrology solutions

    Science.gov (United States)

    Novak, Erik

    2014-05-01

    Cost, weight, performance, and lifetime requirements for precision components used throughout the aerospace and defense industries are driving innovative mechanical designs, manufacturing processes and use of new materials. In turn, these advanced components typically require tighter dimensional and surface tolerances to function as designed. Scratch testers, microscope-based systems, and other traditional metrology systems are inadequate for roughness, small-scale geometry, and defect determination on many of these parts. This talk will examine the advantages and disadvantages of some of the new technologies developed to provide more robust, versatile, and sensitive measurements of precision components for advanced manufacturing environments.

  17. Point defect annealing near voids

    International Nuclear Information System (INIS)

    Kinetic calculations were carried out for the annealing of vacancies and interstitials at voids under irradiation conditions. The case in which there is a small energy barrier between a defect and a void (such as might arise from strain effects or solute segregation at void surfaces) has been investigated in detail. With irradiation conditions which yield void swelling, it is found that a small barrier produces a significant bias parameter for preferential annealing. The bias parameter is relatively insensitive to temperature and irradiation rate, but varies with void radius, decreasing as the void size increases

  18. Improvement in accuracy of defect size measurement by automatic defect classification

    Science.gov (United States)

    Samir, Bhamidipati; Pereira, Mark; Paninjath, Sankaranarayanan; Jeon, Chan-Uk; Chung, Dong-Hoon; Yoon, Gi-Sung; Jung, Hong-Yul

    2015-10-01

    The blank mask defect review process involves detailed analysis of defects observed across a substrate's multiple preparation stages, such as cleaning and resist-coating. The detailed knowledge of these defects plays an important role in the eventual yield obtained by using the blank. Defect knowledge predominantly comprises of details such as the number of defects observed, and their accurate sizes. Mask usability assessment at the start of the preparation process, is crudely based on number of defects. Similarly, defect size gives an idea of eventual wafer defect printability. Furthermore, monitoring defect characteristics, specifically size and shape, aids in obtaining process related information such as cleaning or coating process efficiencies. Blank mask defect review process is largely manual in nature. However, the large number of defects, observed for latest technology nodes with reducing half-pitch sizes; and the associated amount of information, together make the process increasingly inefficient in terms of review time, accuracy and consistency. The usage of additional tools such as CDSEM may be required to further aid the review process resulting in increasing costs. Calibre® MDPAutoClassify™ provides an automated software alternative, in the form of a powerful analysis tool for fast, accurate, consistent and automatic classification of blank defects. Elaborate post-processing algorithms are applied on defect images generated by inspection machines, to extract and report significant defect information such as defect size, affecting defect printability and mask usability. The algorithm's capabilities are challenged by the variety and complexity of defects encountered, in terms of defect nature, size, shape and composition; and the optical phenomena occurring around the defect [1]. This paper mainly focuses on the results from the evaluation of Calibre® MDPAutoClassify™ product. The main objective of this evaluation is to assess the capability of

  19. Experimental Study of the Effect of Intracoronary Stem Cell Infusion on the Isolated Heart Hemodynamics in Mice with Apolipoprotein E Gene Defect%冠状动脉内干细胞灌注对载脂蛋白E基因缺陷小鼠离体心脏血液动力学影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    郑秀峰; 赵石磊; 杨力明

    2015-01-01

    Objective To investigate the effect of intracoronary stem cell infusion on the isolated heart hemodynamics in mice with apolipoprotein E gene defect. Methods Langendorff isolated heart perfusion model was set up. The mice with apolipoprotein E gene defect were equally divided into low-dose group [stem cells perfusion (1.0í106)] and high-dose group [stem cells perfusion (2.5í106)], and the same amount of WT mice were equally divided into low-dose control group[stem cells perfusion (1.0í106)] and high-dose control group[stem cells perfusion(2.5í106)]. The heart hemodynamics was compared between the groups at the time of perfusion, 5min, 15min, and 30min after perfusion. And the heart cells hemodynamics were compared between the groups 5min, 15min, and 30min after injection. Results The heart rate of the four groups was much lower at T1~T4 than at T0 (P<0.05);and the heart rate of high-dose group changed most significantly. After perfusion of stem cells, the levels of LVEDP increased obviously while levels of +dp/dt and -dp/dt decreased significantly in the four groups, and the high-dose group had the biggest increase or decline. Compared with before perfusion of stem cells, after perfusion, the coronary blood flow in the four groups decreased signifi-cantly,P<0.05, and the high-dose group had the biggest decline compared with the other three groups (P<0.05). 30min after perfu-sion, the proportion of cells in transudate reached more than 60%in all the four groups. Conclusion The intracoronary infusion of stem cells adversely affected the heart hemodynamics in mice with apolipoprotein E gene defect, and the greater the infusion dose was, the more significant adverse effects were.%目的:探讨冠状动脉内干细胞灌注对载脂蛋白E基因缺陷小鼠离体心脏血液动力学的影响。方法设计Langendorff离体心脏灌注模型,比较接受低剂量(1.0×106)、高剂量(2.5×106)干细胞灌注时及灌注后5 min、15 min、30 min两组载脂蛋

  20. Defective glycinergic synaptic transmission in zebrafish motility mutants

    Directory of Open Access Journals (Sweden)

    Hiromi Hirata

    2010-01-01

    Full Text Available Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.

  1. Disruption of the folate pathway in zebrafish causes developmental defects

    Directory of Open Access Journals (Sweden)

    Lee Marina S

    2012-04-01

    Full Text Available Abstract Background Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth defects are not well understood. We explore the use of zebrafish as a model system to investigate the role of folate metabolism during development. Results We first identified zebrafish orthologs of 12 human folate metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts supply the embryo with mRNA so that the embryo has an intact folate pathway. To perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX, a potent inhibitor of dihydrofolate reductase (Dhfr an essential enzyme in the folate metabolic pathway. Embryos exposed to high doses of MTX exhibited developmental arrest prior to early segmentation. Lower doses of MTX resulted in embryos with a shortened anterior-posterior axis and cardiac defects: linear heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense morpholino oligonucleotides resulted in embryonic lethality. One function of the folate pathway is to provide essential one-carbon units for dTMP synthesis, a rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However, additional experiments indicate that these embryos have fewer mitotic cells, as assayed with phospho-histone H3 antibodies, and that treated embryos have perturbed cell cycles. Conclusions Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development.

  2. Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects%神经管畸形患儿还原叶酸载体基因和叶酸之间交互作用

    Institute of Scientific and Technical Information of China (English)

    裴丽君; 朱慧萍; 李智文; 张卫; 任爱国; 朱江辉; 李竹

    2005-01-01

    Objective To search the interaction between reduced folate carrier gene ( RFC1 A80G) polymorphism of children with neural tube defects (NTDs) and maternal periconceptional no supplementation of folic acid. The purpose is to provide the epidemiological evidence for finding genetic marker of NTDs. Methods RFC1 (A80G) genotype was detected using PCR-restricted fragment length polymorphism for the blood DNA of 104 trios with NTDs-affected child, and 100 control families with non-malformed control children. The authors investigated the gene-environment interactions between the offspring RFC1 genotype and maternal periconceptional folic acid supplementation through a case-control study. Results It was observed that the offspring with the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to those with the AA genotype (OR=2.56;95%CI=1.04-6.36) in this population under investigation. The risk of mothers who did not take folic acid for having an NTDs-affected infants was 7.69 (95%CI=2.86-21.75). Among the mothers who did not utilize folic acid supplements, the NTDs risk was 3.30 (95%CI=1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR=8.80, 95%CI=2.86-29.82), compared to "offspring with AA or GA genotype" and "maternal folic acid use", the interactive coefficient being 1.45. Conclusion The above findings indicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in Chinese population, and there is a potential gene-nutrient interaction between offspring RFC1 GG genotype and maternal periconceptional intake of folic acid on the risk of NTDs. However,the sample size of this study was limited, a larger sample of population-based study is required to pursue the initial observation.%目的探讨神经管畸形(neural tube defects, NTDs)患

  3. Molecularly Tunable Fluorescent Quantum Defects.

    Science.gov (United States)

    Kwon, Hyejin; Furmanchuk, Al'ona; Kim, Mijin; Meany, Brendan; Guo, Yong; Schatz, George C; Wang, YuHuang

    2016-06-01

    We describe the chemical creation of molecularly tunable fluorescent quantum defects in semiconducting carbon nanotubes through covalently bonded surface functional groups that are themselves nonemitting. By variation of the surface functional groups, the same carbon nanotube crystal is chemically converted to create more than 30 distinct fluorescent nanostructures with unique near-infrared photoluminescence that is molecularly specific, systematically tunable, and significantly brighter than that of the parent semiconductor. This novel exciton-tailoring chemistry readily occurs in aqueous solution and creates functional defects on the sp(2) carbon lattice with highly predictable C-C bonding from virtually any iodine-containing hydrocarbon precursor. Our new ability to control nanostructure excitons through a single surface functional group opens up exciting possibilities for postsynthesis chemical engineering of carbon nanomaterials and suggests that the rational design and creation of a large variety of molecularly tunable quantum emitters-for applications ranging from in vivo bioimaging and chemical sensing to room-temperature single-photon sources-can now be anticipated. PMID:27159413

  4. Cellular processing and nuclear targeting of non-viral gene delivery systems

    NARCIS (Netherlands)

    Aa, M.A.E.M. van der

    2005-01-01

    Gene therapy utilizes genetic material in order to cure patients either by DNA vaccines or by replacement of a defective gene with a normal one. For successful gene therapy certain elements are required: gene delivery systems with low toxicity and immunity, with efficient gene transfer and high gene

  5. Effects of in-cascade defect clustering on near-term defect evolution

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-08-01

    The effects of in-cascade defect clustering on the nature of the subsequent defect population are being studied using stochastic annealing simulations applied to cascades generated in molecular dynamics (MD) simulations. The results of the simulations illustrates the strong influence of the defect configuration existing in the primary damage state on subsequent defect evolution. The large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades have been shown to be significant factors affecting the evolution of the defect distribution. In recent work, the effects of initial cluster sizes appear to be extremely important.

  6. Surface defects and temperature on atomic friction.

    Science.gov (United States)

    Fajardo, O Y; Mazo, J J

    2011-09-01

    We present a theoretical study of the effect of surface defects on atomic friction in the stick-slip dynamical regime of a minimalistic model. We focus on how the presence of defects and temperature change the average properties of the system. We have identified two main mechanisms which modify the mean friction force of the system when defects are considered. As expected, defects change the potential profile locally and thus affect the friction force. But the presence of defects also changes the probability distribution function of the tip slip length and thus the mean friction force. We corroborated both effects for different values of temperature, external load, dragging velocity and damping. We also show a comparison of the effects of surface defects and surface disorder on the dynamics of the system. PMID:21846940

  7. Perception of risk from automobile safety defects.

    Science.gov (United States)

    Slovic, P; MacGregor, D; Kraus, N N

    1987-10-01

    Descriptions of safety engineering defects of the kind that compel automobile manufacturers to initiate a recall campaign were evaluated by individuals on a set of risk characteristic scales that included overall vehicle riskiness, manufacturer's ability to anticipate the defect, importance for vehicle operation, severity of consequences and likelihood of compliance with a recall notice. A factor analysis of the risk characteristics indicated that judgments could be summarized in terms of two composite scales, one representing the uncontrollability of the damage the safety defect might cause and the other representing the foreseeability of the defect by the manufacturer. Motor vehicle defects were found to be highly diverse in terms of the perceived qualities of their risks. Location of individual defects within the factor space was closely associated with perceived riskiness, perceived likelihood of purchasing another car from the same manufacturer, perceived likelihood of compliance with a recall notice, and actual compliance rates. PMID:3675807

  8. Primordial inhomogeneities from massive defects during inflation

    Science.gov (United States)

    Firouzjahi, Hassan; Karami, Asieh; Rostami, Tahereh

    2016-10-01

    We consider the imprints of local massive defects, such as a black hole or a massive monopole, during inflation. The massive defect breaks the background homogeneity. We consider the limit that the physical Schwarzschild radius of the defect is much smaller than the inflationary Hubble radius so a perturbative analysis is allowed. The inhomogeneities induced in scalar and gravitational wave power spectrum are calculated. We obtain the amplitudes of dipole, quadrupole and octupole anisotropies in curvature perturbation power spectrum and identify the relative configuration of the defect to CMB sphere in which large observable dipole asymmetry can be generated. We observe a curious reflection symmetry in which the configuration where the defect is inside the CMB comoving sphere has the same inhomogeneous variance as its mirror configuration where the defect is outside the CMB sphere.

  9. Geometric Defects in Quantum Hall States

    CERN Document Server

    Gromov, Andrey

    2016-01-01

    We describe a geometric (or gravitational) analogue of the Laughlin quasiholes in the fractional quantum Hall states. Analogously to the quasiholes these defects can be constructed by an insertion of an appropriate vertex operator into the conformal block representation of a trial wavefunction, however, unlike the quasiholes these defects are extrinsic and do not correspond to true excitations of the quantum fluid. We construct a wavefunction in the presence of such defects and explain how to assign an electric charge and a spin to each defect, and calculate the adiabatic, non-abelian statistics of the defects. The defects turn out to be equivalent to the genons in that their adiabatic exchange statistics can be described in terms of representations of the mapping class group of an appropriate higher genus Riemann surface. We present a general construction that, in principle, allows to calculate the statistics of $\\mathbb Z_n$ genons for any "parent" topological phase. We illustrate the construction on the ex...

  10. Little String Origin of Surface Defects

    CERN Document Server

    Haouzi, Nathan

    2016-01-01

    We derive the codimension-two defects of 4d $\\mathcal{N} = 4$ Super Yang-Mills (SYM) theory from the (2, 0) little string. The origin of the little string is type IIB theory compactified on an ADE singularity. The defects are D-branes wrapping the 2-cycles of the singularity. We use this construction to make contact with the description of SYM defects due to Gukov and Witten [arXiv:hep-th/0612073]. Furthermore, we derive from a geometric perspective the complete nilpotent orbit classification of codimension-two defects, and the connection to ADE-type Toda CFT. The only data needed to specify the defects is a set of weights of the algebra obeying certain constraints, which we give explicitly. We highlight the differences between the defect classification in the little string theory and its (2, 0) CFT limit.

  11. Primordial inhomogeneities from massive defects during inflation

    CERN Document Server

    Firouzjahi, Hassan; Rostami, Tahereh

    2016-01-01

    We consider the imprints of local massive defects, such as a black hole or a massive monopole, during inflation. The massive defect breaks the background homogeneity. We consider the limit that the physical Schwarzschild radius of the defect is much smaller than the inflationary Hubble radius so a perturbative analysis is allowed. The inhomogeneities induced in scalar and gravitational wave power spectrum are calculated. We obtain the amplitudes of dipole, quadrupole and octupole anisotropies in curvature perturbation power spectrum and identify the relative configuration of the defect to CMB sphere in which large observable dipole asymmetry can be generated. We observe a curious reflection symmetry in which the configuration where the defect is inside the CMB comoving sphere has the same inhomogeneous variance as its mirror configuration where the defect is outside the CMB sphere.

  12. Phosphorous–vacancy–oxygen defects in silicon

    KAUST Repository

    Wang, Hao

    2013-07-30

    Electronic structure calculations employing the hybrid functional approach are used to gain fundamental insight in the interaction of phosphorous with oxygen interstitials and vacancies in silicon. It recently has been proposed, based on a binding energy analysis, that phosphorous–vacancy–oxygen defects may form. In the present study we investigate the stability of this defect as a function of the Fermi energy for the possible charge states. Spin polarization is found to be essential for the charge neutral defect.

  13. Defect interactions within a group of subcascades

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-10-01

    The evolution of the defect distributions within high energy cascades that contain multiple subcascades is studied as a function of temperature for cascades in copper. Low energy cascades generated with molecular dynamics are placed in close proximity to simulate the arrangement of subcascades within a high energy event, then the ALSOME code follows the evolution of the cascade damage during short term annealing. The intersubcascade defect interactions during the annealing stage are found to be minimal. However, no conclusions regarding effects of subcascades on defect production should be drawn until intersubcascade defect interactions during the quenching stage are examined.

  14. 3-dimensional defect TQFTs and their tricategories

    CERN Document Server

    Carqueville, Nils; Schaumann, Gregor

    2016-01-01

    We initiate a systematic study of 3-dimensional `defect' topological quantum field theories, that we introduce as symmetric monoidal functors on stratified and decorated bordisms. For every such functor we construct a tricategory with duals, which is the natural categorification of a pivotal bicategory. This captures the algebraic essence of defect TQFTs, and it gives precise meaning to the fusion of line and surface defects as well as their duality operations. As examples, we discuss how Reshetikhin-Turaev and Turaev-Viro theories embed into our framework, and how they can be extended to defect TQFTs.

  15. Defect studies of H+ implanted niobium

    International Nuclear Information System (INIS)

    Highlights: • Creation of defects in niobium irradiated by 2.5 MeV protons. • Investigation of implantation-induced defects by positron annihilation spectroscopy. • Study of hydrogen attachment to vacancy-like defects in H+-irradiated Nb. • Identification of V + 2H defects as the dominant positron trap. - Abstract: Defects in Nb specimens implanted with H+ ions were investigated using three complementary techniques of positron annihilation spectroscopy: (i) the positron lifetime (LT) measurements employed for identification of defects in implanted specimens, (ii) the coincidence Doppler broadening (CDB) technique used for investigation of chemical surroundings of defects, and (iii) the variable energy positron annihilation spectroscopy (VEPAS) served for defects depth profiling studies. The virgin Nb sample exhibits a single component spectrum with lifetime of 128 ps which testifies that the sample can be considered as a defect-free material. The sample implanted with H+ ions exhibits two additional positron components with lifetimes of 182 and 204 ps. These components were attributed to the implantation-induced vacancies surrounded by two and one hydrogen atom, respectively. The presence of hydrogen attached to vacancies was confirmed also by CDB investigations

  16. Defect reduction through Lean methodology

    Science.gov (United States)

    Purdy, Kathleen; Kindt, Louis; Densmore, Jim; Benson, Craig; Zhou, Nancy; Leonard, John; Whiteside, Cynthia; Nolan, Robert; Shanks, David

    2010-09-01

    Lean manufacturing is a systematic method of identifying and eliminating waste. Use of Lean manufacturing techniques at the IBM photomask manufacturing facility has increased efficiency and productivity of the photomask process. Tools, such as, value stream mapping, 5S and structured problem solving are widely used today. In this paper we describe a step-by-step Lean technique used to systematically decrease defects resulting in reduced material costs, inspection costs and cycle time. The method used consists of an 8-step approach commonly referred to as the 8D problem solving process. This process allowed us to identify both prominent issues as well as more subtle problems requiring in depth investigation. The methodology used is flexible and can be applied to numerous situations. Advantages to Lean methodology are also discussed.

  17. Renyi entropy and conformal defects

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Lorenzo [Humboldt-Univ. Berlin (Germany). Inst. fuer Physik; Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik; Meineri, Marco [Scuola Normale Superiore, Pisa (Italy); Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Istituto Nazionale di Fisica Nucleare, Pisa (Italy); Myers, Robert C. [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Smolkin, Michael [California Univ., Berkely, CA (United States). Center for Theoretical Physics and Department of Physics

    2016-04-18

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  18. Antigravity from a spacetime defect

    CERN Document Server

    Klinkhamer, F R

    2013-01-01

    A nonsingular localized static classical solution is constructed for standard Einstein gravity coupled to an SO(3)\\times SO(3) chiral model of scalars [Skyrme model]. The construction proceeds in three steps. First, an Ansatz is presented for a solution with nontrivial topology of the spacetime manifold. Second, an exact vacuum solution of the reduced field equations is obtained. Third, matter fields are included and a numerical solution is found. This numerical solution has a negative effective mass, meaning that the gravitational force on a distant point mass is repulsive. The origin of the negative effective mass must lie in the surgery needed to create the "defect" from Minkowski spacetime, but this process involves topology change and lies outside the realm of classical Einstein gravity.

  19. Electricity generation from defective tomatoes.

    Science.gov (United States)

    Shrestha, Namita; Fogg, Alex; Wilder, Joseph; Franco, Daniel; Komisar, Simeon; Gadhamshetty, Venkataramana

    2016-12-01

    The United States faces a significant burden in treating 0.61billionkg of defective tomatoes (culls) every year. We present a proof-of-concept for generating electricity from culled tomatoes in microbial-electrochemical systems (MESs). This study delineates impedance behavior of the culled tomatoes in MESs and compares its impedance spectra with that of soluble substrates (dextrose, acetate, and wastewater). A series of AC and DC diagnostic tests have revealed the superior performance of the culled tomatoes compared to the pure substrates. Cyclic voltammetry results have indicated the active role of indigenous, diffusible redox-active pigments in the culled tomatoes on overall electricity production. Electrochemical impedance spectroscopy results have elucidated the role of peel and seed on the oxidation behavior of the culled tomatoes. PMID:27474917

  20. Defect structures in ceramic superconductors

    International Nuclear Information System (INIS)

    The influence of the defect structure on the superconducting properties of high temperature superconductors has been studied experimentally and by computer simulation technique. The relation between defect structure and the superconducting transition temperature, Tc, has been studied in Co-doped YBCO (YBa2Cu3-yCoyO6+x, 0 ≤ y ≤ 0.5), and it has been shown that th model, which has been established to account for the influence of oxygen ordering on Tc in oxygen deficient YBCO (YBa2Cu3O6+x, x 1.85Ce0.15CuO4+x have been carried out in order to elucidate why this material apparently is an electron conductor in the superconducting phase, and not as the other high temperature superconductors, a hole conductor. Structural studies on Pb2Sr2Y1-xCaxCu3O8 (0 ≤ x ≤ 0.5) have been carried out by neutron powder diffraction and it has been shown how the Ca-stoichiometry influence the Cu-valence in the superconducting CuO2-planes. The structural ordering of epitaxial thin films of YBCO and Bi2Sr2CaCu2O8+x deposit on heated substrates of SrTiO3, MgO, LaAlO3 and NdGaO3 has been studied by x-ray diffraction and Rutherford Backscattering spectroscopy, and the structural ordering has been analysed in relation to the superconducting properties. (au) (9 ills., 10 refs.)

  1. Mechanisms of genome instability induced by RNA-processing defects.

    Science.gov (United States)

    Chan, Yujia A; Hieter, Philip; Stirling, Peter C

    2014-06-01

    The role of normal transcription and RNA processing in maintaining genome integrity is becoming increasingly appreciated in organisms ranging from bacteria to humans. Several mutations in RNA biogenesis factors have been implicated in human cancers, but the mechanisms and potential connections to tumor genome instability are not clear. Here, we discuss how RNA-processing defects could destabilize genomes through mutagenic R-loop structures and by altering expression of genes required for genome stability. A compelling body of evidence now suggests that researchers should be directly testing these mechanisms in models of human cancer. PMID:24794811

  2. Detection of a novel arginine vasopression defect by dideoxy fingerprinting

    Energy Technology Data Exchange (ETDEWEB)

    Krishnamani, M.R.S.; Phillips, J.A. III; Copeland, K.C. (Vanderbilt Univ. School of Medicine, Nashville, TN (United States) Univ. of Vermont College of Medicine, Burlington, VT (United States))

    1993-09-01

    Autosomal dominant neurohypophyseal diabetes insipidus is a familial form of diabetes insipidus. This disorder is associated with variable levels of arginine vasopressin (AVP) and diabetes insipidus of varying severity, which responds to exogenous AVP. To determine the molecular basis of autosomal dominant neurohypophyseal diabetes insipidus, the AVP genes of members of a large kindred were analyzed. A new method, called dideoxy fingerprinting, was used to detect an AVP mutation that was characterized by DNA sequencing. The novel defect found changes the last codon of the AVP signal peptide from alanine to threonine, which should perturb cleavage of mature AVP from its precursor protein and inhibit its secretion or action. 18 refs., 3 figs.

  3. Relationship Between Polymorphism of Methylenetetrahydrofolate Dehydrogenase and Congenital Heart Defect

    Institute of Scientific and Technical Information of China (English)

    JUN CHENG; WEN-LI ZHU; JING-JING DAO; SHU-QING LI; YONG LI

    2005-01-01

    Objective To investigate the relationship between G1958A gene polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital heart disease (CHD) in North China. Methods One hundred and ninety-two CHD patients and their parents were included in this study as case group in Liaoning Province by birth defect registration cards, and 124 healthy subjects (age and gender matched) and their parents were simultaneously selected from the same geographic area as control. Their gene polymorphism of MTHFD G1958A locus was examined with PCR-RFLP, and serum folic acid and homocysteine (Hcy) levels were tested with radio-immunoassay and fluorescence polarization immunoassay (FPIA). Results There existed gene polymorphism at MTHFD G1958A locus in healthy subjects living in North China. The percentages of GG, GA, and AA genotype were 57.98%, 35.57%, and 6.45% respectively, and the A allele frequency was 24.23%, which was significantly different from Western population. No difference was observed when comparing genotype distribution and allele frequency between the case and control groups, so was the result from the comparison between genders. The A allele frequency of arterial septal defect patients' mothers (10.87%) was significantly lower than that of controls (28.15%) (P=0.014), with OR=0.31 (95% CI: 0.09-0.84), and no difference in the other subgroups. The percentage of at least one parent carrying A allele in arterial septal defect subgroup (43.48%) was significantly lower than that in controls (69.64%) (P=0.017), with OR=0.34 (95% CI: 0.12-0.92). The analysis of genetic transmission indicated that there was no transmission disequillibrium in CHD nuclear families. Their serum folic acid level was significantly higher than that of controls (P=0.000), and Hcy level of the former was higher than that of the latter with no statistical significance (P>0.05). Serum Hcy and folic acid levels of mothers with gene mutation were lower than those of mothers

  4. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study.

    NARCIS (Netherlands)

    Desrosiers, T.A.; Herring, A.H.; Shapira, S.K.; Hooiveld, M.; Luben, T.J.; Herdt-Losavio, M.L.; Lin, S.; Olshan, A.F.

    2012-01-01

    Objectives: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation

  5. Rag defects and thymic stroma: lessons from animal models

    Directory of Open Access Journals (Sweden)

    Veronica eMarrella

    2014-06-01

    Full Text Available Thymocytes and thymic epithelial cells (TECs cross-talk is essential to support T-cell development and preserve thymic architecture and maturation of TECs and Foxp3+ natural regulatory T (nTreg cells. Accordingly, disruption of thymic lymphostromal cross-talk may have major implications on the thymic mechanisms that govern T cell tolerance. Several genetic defects have been described in humans that affect early stages of T cell development (leading to Severe Combined Immune Deficiency, SCID or late stages in thymocyte maturation (resulting in combined immunodeficiency. Hypomorphic mutations in SCID-causing genes may allow for generation of a limited pool of T lymphocytes with a restricted repertoire. These conditions are often associated with infiltration of peripheral tissues by activated T cells and immune dysregulation, as best exemplified by Omenn syndrome (OS. In this review, we will discuss our recent findings on abnormalities of thymic microenvironment in OS with a special focus of defective maturation of TECs, altered distribution of thymic dendritic cells (DCs and impairment of deletional and non-deletional mechanisms of central tolerance. Here, taking advantage of mouse models of OS and atypical SCID, we will discuss how modifications in stromal compartment impact and shape lymphocyte differentiation, and vice versa how inefficient T cell signalling results in defective stromal maturation. These findings are instrumental to understand the extent to which novel therapeutic strategies should act on thymic stroma to achieve full immune reconstitution.

  6. Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development

    OpenAIRE

    Manthey, Abby L.; Salil A. Lachke; FitzGerald, Paul G.; Mason, Robert W.; Scheiblin, David A.; McDonald, John H.; Duncan, Melinda K.

    2013-01-01

    SIP1 encodes a DNA-binding transcription factor that regulates multiple developmental processes, as highlighted by the pleiotropic defects observed in Mowat-Wilson Syndrome, which results from mutations in this gene. Further, in adults, dysregulated SIP1 expression has been implicated in both cancer and fibrotic diseases, where it functionally links TGFβ signaling to the loss of epithelial cell characteristics and gene expression. In the ocular lens, an epithelial tissue important for vision,...

  7. Simple intrinsic defects in InAs :

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2013-03-01

    This Report presents numerical tables summarizing properties of intrinsic defects in indium arsenide, InAs, as computed by density functional theory using semi-local density functionals, intended for use as reference tables for a defect physics package in device models.

  8. Defect structure of electrodeposited chromium layers

    CERN Document Server

    Marek, T; Vertes, A; El-Sharif, M; McDougall, J; Chisolm, C U

    2000-01-01

    Positron annihilation spectroscopy was applied to study the effects of pre-treatment and composition of substrates on the quality and defect structure of electrodeposited thick chromium coatings. The results show that both parameters are important, and a scenario is proposed why the mechanically polished substrate gives more defective film than the electro polished one.

  9. On varieties with higher osculating defect

    CERN Document Server

    De Poi, Pietro; Ilardi, Giovanna

    2012-01-01

    In this paper, using the method of moving frames, we generalise some of Terracini's results on varieties with tangent defect. In particular, we characterise varieties with higher order osculating defect in terms of Jacobians of higher fundamental forms and moreover we characterise varieties with "small" higher fundamental forms as contained in scrolls.

  10. Microphthalmia with linear skin defects syndrome.

    Science.gov (United States)

    García-Rabasco, Ana; De-Unamuno, Blanca; Martínez, Francisco; Febrer-Bosch, Isabel; Alegre-de-Miquel, Víctor

    2013-01-01

    Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and sclerocornea (MIDAS) syndrome is a rare X-linked-dominant disorder. We present a patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal, but a skewed X-chromosome inactivation pattern (85:15) was observed.

  11. Theoretical spectroscopy of point defects in semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Bockstedte, M. [ETSF, Univerisdad del Pais Vasco UPV/EHU, San Sebastian (Spain); Theor. Festkoerperphysik, Universitaet Erlangen-Nuernberg, Erlangen (Germany); Gali, Adam [Department of Atomic Physics, Budapest University of Technology and Economics, Budapest (Hungary); Marini, A. [ETSF, Universit di a Roma Tor Vergata, Roma (Italy); Rubio, A. [ETSF, Univerisdad del Pais Vasco UPV/EHU, San Sebastian (Spain); Pankratov, O. [Theor. Festkoerperphysik, Universitaet Erlangen-Nuernberg, Erlangen (Germany)

    2008-07-01

    The current theory of point defects in semiconductors is largely based on the density functional theory (DFT) and the local spin density approximation (LSDA). Numerous defect models have been identified with experimental defect centers by predicting quantities related to the defect's electronic structure. However, there are apparent limitations: the position of localized defect levels is affected by the well-known DFT band gap error and the excited states of defects cannot be assessed rigorously. These two fundamental defect properties are accessible via the many body perturbation theory within the GW-approximation and Bethe-Salpeter equation implemented in the program package SELF. We demonstrate the relevance of this approach for the interpretation of optical experiments for well-identified defect centers. As such we considered the carbon vacancy and di-vacancy in SiC. We show that the observed absorption spectra in contrast to the earlier interpretation also involve resonant levels and the ionization of the vacancy in two different charge states. We discuss the origin of the prominent absorption/photo-luminescence line of the di-vacancy, a common compensation center in semi-insulating SiC.

  12. From gene to disease; hypophosphataemic rickets and the PHEX gene

    NARCIS (Netherlands)

    Jansen, M; van Dael, C.M.L.; Verrijn Stuart, A.A.; van der Hout, A.H.; Rump, P.

    2006-01-01

    X-linked hypophosphataemic rickets is associated with mutations in the PHEX gene on the short arm of the X chromosome, encoding a membrane-bound endoprotease which is predominantly expressed in osteoblasts. Defective PHEX function leaves phosphaturic peptides such as FGF23 uncleaved, enabling these

  13. Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage

    Directory of Open Access Journals (Sweden)

    CH Evans

    2009-12-01

    Full Text Available We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2 was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified (“gene activated” tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.

  14. Identification of genetic defects in primary immunodeficiencies by whole exome sequencing

    DEFF Research Database (Denmark)

    Christiansen, Mette; Jensen, Jens Magnus Bernth; Veirum, Jens Erik;

    2014-01-01

    and Illumina HiSeq, SNP and Indels were called and subsequently filtered using Cartagenia software. First, we identified a heterozygous missense, gain of function mutation in the NLRP3 gene along with compound heterozygosity for MPO defect in a 10 months old girl with juvenile psoriasiform dermatitis...

  15. Geodesic defect anchoring on nematic shells.

    Science.gov (United States)

    Mirantsev, Leonid V; Sonnet, André M; Virga, Epifanio G

    2012-08-01

    Nematic shells are colloidal particles coated with nematic liquid crystal molecules, which may freely glide and rotate on the colloid's surface while keeping their long axis on the local tangent plane. Molecular dynamics simulations on a nanoscopic spherical shell indicate that under appropriate adhesion conditions for the molecules on the equator, the equilibrium nematic texture exhibits at each pole a pair of +1/2 defects so close to one another to be treated as one +1 defect. Spirals connect the polar defects, though the continuum limit of the interaction potential would not feature any elastic anisotropy. A molecular averaging justifies an anchoring defect energy that feels the geodesics emanating from the defect. All our observations are explained by such a geodesic anchoring, which vanishes on flat manifolds. PMID:23005713

  16. Online isolation of defects in cellular nanocomputers

    Institute of Scientific and Technical Information of China (English)

    Teijiro Isokawa; Shin'ya Kowada; Ferdinand Peper; Naotake Kamiura; Nobuyuki Matsui

    2007-01-01

    Unreliability will be a major issue for computers built from components at nanometer scales.Thus,it's to be expected that such computers will need a high degree of defect-tolerance to overcome components' defects which have arisen during the process of manufacturing.This paper presents a novel approach to defect-tolerance that is especially geared towards nanocomputers based on asynchronous cellular automata.According to this approach,defective cells are detected and isolated by small configurations that move around randomly in cellular space.These configurations,called random flies,will attach to configurations that are static,which is typical for configurations that contain defective cells.On the other hand,dynamic configurations,like those that conduct computations,will not be isolated from the rest of the cellular space by the random flies,and will be able to continue their operations unaffectedly.

  17. The Doppler peaks from a generic defect

    CERN Document Server

    Magueijo, J

    1996-01-01

    We investigate which of the exotic Doppler peak features found for textures and cosmic strings are generic novelties pertaining to defects. We find that the ``out of phase'' texture signature is an accident. Generic defects, when they generate a secondary peak structure similar to inflation, apply to it an additive shift. It is not necessary for this shift to be ``out of phase''. We also show which factors are responsible for the absence of secondary oscillations found for cosmic strings. Within this general analysis we finally consider the conditions under which topological defects and inflation can be confused. It is argued that only \\Omega=1 inflation and a defect with a horizon size coherence length have a chance to be confused. Any other inflationary or defect model always differ distinctly. (To appear in the proceedings of the XXXIth Moriond meeting, ``Microwave Background Anisotropies'')

  18. Defect and functionalized graphene for supercapacitor electrodes

    Science.gov (United States)

    Taluja, Yogita; SanthiBhushan, Boddepalli; Yadav, Shekhar; Srivastava, Anurag

    2016-10-01

    The structural, electronic and transport properties of defected (single vacancy and double vacancy) and nitrogen functionalized graphene sheets have been analysed within the framework of Density Functional Theory (DFT) and non-equilibrium Green's function (NEGF) formalism for their possible application as supercapacitor electrodes. Formation energy calculations reveal the increasing stability of defect with nitrogen functional doping concentration at its edges. The extracted electronic properties reveal the presence of acceptor-type energy levels at Fermi level in the defected and functionalized sheets. Transport studies portray remarkable increase in electrical conductivity of graphene sheet after the formation of single vacancy defect and its functionalization. Especially, the Single Vacancy Trimerized pyridine-type defect (SVT) configuration has demonstrated superior thermodynamic stability as well as electrical conductance in comparison to all the other configurations.

  19. The role of point defects and defect complexes in silicon device processing. Summary report and papers

    Energy Technology Data Exchange (ETDEWEB)

    Sopori, B.; Tan, T.Y.

    1994-08-01

    This report is the summary of the third workshop on the role of point defects and defect complexes in silicon device processing. The workshop was organized: (1) to discuss recent progress in the material quality produced by photovoltaic Si manufacturers, (2) to foster the understanding of point defect issues in Si device processing, (3) to review the effects of inhomogeneities on large- area solar cell performance, (4) to discuss how to improve Si solar cell processing, and (5) to develop a new understanding of gettering, defect passivation, and defect annihilation. Separate abstract were prepared for the individual papers, for the database.

  20. Defect in photonic crystal with negative index material

    Institute of Scientific and Technical Information of China (English)

    TANG Kang-song; XIANG Yuan-jiang; WEN Shuang-chun

    2006-01-01

    The transmission property of the photonic crystal containing negative index material is analyzed by means of transfer matrix method.It is demonstrated that a defect mode appears in the conventional Bragg gap and the defect mode is sensitive to the position of the defect cell.For the first time to our knowledge we introduce two defects into such a structure and discuss the dependence of the transmission on the interval of the two defect cells.It is found that a wide degenerate defect mode appears in the Bragg gap,and this degenerate defect mode splits into two different defect modes when the two defect cells become closer.

  1. The defective RNAs of Closteroviridae

    Directory of Open Access Journals (Sweden)

    Munir eMawassi

    2013-05-01

    Full Text Available The family Closteroviridae consists of two genera, Closterovirus and Ampelovirus with monopartite genomes transmitted respectively by aphids and mealybugs and the Crinivirus with bipartite genomes transmitted by whiteflies. The Closteroviridae consists of more than thirty virus species, which differ considerably in their phytopathological significance. Some, like Beet yellows virus (BYV and Citrus tristeza virus (CTV were associated for many decades with their respective hosts, sugar beets and citrus. Others, like the grapevine leafroll-associated ampeloviruses 1, and 3 were also associated with their grapevine hosts for long periods; however difficulties in virus isolation hampered their molecular characterization. The majority of the recently identified Closteroviridae were probably associated with their vegetative propagated host plants for long periods and only detected through the considerable advances in dsRNA isolation and sequencing of PCR amplified replicons. Molecular characterization of CTV and several other Closteroviridae revealed that, in addition to genomic and subgenomic RNAs, infected plants contain several different subviral defective RNAs (dRNAs. The roles and biological functions of dRNAs associated with Closteroviridae remain terra incognita.

  2. Muscular ventricular septal defects: A reappraisal of the anatomy

    NARCIS (Netherlands)

    Wenink, A.C.G.; Oppenheimer-Dekker, A.; Moulaert, A.J.

    1979-01-01

    Among 79 autopsy specimens of hearts with an isolated ventricular septal defect, there were 29 cases of muscular defect. Among 60 hearts with complete transposition of the great arteries and a ventricular septal defect, there were 13 cases with a muscular defect. All muscular defects could be classi

  3. Characterization of the structure and chemistry of defects in materials

    International Nuclear Information System (INIS)

    Research programs, presented at the materials research symposium, on defects in materials are presented. Major areas include: point defects, defect aggregates, and ordering; defects in non-metals and semiconductors; atomic resolution imaging of defects; and gain boundaries, interfaces, and layered materials. Individual projects are processed separately for the data bases

  4. Defect annealing in neutron and ion damaged silicon: Influence of defect clusters and doping

    Science.gov (United States)

    Fleming, R. M.; Seager, C. H.; Bielejec, E.; Vizkelethy, G.; Lang, D. V.; Campbell, J. M.

    2010-03-01

    We have explored defect annealing in radiation damaged silicon in a regime characterized by defect clusters and higher doping. Several types of pnp and npn Si bipolar transistors have been irradiated with ions and neutrons, then isochronally annealed from 300 to 600 K to study the evolution of deep level transient spectroscopy (DLTS) defect signatures. Variations in these data with radiation environment, Fermi level, annealing temperature, and doping density have been used to separate the contributions of three dominant defects to the DLTS defect spectra. We find that the normal Si divacancy and a divacancylike defect with similar properties make similar contributions to a DLTS peak normally associated with transitions from the single minus charge state of the divacancy. However the latter defect is clearly associated with the presence of defect clusters. The vacancy-donor center can also contribute to this high temperature DLTS signature, and its relative importance can be quantitatively assessed by varying doping density and the bias applied to the sample p/n junctions during annealing, and also by the observation that another, donor-related defect grows in as this center anneals. The ratio of vacancy-donor and vacancy-oxygen pairs appears to accurately follow that seen in earlier studies of gamma-irradiated Si. Discussions are presented concerning the effects of defect clustering on the structure, appearance, and evolution of the defects we have identified.

  5. Defect-Defect Interaction in Single-Walled Carbon Nanotubes Under Torsional Loading

    Science.gov (United States)

    Huq, Abul M. A.; Bhuiyan, Abuhanif K.; Liao, Kin; Goh, Kheng Lim

    This paper presents an analysis of interactions between a pair of Stone-Wales (SW) defects in a single-walled carbon nanotube (SWCNT) that has been subjected to an external torque. Defect pairs, representing the different combinations of SW defect of A (SW-A) and B (SW-B) modes, were incorporated in SWCNT models of different chirality and diameter and solved using molecular mechanics. Defect-defect interaction was investigated by evaluating the C-C steric interactions in the defect that possesses the highest potential energy, E, as a function of inter-defect distance, D. This study reveals that the deformation of the C-C bond is attributed to bond stretching and bending. In the SW-B defects, there is an additional contributor arising from the dihedral angular deformation. The magnitude of E depends on the type of defect but the profile of the E versus D curve depends on the orientation of the defects. The largest indifference length, D0, beyond which two defects cease to interact, is approximately 30 Å. When the angular displacement of the tube increases two-fold, E increases, but the profile of the E versus D curve is not affected. The sense of rotation affects the magnitude of E but not the profile of the E versus D curve.

  6. Genetic defects in fatty acid beta-oxidation and acyl-CoA dehydrogenases. Molecular pathogenesis and genotype-phenotype relationships

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter; Andresen, Brage S

    2004-01-01

    Mitochondrial fatty acid oxidation deficiencies are due to genetic defects in enzymes of fatty acid beta-oxidation and transport proteins. Genetic defects have been identified in most of the genes where nearly all types of sequence variations (mutation types) have been associated with disease...

  7. Studying post-etching silicon crystal defects on 300mm wafer by automatic defect review AFM

    Science.gov (United States)

    Zandiatashbar, Ardavan; Taylor, Patrick A.; Kim, Byong; Yoo, Young-kook; Lee, Keibock; Jo, Ahjin; Lee, Ju Suk; Cho, Sang-Joon; Park, Sang-il

    2016-03-01

    Single crystal silicon wafers are the fundamental elements of semiconductor manufacturing industry. The wafers produced by Czochralski (CZ) process are very high quality single crystalline materials with known defects that are formed during the crystal growth or modified by further processing. While defects can be unfavorable for yield for some manufactured electrical devices, a group of defects like oxide precipitates can have both positive and negative impacts on the final device. The spatial distribution of these defects may be found by scattering techniques. However, due to limitations of scattering (i.e. light wavelength), many crystal defects are either poorly classified or not detected. Therefore a high throughput and accurate characterization of their shape and dimension is essential for reviewing the defects and proper classification. While scanning electron microscopy (SEM) can provide high resolution twodimensional images, atomic force microscopy (AFM) is essential for obtaining three-dimensional information of the defects of interest (DOI) as it is known to provide the highest vertical resolution among all techniques [1]. However AFM's low throughput, limited tip life, and laborious efforts for locating the DOI have been the limitations of this technique for defect review for 300 mm wafers. To address these limitations of AFM, automatic defect review AFM has been introduced recently [2], and is utilized in this work for studying DOI on 300 mm silicon wafer. In this work, we carefully etched a 300 mm silicon wafer with a gaseous acid in a reducing atmosphere at a temperature and for a sufficient duration to decorate and grow the crystal defects to a size capable of being detected as light scattering defects [3]. The etched defects form a shallow structure and their distribution and relative size are inspected by laser light scattering (LLS). However, several groups of defects couldn't be properly sized by the LLS due to the very shallow depth and low

  8. Platelet rich fibrin in jaw defects

    Science.gov (United States)

    Nica, Diana; Ianes, Emilia; Pricop, Marius

    2016-03-01

    Platelet rich fibrin (PRF) is a tissue product of autologous origin abundant in growth factors, widely used in regenerative procedures. Aim of the study: Evaluation of the regenerative effect of PRF added in the bony defects (after tooth removal or after cystectomy) Material and methods: The comparative nonrandomized study included 22 patients divided into 2 groups. The first group (the test group) included 10 patients where the bony defects were treated without any harvesting material. The second group included 12 patients where the bony defects were filled with PRF. The bony defect design was not critical, with one to two walls missing. After the surgeries, a close clinically monitoring was carried out. The selected cases were investigated using both cone beam computer tomography (CBCT) and radiographic techniques after 10 weeks postoperatively. Results: Faster bone regeneration was observed in the bony defects filled with PRF comparing with the not grafted bony defects. Conclusions: PRF added in the bony defects accelerates the bone regeneration. This simplifies the surgical procedures and decreases the economic costs.

  9. Exploring atomic defects in molybdenum disulphide monolayers

    KAUST Repository

    Hong, Jinhua

    2015-02-19

    Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation of electric and optical properties. Here we present a comprehensive joint experiment-theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 10 13 cm \\'2 is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices.

  10. Geometric defects in quantum Hall states

    Science.gov (United States)

    Gromov, Andrey

    2016-08-01

    We describe a geometric (or gravitational) analog of the Laughlin quasiholes in fractional quantum Hall states. Analogously to the quasiholes, these defects can be constructed by an insertion of an appropriate vertex operator into the conformal block representation of a trial wave function; however, unlike the quasiholes these defects are extrinsic and do not correspond to true excitations of the quantum fluid. We construct a wave function in the presence of such defects and explain how to assign an electric charge and a spin to each defect and calculate the adiabatic, non-Abelian statistics of the defects. The defects turn out to be equivalent to the genons in that their adiabatic exchange statistics can be described in terms of representations of the mapping class group of an appropriate higher genus Riemann surface. We present a general construction that, in principle, makes it possible to calculate the statistics of Zn genons for any "parent" topological phase. We illustrate the construction on the example of the Laughlin state and perform an explicit calculation of the braiding matrices. In addition to non-Abelian statistics, geometric defects possess a universal Abelian overall phase, determined by the gravitational anomaly.

  11. Reduction in Defect Content in ODS Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ritherdon, J.; Jones, A.R.

    2000-02-01

    The work detailed within this report is a continuation of earlier work that was carried out under contract number IDX-SY382V. The earlier work comprised a literature review of the sources and types of defects found principally in Fe-based ODS alloys together with a series of experiments designed to identify defects in ODS Fe{sub 3}Al material and recommend methods of defect reduction. Defects found in the Mechanically Alloyed (MA) ODS Fe{sub 3}Al included regions of incomplete MA, porosity, intrusions and fine-grained stringers. Some defects tended to be found in association with one another e.g. intrusions and fine-grained stringers. Preliminary powder separation experiments were also performed. The scope and objectives of the present work were laid out in the technical proposal ``Reduction in Defect Content in ODS Alloys--II'' which formed the basis of amendment 3 of the current contract. The current studies were devised in the context of the preceding work with a view to extending and concluding certain experiments while exploring new avenues of investigation of defect control and reduction where appropriate. All work proposed was within the context of achieving an ODS Fe{sub 3}Al alloy of improved overall quality and potential creep performance (particularly) in the consolidated, release condition. The interim outturn of the experimental work performed is also reported.

  12. Coulomb screening in graphene with topological defects

    Science.gov (United States)

    Chakraborty, Baishali; Gupta, Kumar S.; Sen, Siddhartha

    2015-06-01

    We analyze the screening of an external Coulomb charge in gapless graphene cone, which is taken as a prototype of a topological defect. In the subcritical regime, the induced charge is calculated using both the Green's function and the Friedel sum rule. The dependence of the polarization charge on the Coulomb strength obtained from the Green's function clearly shows the effect of the conical defect and indicates that the critical charge itself depends on the sample topology. Similar analysis using the Friedel sum rule indicates that the two results agree for low values of the Coulomb charge but differ for the higher strengths, especially in the presence of the conical defect. For a given subcritical charge, the transport cross-section has a higher value in the presence of the conical defect. In the supercritical regime we show that the coefficient of the power law tail of polarization charge density can be expressed as a summation of functions which vary log periodically with the distance from the Coulomb impurity. The period of variation depends on the conical defect. In the presence of the conical defect, the Fano resonances begin to appear in the transport cross-section for a lower value of the Coulomb charge. For both sub and supercritical regime we derive the dependence of LDOS on the conical defect. The effects of generalized boundary condition on the physical observables are also discussed.

  13. Defects and metrology of ultrathin resist films

    Science.gov (United States)

    Okoroanyanwu, Uzodinma; Cobb, Jonathan L.; Dentinger, Paul M.; Henderson, Craig C.; Rao, Veena; Monahan, Kevin M.; Luo, David; Pike, Christopher

    2000-06-01

    Defectivity in spin-coated, but unpatterned ultrathin resist (UTR) films (EQ 1000 Angstrom) was studied in order to determine whether defectivity will present an issue in EUV (13.4-nm) and 157-nm lithographic technologies. These are the lithographic regimes where absorption issues mandate the use of ultrathin resists. Four resist samples formulated from the same Shipley UV6 polymer batch and having the same polymer molecular weight properties but different viscosities, were spin-coated at spin speeds ranging from 1000 to 5000 RPM on a production-grade track in a Class 1 pilot line facility. Defect inspection was carried out with KLA SP1/TBI tool, while defect review was carried out with JEOL 7515 SEM tool and KLA Ultrapointe Confocal Review Station (CRS) Microscope. The results obtained are related to the physical properties of the resist polymers, as well as to spin coating parameters. Also, the results of the defect inspection, review, characterization, and pareto are compared to those obtained on baseline thick resists (>= 3500 Angstrom) processed under similar condition as the ultra-thin resists. The results show that for a well-optimized coating process and within the thickness range explored (800 - 4200 Angstrom), there is no discernible dependence of defectivity on film thickness of the particular resists studied and on spin speed. Also assessed is the capability of the current metrology toolset for inspecting, reviewing, and classifying the various types of defects in UTR films.

  14. Point Defects in SiC

    Science.gov (United States)

    Zvanut, Mary Ellen

    2004-03-01

    Production of high frequency, high power electronic devices using wide bandgap semiconductors has spurred renewed interest in point defects in SiC. Recent electron paramagnetic resonance (EPR) spectroscopy studies focus on centers in as-grown high purity semi-insulating substrates because intrinsic defects are thought to compensate unavoidable shallow centers, thus creating the high resistivity required. The EPR studies address the chemical/structural composition of the defects, the defect level (energy with respect to a band edge with which the defect can accept or release an electron) and thermal stability. Thus far, the positively charged carbon vacancy, the Si vacancy, a carbon-vacancy/carbon antisite pair, and several as yet-unidentified centers have been observed in as-grown electronic-grade 4H-SiC [1-3]. The talk will review the types of defects recently identified in SiC and discuss their possible relationship to compensation. The photo-induced EPR experiments used to determine defect levels will be discussed, with a particular focus on the carbon vacancy. The use of high frequency EPR to resolve the many different types of centers in SiC will also be covered. Finally, the presentation will review the thermal stability of the intrinsic defects detected in as-grown 4H SiC. 1. M. E. Zvanut and V. V. Konovalov, Appl. Phys. Lett. 80, 410 (2002). 2. N.T. Son, Z. Zolnai, and E. Janzen, Phys. Rev. B64, 2452xx (2003). 3. W.E. Carlos, E.R. Glaser, and B.V. Shanabrook, in Proceedings of the 22nd conference on Defects in Semiconductors, Aarhus, Denmark, July 2003.

  15. The mechanics of defect detection in vibrothermography

    Science.gov (United States)

    Renshaw, Jeremy Blake

    Vibrothermography is a nondestructive evaluation (NDE) technique that is used to detect surface and sub-surface defects such as cracks, disbonds, and delaminations through observations of vibration-induced frictional heat generation at defects. Frictional heating is observed using an infrared (IR) camera and is used to determine the presence and location of defects. There is a large industrial interest in vibrothermography due to its ability to rapidly detect defects over a large area. Another motivation for using this technology is its ability to find defects, such as tightly-closed cracks, that can be missed using other common NDE techniques. A major hindrance to the widespread application of vibrothermography has been an inability to quantify the reliability and capability of the inspection due to insufficient knowledge of the underlying physics of vibrothermography. The purpose of this work is to further understand the physics controlling defect detection in vibrothermography. The influence of vibration was studied through the use of synthetic defects and noncontact measures of vibration. Numerous samples of aluminum, brass, titanium, and carbon fiber-reinforced polymer composites were used to study the physics of heat generation to isolate the different sources of heat generation in metals and composites. The effects of crack closure on heat generation were studied and a method was developed to accurately measure crack closure stresses using vibrothermography. Finally, the effect of friction and heat generation on rubbing crack faces was observed using techniques such as profilometry, optical microscopy, and scanning electron microscopy. This work describes some of the fundamental parameters affecting heat generation and methods to improve defect detection reliability. This research provides a foundation for creating statistical models to improve the defect detection process using vibrothermography.

  16. Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Carla Marques Rondon, E-mail: carlamcampos@uol.com.br [Universidade Federal de Mato Grosso, Cuiabá, MT (Brazil); Zanardo, Evelin Aline; Dutra, Roberta Lelis [Departamento de Patologia - Laboratório de Citogenômica - LIM 03 - Universidade de São Paulo, São Paulo, SP (Brazil); Kulikowski, Leslie Domenici [Universidade de São Paulo, São Paulo, SP (Brazil); Departamento de Patologia - Laboratório de Citogenômica - LIM 03 - Universidade de São Paulo, São Paulo, SP (Brazil); Kim, Chong Ae [Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-01-15

    Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations. Investigate gene copy number variation (CNV) in children with conotruncal heart defect. Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated. Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents. Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

  17. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.

    Science.gov (United States)

    Slavotinek, A M; Garcia, S T; Chandratillake, G; Bardakjian, T; Ullah, E; Wu, D; Umeda, K; Lao, R; Tang, P L-F; Wan, E; Madireddy, L; Lyalina, S; Mendelsohn, B A; Dugan, S; Tirch, J; Tischler, R; Harris, J; Clark, M J; Chervitz, S; Patwardhan, A; West, J M; Ursell, P; de Alba Campomanes, A; Schneider, A; Kwok, P-Y; Baranzini, S; Chen, R O

    2015-11-01

    Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.

  18. Defects of organization in rendering medical aid

    Directory of Open Access Journals (Sweden)

    Shavkat Islamov

    2010-09-01

    Full Text Available The defects of organization at the medical institution mean disturbance of rules, norms and order of rendering of medical aid. The number of organization defects in Uzbekistan increased from 20.42%, in 1999 to 25.46% in 2001 with gradual decrease to 19.9% in 2003 and 16.66%, in 2006 and gradual increase to 21.95% and 28.28% (P<0.05 in 2005 and 2008. Among the groups of essential defects of organization there were following: disturbance of transportation rules, lack of dispensary care, shortcomings in keeping medical documentation.

  19. Interdisciplinary Management of an Isolated Intrabony Defect

    Directory of Open Access Journals (Sweden)

    Sheetal Ghivari

    2014-01-01

    Full Text Available The treatment of intrabony defects is a real challenge in molar teeth as it is chronic, slowly progressing disease which needs timely intervention. Periodontal inflammation associated with intrabony defect is not a separate entity as it secondarily affects the pulp causing retrograde pulpitis. However, treatment of these lesions will be complicated due to extensive bone loss. The tooth was endodontically treated followed by periodontal surgery to eliminate the deep periodontal pocket and promote bone fill in osseous defect. PepGen P-15 composited with platelet rich plasma was utilized for enhancing bone formation. The combination of these graft materials provides synergistic effect on bone regeneration.

  20. Complement defects in patients with chronic rhinosinusitis

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Lange, Bibi; Kjeldsen, Anette D;

    2012-01-01

    whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper...... was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Our studies show that defects in the complement system collectively...

  1. Transgenic isolation of skeletal muscle and kidney defects in laminin beta2 mutant mice: Implications for Pierson syndrome

    OpenAIRE

    Miner, Jeffrey H.; Go, Gloriosa; Cunningham, Jeanette; Patton, Bruce L.; Jarad, George

    2006-01-01

    Pierson syndrome is a recently defined disease usually lethal within the first postnatal months and caused by mutations in the gene encoding laminin β2 (LAMB2). The hallmarks of Pierson syndrome are congenital nephrotic syndrome accompanied by ocular abnormalities, including microcoria (small pupils), with muscular and neurological developmental defects also present. Lamb2−/− mice are a model for Pierson syndrome; they exhibit defects in the kidney glomerular barrier, in the development and o...

  2. CDC Reports Six Cases of Birth Defects Caused by Zika

    Science.gov (United States)

    ... Reports Six Cases of Birth Defects Caused by Zika Three babies born with defects, while three pregnancies ... 2016 (HealthDay News) -- In the first reporting of Zika-related birth defects in the United States, federal ...

  3. 叶酸代谢关键酶基因多态性与儿童神经管缺陷的相关性%Association between single nucleotide polymorphisms of folate metabolism pathway genes and neural tube defects in children

    Institute of Scientific and Technical Information of China (English)

    石鸥燕; 吴波; 张瑞苹; 张鹏; 王春祥; 沈永明; 马骁; 张庆江; 蔡春泉

    2016-01-01

    Objective To analyze the association between single nucleotide polymorphisms (SNPs) of folate metabolism pathway genes and neural tube defects(NTDs) in children of Han population in northern China.Methods One hundred and fifty-two NTDs patients and 169 controls in a case-control study were examined.Sixteen SNPs in 5 genes were genotyped by Sequenom MassARRAY.Prediction of effects of mutations on protein function was performed with SIFT and PolyPhen programs.Results The distribution of allele and genotype frequencies of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) rs2236225 loci was significantly different between NTDs group and the healthy control group (x2 =5.292,6.080;P =0.021,0.048),and the children with A allele and AA genotype were associated with increased NTDs risk compared with G allele and GG genotype (OR =1.500,95% CI 1.061-2.120;OR =2.862,95% CI 1.022-8.015).The distribution of allele and genotype frequencies of methylenetetrahydrofolate reductase (MTHFR) rs1801133 loci was significantly different between NTDs group and the healthy control group(x2 =7.403,6.973;P =0.007,0.031),and the children with T allele and TF genotype were associated with increased NTDs risk compared with C allele and CC genotype(OR =1.552,95% CI 1.130-2.131;OR =2.344,95% CI 1.233-4.457).The distribution of allele and genotype frequencies of methionine synthase reductase(MTRR) rs1801394 loci was significantly different between NTDs group and the healthy control group(x2 =6.365,6.219;P =0.012,0.045),and the children with G allele and GG genotype were associated with increased NTDs risk compared with A allele and AA genotype (OR =1.553,95 % CI 1.102 ~ 2.188;OR =2.355,95 % CI 1.044-5.312).There was no difference in other loci among different genotypes or alleles.SIFT and Polyphen programs showed that the prediction results were damaging and probably damaging (MTHFR rs1801133 and MTRR rs1801394).Conclusions The rs2236225 of MTHFD1 gene,rs1801133 of MTHFR gene and rs

  4. Sex ratios among infants with birth defects, National Birth Defects Prevention Study, 1997-2009.

    Science.gov (United States)

    Michalski, Adrian M; Richardson, Sandra D; Browne, Marilyn L; Carmichael, Suzan L; Canfield, Mark A; VanZutphen, Alissa R; Anderka, Marlene T; Marshall, Elizabeth G; Druschel, Charlotte M

    2015-05-01

    A small number of population-based studies have examined sex differences among infants with birth defects. This study presents estimates of sex ratio for both isolated cases and those with multiple congenital anomalies, as well as by race/ethnicity. Male-female sex ratios and their 95% confidence intervals were calculated for 25,952 clinically reviewed case infants included in the National Birth Defects Prevention Study (1997-2009), a large population-based case-control study of birth defects. The highest elevations in sex ratios (i.e., male preponderance) among isolated non-cardiac defects were for craniosynostosis (2.12), cleft lip with cleft palate (2.01), and cleft lip without cleft palate (1.78); the lowest sex ratios (female preponderance) were for choanal atresia (0.45), cloacal exstrophy (0.46), and holoprosencephaly (0.64). Among isolated cardiac defects, the highest sex ratios were for aortic stenosis (2.88), coarctation of the aorta (2.51), and d-transposition of the great arteries (2.34); the lowest were multiple ventricular septal defects (0.52), truncus arteriosus (0.63), and heterotaxia with congenital heart defect (0.64). Differences were observed by race/ethnicity for some but not for most types of birth defects. The sex differences we observed for specific defects, between those with isolated versus multiple defects, as well as by race/ethnicity, demonstrate patterns that may suggest etiology and improve classification. PMID:25711982

  5. Molecular signatures of cardiac defects in Down syndrome lymphoblastoid cell lines suggest altered ciliome and Hedgehog pathways.

    Directory of Open Access Journals (Sweden)

    Clémentine Ripoll

    Full Text Available Forty percent of people with Down syndrome exhibit heart defects, most often an atrioventricular septal defect (AVSD and less frequently a ventricular septal defect (VSD or atrial septal defect (ASD. Lymphoblastoid cell lines (LCLs were established from lymphocytes of individuals with trisomy 21, the chromosomal abnormality causing Down syndrome. Gene expression profiles generated from DNA microarrays of LCLs from individuals without heart defects (CHD(-; n = 22 were compared with those of LCLs from patients with cardiac malformations (CHD(+; n = 21. After quantile normalization, principal component analysis revealed that AVSD carriers could be distinguished from a combined group of ASD or VSD (ASD+VSD carriers. From 9,758 expressed genes, we identified 889 and 1,016 genes differentially expressed between CHD(- and AVSD and CHD(- and ASD+VSD, respectively, with only 119 genes in common. A specific chromosomal enrichment was found in each group of affected genes. Among the differentially expressed genes, more than 65% are expressed in human or mouse fetal heart tissues (GEO dataset. Additional LCLs from new groups of AVSD and ASD+VSD patients were analyzed by quantitative PCR; observed expression ratios were similar to microarray results. Analysis of GO categories revealed enrichment of genes from pathways regulating clathrin-mediated endocytosis in patients with AVSD and of genes involved in semaphorin-plexin-driven cardiogenesis and the formation of cytoplasmic microtubules in patients with ASD-VSD. A pathway-oriented search revealed enrichment in the ciliome for both groups and a specific enrichment in Hedgehog and Jak-stat pathways among ASD+VSD patients. These genes or related pathways are therefore potentially involved in normal cardiogenesis as well as in cardiac malformations observed in individuals with trisomy 21.

  6. Evidence for the "midline" hypothesis in associated defects of laterality formation and multiple midline anomalies.

    Science.gov (United States)

    Gilbert-Barness, E; Debich-Spicer, D; Cohen, M M; Opitz, J M

    2001-07-15

    A male infant was liveborn at 38 weeks of gestation to a G4P1AB2, 22-year-old, mother. Polyhydramnios and multiple congenital anomalies were noted by ultrasonography; the infant died 5 min after birth. At autopsy, the infant had multiple defects of blastogenesis including midline anomalies with asplenia and abnormalities of laterality formation. The laterality defects were unusual in that they combined asplenia with hypoplastic, symmetrically unilobate lungs and bilateral hyparterial bronchi more consistent with polysplenia, abdominal situs inversus with midline stomach, symmetric liver, and left gallbladder. No intracardiac abnormalities were present, but there was azygous continuation of the inferior vena cava. Additional multiple midline defects included bronchoesophageal fistula, duodenal atresia, absence of posterior leaf of diaphragm; horseshoe adrenal gland; microcephaly; Dandy-Walker anomaly with agenesis of cerebellar vermis and occipital encephalocele; holoprosencephaly with orbital encephalocele, midline defect of the orbital plate of the skull, bilateral anophthalmia, double proboscis with bilateral choanal atresia, midline upper lip and palatal cleft; single-lobed thyroid; hypoplastic external genitalia with midline cleft of scrotum, long tapering fingers, and defects of the cranium at the sites of orbital and occipital encephaloceles. Defects of laterality frequently are associated with other complex midline anomalies, which both result from a disturbance of pattern formation during blastogenesis, i.e., the induction of the progenitor fields. The latter are the result of the establishment of upstream expression domains of growth and transcription factors and other morphogens. Many of these and other genetic systems, expressed asymmetrically around the midline, are responsible for laterality formation and are the result of upstream and subsequent downstream gene expression cascades through the expression of genes such as HOX genes; bFGF; transforming

  7. ILT based defect simulation of inspection images accurately predicts mask defect printability on wafer

    Science.gov (United States)

    Deep, Prakash; Paninjath, Sankaranarayanan; Pereira, Mark; Buck, Peter

    2016-05-01

    At advanced technology nodes mask complexity has been increased because of large-scale use of resolution enhancement technologies (RET) which includes Optical Proximity Correction (OPC), Inverse Lithography Technology (ILT) and Source Mask Optimization (SMO). The number of defects detected during inspection of such mask increased drastically and differentiation of critical and non-critical defects are more challenging, complex and time consuming. Because of significant defectivity of EUVL masks and non-availability of actinic inspection, it is important and also challenging to predict the criticality of defects for printability on wafer. This is one of the significant barriers for the adoption of EUVL for semiconductor manufacturing. Techniques to decide criticality of defects from images captured using non actinic inspection images is desired till actinic inspection is not available. High resolution inspection of photomask images detects many defects which are used for process and mask qualification. Repairing all defects is not practical and probably not required, however it's imperative to know which defects are severe enough to impact wafer before repair. Additionally, wafer printability check is always desired after repairing a defect. AIMSTM review is the industry standard for this, however doing AIMSTM review for all defects is expensive and very time consuming. Fast, accurate and an economical mechanism is desired which can predict defect printability on wafer accurately and quickly from images captured using high resolution inspection machine. Predicting defect printability from such images is challenging due to the fact that the high resolution images do not correlate with actual mask contours. The challenge is increased due to use of different optical condition during inspection other than actual scanner condition, and defects found in such images do not have correlation with actual impact on wafer. Our automated defect simulation tool predicts

  8. Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisong [ORNL; Liu, Yie [ORNL

    2006-01-01

    Msh2 is a key mammalian DNA mismatch repair (MMR) gene and mutations or deficiencies in mammalian Msh2 gene result in microsatellite instability (MSI+) and the development of cancer. Here, we report that primary mouse embryonic fibroblasts (MEFs) deficient in the murine MMR gene Msh2 (Msh2-/-) showed a significant increase in chromosome aneuploidy, centrosome amplification, and defective mitotic spindle organization and unequal chromosome segregation. Although Msh2-/- mouse tissues or primary MEFs had no apparent change in telomerase activity, telomere length, or recombination at telomeres, Msh2-/- MEFs showed an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA. These data suggest that MSH2 helps to maintain genomic stability through the regulation of the centrosome and normal telomere capping in vivo and that defects in MMR can contribute to oncogenesis through multiple pathways.

  9. Holographic entanglement entropy of surface defects

    Science.gov (United States)

    Gentle, Simon A.; Gutperle, Michael; Marasinou, Chrysostomos

    2016-04-01

    We calculate the holographic entanglement entropy in type IIB supergravity solutions that are dual to half-BPS disorder-type surface defects in N=4 supersymmetric Yang-Mills theory. The entanglement entropy is calculated for a ball-shaped region bisected by a surface defect. Using the bubbling supergravity solutions we also compute the expectation value of the defect operator. Combining our result with the previously-calculated one-point function of the stress tensor in the presence of the defect, we adapt the calculation of Lewkowycz and Maldacena [1] to obtain a second expression for the entanglement entropy. Our two expressions agree up to an additional term, whose possible origin and significance is discussed.

  10. [Defect replacement with osteogenin containing gelatin].

    Science.gov (United States)

    Thielemann, F W; Feller, A M; Schmidt, K

    1984-01-01

    In order to demonstrate an alternative way to correct diaphyseal defects allogenic cortical bone prepared as "osteogenin containing gelatine (OCG)" was used in sheep. Animals without any implants served as controls. Healing was assessed by radiological examination after 3, 6, 9 and 12 weeks and histological examination after 12 weeks. In the control group there was no bridging of the defect in all of the four animals. Out of the six animals of the OCG-group one animal suffered from a postoperative infection and one animal failed because of a breakdown of the osteosynthesis. The other four animals exhibited a complete reconstruction of the former defect roentgenologically after 9 weeks. Histologically a new formed spongious bone could be demonstrated in the former defective site. The OCG-implants were completely resorbed after 12 weeks. PMID:6395536

  11. Simulating point defects in cubic monocarbides

    International Nuclear Information System (INIS)

    Calculations have been performed on point-defect formation and migration parameters for cubic monocarbides on the basis of simple models: rigid pair bonds and an elastic continuum. However, they do not indicate how relaxation affects defect characteristics. Here the authors examine lattice relaxation around point defects by computer simulation. Atomic interaction potentials have been considered for cubic monocarbides. The volume dependence of the potential energy has been examined for ideal crystals of TiC, ZrC, HfC, VC, NbC, TaC, ThC, UC, PuC. Energy and structural characteristics have been derived for the relaxation of the lattice around vacancies and defects of substitutional type

  12. Apparatus for locating defective nuclear fuel elements

    International Nuclear Information System (INIS)

    An ultrasonic search unit for locating defective fuel elements within a fuel assembly used in a water cooled nuclear reactor is presented. The unit is capable of freely traversing the restricted spaces between the fuel elements

  13. Electronic structure of point defects in semiconductors

    International Nuclear Information System (INIS)

    This 'Habilitation a diriger des Recherches' memoir presents most of my scientific activities during the past 7 years, in the field of electronic structure calculations of defects in solids. Point defects (vacancies, interstitials, impurities) in functional materials are a key parameter to determine if these materials will actually fill the role they have been assigned or not. Indeed, the presence of defects cannot be avoided when the temperature is increased or when the material is subjected to external stresses, such as irradiation in the nuclear reactors and in artificial satellites with solar radiations. However, in many cases, defects are introduced in the materials on purpose to tune the electronic transport, optical or even magnetic properties. This procedure is called the doping of semiconductors, which is the foundation technique for transistors, diodes, or photovoltaic cells. However, doping is not always straightforward and unexpected features may occur, such as doping asymmetry or Fermi level pinning, which can only be explained by complex phenomena involving different types of defects or complexes of defects. In this context, the calculations of electronic structure ab initio is an ideal tool to complement the experimental observations, to gain the understanding of phenomena at the atomic level, and even to predict the properties of defects. The power of the ab initio calculations comes from their ability to describe any system of electrons and nuclei without any specific adjustment. But although there is a strong need for numerical simulations in this field, the ab initio calculations for defects are still under development as of today. The work presented in this memoir summarizes my contributions to methodological developments on this subject. These developments have followed two main tracks. The first topic is the better understanding of the unavoidable finite size effects. Indeed, defects in semiconductors or insulators are generally present in

  14. Color Vision Defects: What Teachers Should Know.

    Science.gov (United States)

    Lewis, Barbara A.; And Others

    1990-01-01

    Discusses the nature of color vision defects as they relate to reading instruction. Suggests ways that teachers can adapt instruction to help provide maximal learning opportunities for the color deficient child. (RS)

  15. Topological defect dynamics in operando battery nanoparticles

    Science.gov (United States)

    Ulvestad, A.; Singer, A.; Clark, J. N.; Cho, H. M.; Kim, J. W.; Harder, R.; Maser, J.; Meng, Y. S.; Shpyrko, O. G.

    2015-06-01

    Topological defects can markedly alter nanomaterial properties. This presents opportunities for “defect engineering,” where desired functionalities are generated through defect manipulation. However, imaging defects in working devices with nanoscale resolution remains elusive. We report three-dimensional imaging of dislocation dynamics in individual battery cathode nanoparticles under operando conditions using Bragg coherent diffractive imaging. Dislocations are static at room temperature and mobile during charge transport. During the structural phase transformation, the lithium-rich phase nucleates near the dislocation and spreads inhomogeneously. The dislocation field is a local probe of elastic properties, and we find that a region of the material exhibits a negative Poisson’s ratio at high voltage. Operando dislocation imaging thus opens a powerful avenue for facilitating improvement and rational design of nanostructured materials.

  16. Infrared Computations of Defect Schur Indices

    CERN Document Server

    Cordova, Clay; Shao, Shu-Heng

    2016-01-01

    We conjecture a formula for the Schur index of N=2 four-dimensional theories in the presence of boundary conditions and/or line defects, in terms of the low-energy effective Seiberg-Witten description of the system together with massive BPS excitations. We test our proposal in a variety of examples for SU(2) gauge theories, either conformal or asymptotically free. We use the conjecture to compute these defect-enriched Schur indices for theories which lack a Lagrangian description, such as Argyres-Douglas theories. We demonstrate in various examples that line defect indices can be expressed as sums of characters of the associated two-dimensional chiral algebra and that for Argyres-Douglas theories the line defect OPE reduces in the index to the Verlinde algebra.

  17. International conference on defects in insulating crystals

    International Nuclear Information System (INIS)

    Short summaries of conference papers are presented. Some of the conference topics included transport properties, defect levels, superionic conductors, radiation effects, John-Teller effect, electron-lattice interactions, and relaxed excited states

  18. Thermodynamics of Cosmic Defect Network Evolution

    CERN Document Server

    Avelino, P P

    2015-01-01

    We show that simple thermodynamic conditions determine, to a great extent, the equation of state and dynamics of cosmic defects of arbitrary dimensionality. We use these conditions to provide a more direct derivation of the Velocity-dependent One-Scale (VOS) model for the macroscopic dynamics of topological defects of arbitrary dimensionality in a $N+1$-dimensional homogeneous and isotropic universe. We parameterize the modifications to the VOS model associated to the interaction of the topological defects with other fields, including, in particular, a new dynamical degree of freedom associated to the variation of the mass per unit $p$-area of the defects, and compute the corresponding scaling solutions. The observational impact of this new dynamical degree of freedom is also briefly discussed.

  19. Color defects in a gauge condensate

    CERN Document Server

    Dzhunushaliev, V

    2006-01-01

    The model of an approximate non-perturbative calculations in the SU(3) gauge theory is offered. This approach is based on the separation of initial degrees of freedom on ordered and disordered phases. The ordered phase is almost classical degrees of freedom, the disordered phase is completely quantum degrees of freedom. Using some approximations and simplifications for 2 and 4-points Green's functions an effective Lagrangian describing both phases from the SU(3) Lagrangian is obtained. The calculations show that ordered phase is squeezed by disordered phase into defects. These defects are: an infinite flux tube filled with longitudinal color electric and magnetic fields; a color electric hedgehog; a defect having either two color electric dipoles + two color magnetic dipoles or two color electric dipoles or two color magnetic dipoles. It assumed that the color defects are quantum excitations in a gauge condensate.

  20. Congenital Heart Defects and Physical Activity

    Science.gov (United States)

    ... Tools & Resources Stroke More Congenital Heart Defects and Physical Activity Updated:Apr 19,2016 Exercise Is for Everyone ... almost all patients do some form of regular physical activity. There are a few exceptions, so it's good ...

  1. Fabric Defect Detection Using Adaptive Wavelet Transform

    Institute of Scientific and Technical Information of China (English)

    LI Li-qing; HUANG Xiu-bao

    2002-01-01

    A method of woven fabric defect detection using the wavelet transform adaptive to the fabric has been developed. With reference to the orthogonality constrains of Daubechies wavelet, by taking the mmimization of the energy or the gray level of the pixels in the output sub-images as the additional conditions and using the random algorithm method, two sets of wavelet filters adapted to the fabric texture were formed. The original images of normal fabric texture and the fabric texture with defects were decomposed into horizontal and vertical sub- images by using these filters and the feature indices of these sub-images were also extracted. By comparing the feature indices of the normal texture with that of the defective texture, the fabric defects can be successfully detected and located.

  2. Holographic entanglement entropy of surface defects

    CERN Document Server

    Gentle, Simon A; Marasinou, Chrysostomos

    2015-01-01

    We calculate the holographic entanglement entropy in type IIB supergravity solutions that are dual to half-BPS disorder-type surface defects in ${\\cal N}=4$ Super Yang-Mills theory. The entanglement entropy is calculated for a ball-shaped region bisected by a surface defect. Using the bubbling supergravity solutions we also compute the expectation value of the defect operator. Combining our result with the previously-calculated one-point function of the stress tensor in the presence of the defect, we adapt the calculation of Lewkowycz and Maldacena to obtain a second expression for the entanglement entropy. Our two expressions agree up to an additional term, whose possible origin and significance is discussed

  3. Di-interstitial defect in silicon revisited

    Energy Technology Data Exchange (ETDEWEB)

    Londos, C. A.; Antonaras, G. [Solid State Section, Physics Department, University of Athens, Panepistimiopolis, Zografos, 157 84 Athens (Greece); Chroneos, A. [Engineering and Innovation, The Open University, Milton Keynes MK7 6AA (United Kingdom); Department of Materials, Imperial College London, London SW7 2BP (United Kingdom)

    2013-11-21

    Infrared spectroscopy was used to study the defect spectrum of Cz-Si samples following fast neutron irradiation. We mainly focus on the band at 533 cm{sup −1}, which disappears from the spectra at ∼170 °C, exhibiting similar thermal stability with the Si-P6 electron paramagnetic resonance (EPR) spectrum previously correlated with the di-interstitial defect. The suggested structural model of this defect comprises of two self-interstitial atoms located symmetrically around a lattice site Si atom. The band anneals out following a first-order kinetics with an activation energy of 0.88 ± 0.3 eV. This value does not deviate considerably from previously quoted experimental and theoretical values for the di-interstitial defect. The present results indicate that the 533 cm{sup −1} IR band originates from the same structure as that of the Si-P6 EPR spectrum.

  4. Focal skin defect, limb anomalies and microphthalmia.

    NARCIS (Netherlands)

    Jackson, K.E.; Andersson, H.C.

    2004-01-01

    We describe two unrelated female patients with congenital single focal skin defects, unilateral microphthalmia and limb anomalies. Growth and psychomotor development were normal and no brain malformation was detected. Although eye and limb anomalies are commonly associated, clinical anophthalmia and

  5. Point defects dynamics in a stress field

    International Nuclear Information System (INIS)

    The dependence of anisotropic defect diffusion on stress is studied for a hexagonal close packed (hcp) material under irradiation and uniaxially stressed. The diffusion is described as a discrete process of thermally activated jumps. It is shown that the presence of an external stress field enhances the intrinsic anisotropic diffusion, being this variation determined by the defect dipole tensors' symmetry in the equilibrium and saddle point configurations. Also, the point defect diffusion equations to sinks, like edge dislocations and spherical cavities, are solved and the sink strengths are calculated. The conclusion is that the dynamics of the interaction between defects and sinks is controlled by the changes in diffusivity induced by stress fields. (Author)

  6. Model Tests of Pile Defect Detection

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The pile, as an important foundation style, is being used in engineering practice. Defects of different types and damages of different degrees easily occur during the process of pile construction. So,dietecting defects of the pile is very important. As so far, there are some difficult problems in pile defect detection. Based on stress wave theory, some of these typical difficult problems were studied through model tests. The analyses of the test results are carried out and some significant results of the low-strain method are obtained, when a pile has a gradually-decreasing crosssection part, the amplitude of the reflective signal originating from the defect is dependent on the decreasing value of the rate of crosssection β. No apparent signal reflected from the necking appeares on the velocity response curve when the value of β is less than about 3.5 %.

  7. Genetic Counseling for Congenital Heart Defects

    Science.gov (United States)

    ... High Blood Pressure Tools & Resources Stroke More Genetic Counseling for Congenital Heart Defects Updated:Oct 26,2015 ... with congenital heart disease considers having children. Genetic counseling can help answer these questions and address your ...

  8. International conference on defects in insulating crystals

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    Short summaries of conference papers are presented. Some of the conference topics included transport properties, defect levels, superionic conductors, radiation effects, John-Teller effect, electron-lattice interactions, and relaxed excited states. (SDF)

  9. Magnetism induced by single-atom defects in nanographites.

    OpenAIRE

    Yazyev, Oleg V.; Helm, Lothar

    2007-01-01

    We study from first principles the magnetism in graphene induced by single carbon atom defects. For two types of defects considered in our study, the hydrogen chemisorption defect and the vacancy defect, the magnetism due to the defect-induced extended states has been observed. Calculated magnetic moments are equal to 1 μB per hydrogen chemisorption defect and ∼1.5 μB per vacancy defect. The magnetic ordering is either ferromagnetic or antiferromagnetic, depending on whether the defects corre...

  10. Reconstructing the extended nasal tip defect.

    Science.gov (United States)

    Mobley, Steven

    2013-10-01

    Reconstruction of large facial defects requires surgical skill, an understanding of engineering principles, an artistic eye, and patience to design the most elegant solution for each patient. Extended nasal tip defects, which may involve additional facial subunits, require even more thoughtful analysis and planning. Reconstructive surgeons need to be aware of the pros and cons of various options for flaps, the use of a delay stage, and sequencing and scheduling of staged operations to achieve an optimal outcome. PMID:24037937

  11. Radioactive fallout and neural tube defects

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2015-10-01

    Full Text Available Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate since the Chernobyl nuclear fallout in 1986. A recent report on the incidence of neural defects in the west coast of USA, following Fukushima disaster, brought another evidence for effect of radioactive fallout on the occurrence of NTD’s. Here a literature review was performed focusing on this special subject.

  12. Topological Defects in Liquid Crystal Films

    Institute of Scientific and Technical Information of China (English)

    DUAN Yi-Shi; ZHAO Li; ZHANG Xin-Hui; SI Tie-Yan

    2007-01-01

    A topological theory of liquid crystal films in the presence of defects is developed based on the φ-mapping topological current theory. By generalizing the free-energy density in "one-constant" approximation, a covariant freeenergy density is obtained, from which the U(1) gauge field and the unified topological current for monopoles and strings in liquid crystals are derived. The inner topological structure of these topological defects is characterized by the winding numbers of φ-mapping.

  13. Requirement Defect Identification: An Early Stage Perspective

    OpenAIRE

    Md. Rizwan Beg; Sandeep Kumar Nayak; Khan, Raees A.

    2012-01-01

    Delivery of reliable software has become a primary concern for the successful software development organizations. Successful and reliable software can be delivering only when the requirement documentation is reliable. There is various threats point in the requirement phase that causes for requirement defects and so defect occurring in the further phases of Software Development process. A key aspect of delivering and improving the software reliability it is necessary to be confident that the r...

  14. Defects of organization in rendering medical aid

    OpenAIRE

    Shavkat Islamov

    2010-01-01

    The defects of organization at the medical institution mean disturbance of rules, norms and order of rendering of medical aid. The number of organization defects in Uzbekistan increased from 20.42%, in 1999 to 25.46% in 2001 with gradual decrease to 19.9% in 2003 and 16.66%, in 2006 and gradual increase to 21.95% and 28.28% (P

  15. Defects and multistability in eutectic solidification patterns

    OpenAIRE

    Parisi, Andrea; Plapp, Mathis

    2010-01-01

    We use three-dimensional phase-field simulations to investigate the dynamics of the two-phase composite patterns formed upon during solidification of eutectic alloys. Besides the spatially periodic lamellar and rod patterns that have been widely studied, we find that there is a large number of additional steady-state patterns which exhibit stable defects. The defect density can be so high that the pattern is completely disordered, and that the distinction between lamellar and rod patterns is ...

  16. Terminal osseous dysplasia with pigmentary defects (TODPD) due to a recurrent filamin A (FLNA) mutation.

    Science.gov (United States)

    Brunetti-Pierri, Nicola; Torrado, Maria; Fernandez, Maria Del Carmen; Tello, Ana Maria; Arberas, Claudia L; Cardinale, Antonella; Piccolo, Pasquale; Bacino, Carlos A

    2014-11-01

    Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies, pigmentary skin defects, digital fibromas, and generalized bone involvement due to a recurrent mutation in the filamin A (FLNA) gene. We here report the mutation c.5217G>A in FLNA in three families with TODPD and we found possible germline and somatic mosaicism in two out of the three families. The occurrence of somatic and germline mosaicism for TODPD indicates that caution should be taken in counseling recurrence risks for these conditions upon presentation of an isolated case.

  17. Gene therapy for lung inflammatory diseases: not so far away?

    OpenAIRE

    Sallenave, J M; Porteous, D. J.; Haslett, C

    1997-01-01

    The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for...

  18. Topological Defects in Liquid Crystals: Studying the Correlation between Defects and Curvature

    Science.gov (United States)

    Melton, Charles

    2015-03-01

    Topological defects have recently been the subject of many fascinating studies in soft condensed matter physics. In particular, linking the evolution of topological defects to curvature changes has been a focus, leading possible applications in the areas such as cosmetics, pharmaceuticals, and electronics. In this study, defects in nematic liquid crystal droplets are investigated via laboratory and theoretical techniques. Nematic liquid crystal defects are reproduced via Monte Carlo simulations using a modified 2D XY-Model Hamiltonian. The simulation is performed on a curved surface to replicate a nematic droplet and examine possible defect configurations. To complement this theoretical work, we have trapped nematic droplets inside a dual-beam optical trap. This system allows controllable non-contact droplet deformation on a microscope based platform. Future work will focus on using the trap to stretch nematic droplets, correlating the changing topological defects with theoretical predictions.

  19. EUV actinic defect inspection and defect printability at the sub-32 nm half pitch

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Sungmin; Kearney, Patrick; Wurm, Stefan; Goodwin, Frank; Han, Hakseung; Goldberg, Kenneth; Mochi, Iacopp; Gullikson, Eric M.

    2009-08-01

    Extreme ultraviolet (EUV) mask blanks with embedded phase defects were inspected with a reticle actinic inspection tool (AIT) and the Lasertec M7360. The Lasertec M7360, operated at SEMA TECH's Mask Blank Development Center (MBDC) in Albany, NY, has a sensitivity to multilayer defects down to 40-45 nm, which is not likely sufficient for mask blank development below the 32 nm half-pitch node. Phase defect printability was simulated to calculate the required defect sensitivity for a next generation blank inspection tool to support reticle development for the sub-32 nm half-pitch technology node. Defect mitigation technology is proposed to take advantage of mask blanks with some defects. This technology will reduce the cost of ownership of EUV mask blanks. This paper will also discuss the kind of infrastructure that will be required for the development and mass production stages.

  20. Highly birefringent extruded elliptical-hole photonic crystal fibers with single defect and double defects

    Institute of Scientific and Technical Information of China (English)

    Zhongjiao He

    2009-01-01

    Highly birefringent elliptical-hole photonic crystal fibers(PCFs)with single defect and double defects are proposed,which are suppoosed to be achieved by extruding normal circular-hole PCFs based on a triangular lattice photonic crystal structure.Comparative research on the birefringence and the confinement loss of the proposed PCFs with single defect and double defects is presented.Simulation results show that the proposed PCFs with single defect and double defects can be with high birefringence(even up to the order of 10-2).The confinement loss increases when the ellipticity of the air hole of the PCFs increases,which nevertheless can be overconle by increasing the ring number or the area of the air holes in the fiber cladding.

  1. 表达猪圆环病毒2型Cap蛋白重组复制缺陷型人5型腺病毒的构建及小鼠免疫试验%Construction and Immunogenicity Analysis of Recombinant Replication-defective Human Adenovirus Type 5 Bearing the Porcine Circovirus Type 2 Cap Protein Gene

    Institute of Scientific and Technical Information of China (English)

    宫婷; 张守峰; 刘晔; 孙程龙; 杨洋; 陈奇; 钱方; 刘博浩; 扈荣良

    2013-01-01

    To construct a recombinant replication-defective human adenovirus type 5 expressing Cap protein of PCV2 and test the immunological efficacy in mice. In this study, the recombinant replication-defective human adenovirus type 5, named as rAd5-Cap (wt-rAd5), was constructed through homologous recombination internally in the HEK293AD cells after co-transfection of the Pac I-linearized backbone plasmid and the shuttle plasmid pacAd5CMV-Cap containing the open reading frame (ORF2) of the porcine circovirus type 2 (PCV2) cap protein or pacAd5CMV without inserted fragment. Furthermore, the rAd5-Cap could induce the expression of PCV2 cap protein in the HEK293AD cells with high efficacy evaluated by the RT-PCR and indirect immunofluorescence assay (IFA). The virus titer of rAd5-Cap could reach up. To 108'5 TCID50/mL similarly to that of wt-rAd5, indicating that there was little affect on the virus proliferation after the insertion of PCV2 cap protein gene. The humeral immune responses could be activated and detected 14 days after the inoculation of the mice with 107 TCID50 rAd5-Cap intramuscularly, and constantly in crease in another 14 days. These molecular biological and animal experiments results demonstrated that the PCV2 cap protein could be efficiently expressed by the recombinant adenovirus rAd5-Cap in eukaryotic cells and induce robust immune responses in mice, which laid a good foundation for the development of new type vaccine against porcine circovirus.%构建表达猪圆环病毒2型Cap蛋白重组复制缺陷型人5型腺病毒,评价其对小鼠免疫效果.本研究将编码PCV2-Cap蛋白的ORF2克隆到腺病毒表达系统穿梭质粒,构建了重组穿梭质粒pacAd5CMV-Cap.将被限制性内切酶PacⅠ线性化后的骨架质粒和重组穿梭质粒共转染HEK293AD细胞,两者在真核细胞内同源重组并包装出携带PCV2-Cap基因的复制缺陷型重组人5型腺病毒,命名为rAd5-Cap;以同样方法重组获得了不含任何靶基因的

  2. Protein defects in neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Vainzof M.

    2003-01-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3, from the extracellular matrix (alpha2-laminin, collagen VI, from the sarcomere (telethonin, myotilin, titin, nebulin, from the muscle cytosol (calpain 3, TRIM32, from the nucleus (emerin, lamin A/C, survival motor neuron protein, and from the glycosylation pathway (fukutin, fukutin-related protein have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

  3. Ultrasonic defects measurements of fuel welded joints

    International Nuclear Information System (INIS)

    Fuel elements welding joints of atomic power station should provide hermetic state of sheath in the course of exploitation period. The quality of welded joints is determined by non-destructive methods of control. Weld width and defects' evidence are determined by ultrasonic means in butt resistance welding joints of fuel elements. The boundary of a weld line is not structurally heterogeneous, so the reflection of waves with the frequency up to 50 MHz is not observed, that allows to obtain high sensitivity to small defects with opening of ∼ 0.4 x 10-3 mm. The best results could be achieved by means of supervision of two-dimensional images of defects. The program of data processing makes it possible to measure the width of the weld with the accuracy of ± 0.1 mm and sizes of defects. Fast generation (∼ 25 sec.) of weld images at C and B - scanning could be obtained as well. High sensitivity to small defects occurs through utilization of diffraction of spherical ultrasonic wave's effect. The proposed method of defects' measurements could be applied to different technical problems of atomic industry and mechanical engineering. (author)

  4. Computational defect review for actinic mask inspections

    Science.gov (United States)

    Morgan, Paul; Rost, Daniel; Price, Daniel; Corcoran, Noel; Satake, Masaki; Hu, Peter; Peng, Danping; Yonenaga, Dean; Tolani, Vikram

    2013-04-01

    As optical lithography continues to extend into low-k1 regime, resolution of mask patterns continues to diminish. The limitation of 1.35 NA posed by water-based lithography has led to the application of various resolution enhancement techniques (RET), for example, use of strong phase-shifting masks, aggressive OPC and sub-resolution assist features, customized illuminators, etc. The adoption of these RET techniques combined with the requirements to detect even smaller defects on masks due to increasing MEEF, poses considerable challenges for a mask inspection engineer. Inspecting masks under their actinic-aerial image conditions would detect defects that are more likely to print under those exposure conditions. However, this also makes reviewing such defects in their low-contrast aerial images very challenging. On the other hand, inspecting masks under higher resolution inspection optics would allow for better viewing of defects post-inspection. However, such inspections generally would also detect many more defects, including printable and nuisance, thereby making it difficult to judge which are of real concern for printability on wafer. Often, an inspection engineer may choose to use Aerial and/or high resolution inspection modes depending on where in the process flow the mask is and the specific device-layer characteristics of the mask. Hence, a comprehensive approach is needed in handling defects both post-aerial and post-high resolution inspections. This analysis system is designed for the Applied Materials Aera™ mask inspection platform, all data reported was collected using the Aera.

  5. Complement defects in patients with chronic rhinosinusitis.

    Directory of Open Access Journals (Sweden)

    Maria Q Gaunsbaek

    Full Text Available The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS, and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.

  6. Characterization of the relA Gene of Porphyromonas gingivalis

    OpenAIRE

    Sen, Keya; Hayashi, Jun-ichiro; Kuramitsu, Howard K.

    2000-01-01

    Based upon the nucleotide sequence of the relA gene from Escherichia coli, a gene fragment corresponding to the homologous gene from the pathogenic oral bacterium Porphyromonas gingivalis 381 was isolated by PCR and utilized to construct a relA mutant. The mutant, KS7, was defective in ribosome-mediated ppGpp formation and also in the stringent response.

  7. Prenatal diagnosis of fetal aortopulmonary septal defect with ventricular septal defect by two-dimension echocardiography

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Fetal aortopulmonary septal defect (APSD) is an extremely rare condition, accounting for 0.1%-0.2% of all cardiac defects in live births world wide.1 Hospital mortality is 13% and 33% for simple and complex APSD, respectively.2 This rare cardiac defect refers to a congenital malformation in the development of the arteriosus truncus septum, and is usually associated with a wide variety of other structural cardiac anomalies such as ventricular septal defect (VSD), pulmonary valve stegnosis and so on.3 Prenatal diagnosis of an APSD is possible by echocardiography.

  8. System for Analyzing Microscopic Defects and Defect Propagation Due to Aging Project

    Data.gov (United States)

    National Aeronautics and Space Administration — New technology is needed for sensing and characterizing incipient defects, and assessing the effects of aging in aerospace components. Next generation materials,...

  9. Automated defect review of the wafer bevel with a defect review scanning electron microscope

    Science.gov (United States)

    McGarvey, Steve; Kanezawa, Masakazu

    2009-03-01

    One of the few remaining bastions of non-regulated Integrated Circuit defectivity is the wafer bevel. Recent internal Integrated Circuit Manufacturing studies have suggested that the edge bevel may be responsible for as much as a two to three percent yield loss during a defect excursion on the manufacturing line and a one to two percent yield loss during ongoing wafer manufacturing. A new generation of defect inspection equipment has been introduced to the Research and Development, Integrated Circuit, MEM's and Si wafer manufacturing markets that has imparted the ability for the end equipment user to detect defects located on the bevel of the wafer. The inherent weakness of the current batch of wafer bevel inspection equipment is the lack of automatic discrete defect classification data into multiple, significant classification bins and the lack of discrete elemental analysis data. Root cause analysis is based on minimal discrete defect analysis as a surrogate for a statistically valid sampling of defects from the bevel. This paper provides a study of the methods employed with a Hitachi RS-5500EQEQ Defect Review Scanning Electron Microscope (DRSEM) to automatically capture high resolution/high magnification images and collect elemental analysis on a statistically valid sample of the discrete defects that were located by a bevel inspection system.

  10. Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion.

    Science.gov (United States)

    Benz, Brian A; Nandadasa, Sumeda; Takeuchi, Megumi; Grady, Richard C; Takeuchi, Hideyuki; LoPilato, Rachel K; Kakuda, Shinako; Somerville, Robert P T; Apte, Suneel S; Haltiwanger, Robert S; Holdener, Bernadette C

    2016-08-01

    Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of O-fucosylation on ADAMTS9. To address this question, we compared the Pofut2 and Adamts9 knockout phenotypes and used Cre-mediated deletion of Pofut2 and Adamts9 to dissect the tissue-specific role of O-fucosylated ADAMTS9 during gastrulation. Disruption of Pofut2 using the knockout (LoxP) or gene trap (RST434) allele, as well as deletion of Adamts9, resulted in disorganized epithelia (epiblast, extraembryonic ectoderm, and visceral endoderm) and blocked mesoderm formation during gastrulation. The similarity between Pofut2 and Adamts9 mutants suggested that disruption of ADAMTS9 function could be responsible for the gastrulation defects observed in Pofut2 mutants. Consistent with this prediction, CRISPR/Cas9 knockout of POFUT2 in HEK293T cells blocked secretion of ADAMTS9. We determined that Adamts9 was dynamically expressed during mouse gastrulation by trophoblast giant cells, parietal endoderm, the most proximal visceral endoderm adjacent to the ectoplacental cone, extraembryonic mesoderm, and anterior primitive streak. Conditional deletion of either Pofut2 or Adamts9 in the epiblast rescues the gastrulation defects, and identified a new role for O-fucosylated ADAMTS9 during morphogenesis of the amnion and axial mesendoderm. Combined, these results suggested that loss of ADAMTS9 function in the extra embryonic tissue is responsible for gastrulation defects in the Pofut2 knockout. We hypothesize that loss of ADAMTS9 function in the most proximal visceral endoderm leads to slippage of

  11. Over-expression of DSCAM and COL6A2 cooperatively generates congenital heart defects.

    Directory of Open Access Journals (Sweden)

    Tamar R Grossman

    2011-11-01

    Full Text Available A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS, which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD, and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders.

  12. Atypical defects resulting in growth hormone insensitivity.

    Science.gov (United States)

    Wit, Jan M; de Luca, Francesco

    2016-06-01

    Besides four well-documented genetic causes of GH insensitivity (GHI) (GHR, STAT5B, IGF1, IGFALS defects), several other congenital and acquired conditions are associated with GHI. With respect to its anabolic actions, GH induces transcription of IGF1, IGFBP3 and IGFALS through a complex regulatory cascade including GH binding to its receptor (GHR), activation of JAK2 and phosphorylation of STAT5b, which then trafficks to the nucleus. GH also activates the MAPK and PI3K pathways. The synthesis of GHR can be reduced by estrogen deficiency or corticosteroid excess, and is possibly decreased in African pygmies. An increased degradation of GHRs because of overexpression of cytokine-inducible SH2-containing protein (CIS) was suggested for some children with idiopathic short stature. Effects on several downstream components of GH signaling were observed for FGF21, cytokines, sepsis, fever and chronic renal failure. In Noonan syndrome and other "rasopathies" the activation of the RAS-RAF-MAPK-ERK pathway leads to inhibition of the JAK/STAT pathway. In contrast, fibroblasts from tall patients with Sotos syndrome showed a downregulation of this axis. Experimental and clinical evidence suggests that the NF-κB pathway plays a role in GH signaling. In a patient with an IκBα mutation presenting with short stature, GHI, severe immune deficiency and other features, NF-κB nuclear transportation and STAT5 and PI3K expression and activity were reduced. A patient with a mosaic de novo duplication of 17q21-25 presented with several congenital anomalies, GHI and mild immunodeficiency. Studies in blood lymphocytes showed disturbed signaling of the CD28 pathway, involving NF-κB and related proteins. Functional studies on skin fibroblasts revealed that NF-κB activation, PI3K activity and STAT5 phosphorylation in response to GH were suppressed, while the sensitivity to GH in terms of MAPK phosphorylation was increased. The expression of one of the duplicated genes, PRKCA, was

  13. Zero defections: quality comes to services.

    Science.gov (United States)

    Reichheld, F F; Sasser, W E

    1990-01-01

    Companies that want to improve their service quality should take a cue from manufacturing and focus on their own kind of scrap heap: customers who won't come back. Because that scrap heap can be every bit as costly as broken parts and misfit components, service company managers should strive to reduce it. They should aim for "zero defections"--keeping every customer they can profitably serve. As companies reduce customer defection rates, amazing things happen to their financials. Although the magnitude of the change varies by company and industry, the pattern holds: profits rise sharply. Reducing the defection rate just 5% generates 85% more profits in one bank's branch system, 50% more in an insurance brokerage, and 30% more in an auto-service chain. And when MBNA America, a Delaware-based credit card company, cut its 10% defection rate in half, profits rose a whopping 125%. But defection rates are not just a measure of service quality; they are also a guide for achieving it. By listening to the reasons why customers defect, managers learn exactly where the company is falling short and where to direct their resources. Staples, the stationery supplies retailer, uses feedback from customers to pinpoint products that are priced too high. That way, the company avoids expensive broad-brush promotions that pitch everything to everyone. Like any important change, managing for zero defections requires training and reinforcement. Great-West Life Assurance Company pays a 50% premium to group health-insurance brokers that hit customer-retention targets, and MBNA America gives bonuses to departments that hit theirs. PMID:10107082

  14. Zero defections: quality comes to services.

    Science.gov (United States)

    Reichheld, F F; Sasser, W E

    1990-01-01

    Companies that want to improve their service quality should take a cue from manufacturing and focus on their own kind of scrap heap: customers who won't come back. Because that scrap heap can be every bit as costly as broken parts and misfit components, service company managers should strive to reduce it. They should aim for "zero defections"--keeping every customer they can profitably serve. As companies reduce customer defection rates, amazing things happen to their financials. Although the magnitude of the change varies by company and industry, the pattern holds: profits rise sharply. Reducing the defection rate just 5% generates 85% more profits in one bank's branch system, 50% more in an insurance brokerage, and 30% more in an auto-service chain. And when MBNA America, a Delaware-based credit card company, cut its 10% defection rate in half, profits rose a whopping 125%. But defection rates are not just a measure of service quality; they are also a guide for achieving it. By listening to the reasons why customers defect, managers learn exactly where the company is falling short and where to direct their resources. Staples, the stationery supplies retailer, uses feedback from customers to pinpoint products that are priced too high. That way, the company avoids expensive broad-brush promotions that pitch everything to everyone. Like any important change, managing for zero defections requires training and reinforcement. Great-West Life Assurance Company pays a 50% premium to group health-insurance brokers that hit customer-retention targets, and MBNA America gives bonuses to departments that hit theirs.

  15. Dermatoscopic aspects of the microphthalmia with linear skin defects (MLS) syndrome.

    Science.gov (United States)

    Almeida, Hiram Larangeira de; Rossi, Gabriela; Abreu, Luciana Boff de; Bergamaschi, Cristina; Silva, Alessandra Banaszeski da; Kutsche, Kerstin

    2014-01-01

    The association of microphthalmia and linear skin defects was named microphthalmia with linear skin defects syndrome (MLS) or MIDAS syndrome (microphthalmia, dermal aplasia, and sclerocornea), an X-chromosomal disorder manifesting mainly in females. We examined a female newborn with facial linear skin defects following the Blaschko lines. Computer tomography and ophthalmological examination confirmed bilateral microphthalmia. An interstitial microdeletion at Xp22.2, encompassing the entire HCCS gene, was identified. Dermatoscopic examination showed erythematous linear areas with telangectasias and absence of sebaceous glands, which appear as brilliant white dots. Vellus hairs were also absent in the red areas. Dermatoscopy could help to establish the diagnosis of MLS/MIDAS syndrome by confirming the aplastic nature of the lesions.

  16. Gene Therapy for Muscular Dystrophies: Progress and Challenges

    OpenAIRE

    Park, Kyung Seok; Oh, Donghoon

    2010-01-01

    Muscular dystrophies are groups of inherited progressive diseases of the muscle caused by mutations of diverse genes related to normal muscle function. Although there is no current effective treatment for these devastating diseases, various molecular strategies have been developed to restore the expressions of the associated defective proteins. In preclinical animal models, both viral and nonviral vectors have been shown to deliver recombinant versions of defective genes. Antisense oligonucle...

  17. Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-09-03

    Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntington’s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  18. A novel type of developmental dentin defect.

    Science.gov (United States)

    Lukinmaa, P L; Waltimo, J; Hölttä, P; Risteli, L; Risteli, J; Alaluusua, S

    1996-01-01

    We describe a developmental dentin disorder distinct from dentin defects characterized thus far. The proband was a 9-year-old boy who was the only family member known to be affected in five generations. The dental defect was not associated with any general disease or developmental disorder. The teeth appeared normal with the exception of the pink hue seen in some primary teeth. Radiographs showed pathological resorption of primary teeth and abnormally shaped pulp chambers and denticles in permanent teeth. Root canals were wide in developing teeth, but appeared thin in erupted teeth. Histological examination of two primary molars revealed canal-like defects in dentin. In the crown, the canals appeared as clusters, which alternated with columns of normal tubular dentin, and in the virtually atubular root dentin they were haphazardly distributed. Scanning electron microscopic examination confirmed the distribution pattern of the canals. In transmission electron microscopy, the defects were found to contain symmetrically banded, segmental collagenous structures. The canal contents immunostained with antibodies to the N-terminal propeptide of type I procollagen, suggesting retention of the propeptide extension in type I collagen. Whereas type III collagen reactivity was barely detectable in the canal region, staining for type V collagen and the non-fibril-forming type VI collagen was strong. The findings imply that the pathogenesis of the defect could be related to a local failure of odontoblasts to produce normal dentin matrix.

  19. Lattice Defects in the Kitaev Honeycomb Model.

    Science.gov (United States)

    Brennan, John; Vala, Jiří

    2016-05-19

    The Kitaev honeycomb lattice system is an important model of topological materials whose phase diagram exhibits both abelian and non-abelian topological phases. The latter, a so-called Ising phase, is related to topological superconductors. Its quasiparticle excitations, which are formed by Majorana fermions attached to vortices, show non-abelian fractional statistics and are known as Ising anyons. We investigate dislocation defects in the Ising phase of the Kitaev honeycomb model. After introducing them to the system, we accordingly generalize our solution of this model to the situation with the defects. The important part of this effort is developing an appropriate Jordan-Wigner fermionization procedure. It is expected that the presence of defects manifests itself by the formation of fermionic zero-energy modes around the defect end points. We numerically confirm this expectation and further investigate properties of these modes. The computational potential of our technique is demonstrated for both diagonalization and dynamical simulations. The latter focuses on the process of fusion of the vortex zero-energy modes with the Majorana fermions attached to the defect. This process simulates fusion of non-abelian Ising anyons. PMID:26886150

  20. Building defects in Danish construction: project characteristics influencing the occurrence of defects at handover

    DEFF Research Database (Denmark)

    Schultz, Casper Siebken; Jørgensen, Kirsten; Bonke, Sten;

    2015-01-01

    Defects in construction have gained much attention from both the public and academia. Danish construction is no exception and a number of political initiatives have been established to address the unsatisfying amounts of defects. One of the political initiatives, benchmarking, collects and provid...

  1. Transposition of the great arteries, atrial septal defect and ventricular septal defect

    OpenAIRE

    Camilleri, Ramona

    2013-01-01

    Three-day-old baby girl, transferred to NPICU because of low saturations and a development of a murmur. Following a number of rigourous test and the appropriate investigations, she was diagnosed with Transposition of the Great Arteries (TGA), a large Atrial Septal Defect, and a malaligned Ventricular Septal Defect. She was then transferred to Great Ormond Street Hospital (GOSH) for corrective surgey.

  2. Reticle defect sizing of optical proximity correction defects using SEM imaging and image analysis techniques

    Science.gov (United States)

    Zurbrick, Larry S.; Wang, Lantian; Konicek, Paul; Laird, Ellen R.

    2000-07-01

    Sizing of programmed defects on optical proximity correction (OPC) feature sis addressed using high resolution scanning electron microscope (SEM) images and image analysis techniques. A comparison and analysis of different sizing methods is made. This paper addresses the issues of OPC defect definition and discusses the experimental measurement results obtained by SEM in combination with image analysis techniques.

  3. DAG defect in Murrah buffalo bulls in Brazil

    Directory of Open Access Journals (Sweden)

    W.G. Vale

    2010-02-01

    Full Text Available Dag defect sperms have an abnormal tail coiled morphology are totally or almost totally immotile and have severe abnormalities on the fibers in the axial filament. This defect in bovine was shown to be due an autosomal recessive gene. In the present study 23 buffalo bulls age 18-34 months examined for BSE (Breeding Soundness Examination showed sperm motility varied between 0 to 70% accomplished with 10 a 65% of sperm pathology with or not a predominance of strong coiled tails with or without persistence of droplet. In Brazil Murrah breed have had only eight female PO (pure of origin - India gave origin of the herd and not more than four males where also imported from India, although in the last two decades some quantity of frozen semen were introduced in the country imported from India. As in the other domestic species inbreed seems to be the main cause of this abnormalities in different breeds. The knowledge and further study of such abnormalities is the only way to overcome a problem that if not controlled will tend to spread out without control causing in the future more problem for development of some herds.

  4. Influence of Slot Defect Length on Magnetic Flux Leakage

    Institute of Scientific and Technical Information of China (English)

    Songling HUANG; Luming LI; Haiqing YANG; Keren SHI

    2004-01-01

    A key issue, which influences the applications of magnetic flux leakage testing, is defect quantification. There have been many research on the relationship between width, depth and magnetic flux leakage of slot defect. However, the length factor is often ignored. The relationship between characteristics of defect leakage field and defect length was investigated. The magnetic flux leakages of a series of plate specimens with the same width, same depth and different length slot defects were tested under the same magnetizing conditions. Testing results show that defect length is an important parameter needed to consider in quantifying defects.

  5. Laminopathies: Multiple disorders arising from defects in nuclear architecture

    Indian Academy of Sciences (India)

    Veena K Parnaik; Kaliyaperumal Manju

    2006-09-01

    Lamins are the major structural proteins of the nucleus in an animal cell. In addition to being essential for nuclear integrity and assembly, lamins are involved in the organization of nuclear processes such as DNA replication, transcription and repair. Mutations in the human lamin A gene lead to highly debilitating genetic disorders that primarily affect muscle, adipose, bone or neuronal tissues and also cause premature ageing syndromes. Mutant lamins alter nuclear integrity and hinder signalling pathways involved in muscle differentiation and adipocyte differentiation, suggesting tissue-specific roles for lamins. Furthermore, cells expressing mutant lamins are impaired in their response to DNA damaging agents. Recent reports indicate that certain lamin mutations act in a dominant negative manner to cause nuclear defects and cellular toxicity, and suggest a possible role for aberrant lamins in normal ageing processes.

  6. Deposition-induced defect profiles in amorphous hydrogenated silicon

    OpenAIRE

    Hata, N.; Wagner, S.; Roca i Cabarrocas, P.; Favre, M.

    2008-01-01

    The thickness dependence of the subgap optical absorption in plasma-deposited hydrogenated amorphous silicon is carefully studied by photothermal deflection spectroscopy. The deep-level defect concentration decays from the top surface into the bulk where it approaches the thermal equilibrium defect density. This defect profile is interpreted in terms of the annealing, during growth, of growth-induced surface defects. It is also shown that this defect profile is compatible with the known growt...

  7. Prediction of Defective Software Modules Using Class Imbalance Learning

    OpenAIRE

    Divya Tomar; Sonali Agarwal

    2016-01-01

    Software defect predictors are useful to maintain the high quality of software products effectively. The early prediction of defective software modules can help the software developers to allocate the available resources to deliver high quality software products. The objective of software defect prediction system is to find as many defective software modules as possible without affecting the overall performance. The learning process of a software defect predictor is difficult due to the imbal...

  8. 48 CFR 1615.407-1 - Rate reduction for defective pricing or defective cost or pricing data.

    Science.gov (United States)

    2010-10-01

    ... defective pricing or defective cost or pricing data. 1615.407-1 Section 1615.407-1 Federal Acquisition... for defective pricing or defective cost or pricing data. The clause set forth in section 1652.215-70... based on a combination of cost and price analysis (community-rated)....

  9. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  10. Hovering Black Holes from Charged Defects

    CERN Document Server

    Horowitz, Gary T; Santos, Jorge E; Way, Benson

    2014-01-01

    We construct the holographic dual of an electrically charged, localised defect in a conformal field theory at strong coupling, by applying a spatially dependent chemical potential. We find that the IR behaviour of the spacetime depends on the spatial falloff of the potential. Moreover, for sufficiently localized defects with large amplitude, we find that a new gravitational phenomenon occurs: a spherical extremal charged black hole nucleates in the bulk: a hovering black hole. This is a second order quantum phase transition. We construct this new phase with several profiles for the chemical potential and study its properties. We find an apparently universal behaviour for the entropy of the defect as a function of its amplitude. We comment on the possible field theory implications of our results.

  11. Three dimensional echocardiography in congenital heart defects

    Directory of Open Access Journals (Sweden)

    Shirali Girish

    2008-01-01

    Full Text Available Three dimensional echocardiography (3DE is a new, rapidly evolving modality for cardiac imaging. Important technological advances have heralded an era where practical 3DE scanning is becoming a mainstream modality. We review the modes of 3DE that can be used. The literature has been reviewed for articles that examine the applicability of 3DE to congenital heart defects to visualize anatomy in a spectrum of defects ranging from atrioventricular septal defects to mitral valve abnormalities and Ebstein′s anomaly. The use of 3DE color flow to obtain echocardiographic angiograms is illustrated. The state of the science in quantitating right and left ventricular volumetrics is reviewed. Examples of novel applications including 3DE transesophageal echocardiography and image-guided interventions are provided. We also list the limitations of the technique, and discuss potential future developments in the field.

  12. Anomalous Coupling Between Topological Defects and Curvature

    Science.gov (United States)

    Vitelli, Vincenzo; Turner, Ari M.

    2004-11-01

    We investigate a counterintuitive geometric interaction between defects and curvature in thin layers of superfluids, superconductors, and liquid crystals deposited on curved surfaces. Each defect feels a geometric potential whose functional form is determined only by the shape of the surface, but whose sign and strength depend on the transformation properties of the order parameter. For superfluids and superconductors, the strength of this interaction is proportional to the square of the charge and causes all defects to be repelled (attracted) by regions of positive (negative) Gaussian curvature. For liquid crystals in the one elastic constant approximation, charges between 0 and 4π are attracted by regions of positive curvature while all other charges are repelled.

  13. Performance model to predict overall defect density

    Directory of Open Access Journals (Sweden)

    J Venkatesh

    2012-08-01

    Full Text Available Management by metrics is the expectation from the IT service providers to stay as a differentiator. Given a project, the associated parameters and dynamics, the behaviour and outcome need to be predicted. There is lot of focus on the end state and in minimizing defect leakage as much as possible. In most of the cases, the actions taken are re-active. It is too late in the life cycle. Root cause analysis and corrective actions can be implemented only to the benefit of the next project. The focus has to shift left, towards the execution phase than waiting for lessons to be learnt post the implementation. How do we pro-actively predict defect metrics and have a preventive action plan in place. This paper illustrates the process performance model to predict overall defect density based on data from projects in an organization.

  14. Structural control design and defective systems

    Science.gov (United States)

    Gattulli, Vincenzo; Potenza, Francesco

    2016-05-01

    The intersection between the two concepts of structural control and defectiveness is discussed. Two simple oscillators differently connected by serial spring-dashpot arrangement are used to simply simulate technically relevant cases: dissipatively coupled adjacent free-standing structures, structures equipped by TMD and base-isolated structures. Eigensolution loci of the two classes of systems are tracked against one or more significant parameters to determine the potential benefits realized by different combinations of stiffness and viscosity. In both studied cases, codimension-two manifolds in the four-parameter space corresponding to coalescing eigenvalues are determined by analytical expressions. Conditions to discern semi-simple eigenvalues from defective ones confirm that the latter is the generic case laying in a two-parameter space while the former span a one-parameter subspace. The knowledge of the location of the defective systems in the parameter space permits to determine regions with specific dynamical properties useful for control design purpose.

  15. Artificial defects detection and location during welding

    International Nuclear Information System (INIS)

    Welding control by acoustic emission allows defects detection as soon as they are created. Acoustic testing saves time and gives better quality assurance in the case of multiple pass welding of plates. A welded joint was performed on A533B steel plates 250 mm thick by submerged arc welding. Artificial defects were implanted to determine significative parameters of acoustic reception. In operating conditions a significant acoustic activity takes place only during welding as shown by preliminary tests. At the same time an important noise is created by the arc, scories cooling and metal solidification and cooling. These problems are solved by an original processing in time-space detecting and locating defects with a good approximation

  16. Study of point defect detectors in Si

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The importance of point defects in semiconductor and functionmaterials has been studied indetail, but effective means for detecting point defects has not been available for a long time.Theend of range defects in Si, produced by 140 keV Ge+ implantation,were investigated as detectorsfor measuring the interstitial concentration created by 42 keV B+ implantation.The concentrationof interstitial resulting from the B+ implantation and the behaviorof the interstitial flux underdifferent annealing condition were given. The enhanced diffusion in the borondoped EPI marker,resulting from mobile non-equilibrium interstitials wasdemonstrated to be transient. Interstitialfluxes arising from processing can be detected bytransient enhanced diffusion (TED) of dopedmarker layers as well.

  17. Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1

    Directory of Open Access Journals (Sweden)

    Ullmann Reinhard

    2011-08-01

    Full Text Available Abstract Background Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. Methods 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. Results By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. Conclusions We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not

  18. Understanding the causes and prevention of neural tube defects: Insights from the splotch mouse model.

    Science.gov (United States)

    Greene, Nicholas D E; Massa, Valentina; Copp, Andrew J

    2009-04-01

    Splotch mutant mice develop neural tube defects (NTDs), comprising exencephaly and/or spina bifida, as well as neural crest-related defects and abnormalities of limb musculature. Defects in splotch mice result from mutations in Pax3, and some human NTDs may also result from mutations in the human PAX3 gene. Pax3 encodes a transcription factor whose function may influence expression of multiple downstream genes associated with a variety of cellular properties (including apoptosis, adhesion, proliferation, and differentiation), that could be important for neural tube closure. The frequency of NTDs varies between mutant alleles and is also influenced by genetic background and environmental factors. Notably, splotch provides a model for folic acid-preventable NTDs, and conversely, dietary folate deficiency exacerbates NTDs. Understanding the molecular and cellular basis of splotch NTDs, as well as the mechanisms by which the frequency of defects is influenced by genetic and environmental factors (such as sub-optimal folate status), may provide insight into the causation of these severe congenital malformations in humans.

  19. DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects.

    Science.gov (United States)

    Kessler, Kristin; Wunderlich, Ina; Uebe, Steffen; Falk, Nathalie S; Gießl, Andreas; Brandstätter, Johann Helmut; Popp, Bernt; Klinger, Patricia; Ekici, Arif B; Sticht, Heinrich; Dörr, Helmuth-Günther; Reis, André; Roepman, Ronald; Seemanová, Eva; Thiel, Christian T

    2015-01-01

    Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we performed exome sequencing and identified compound heterozygous missense and nonsense mutations in DYNC2LI1 segregating with the phenotype. DYNC2LI1 is ubiquitously expressed and interacts with DYNC2H1 to form the dynein-2 complex important for retrograde IFT. Using DYNC2LI1 siRNA knockdown in fibroblasts we identified a significantly reduced cilia length proposed to affect cilia function. In addition, depletion of DYNC2LI1 induced altered cilia morphology with broadened ciliary tips and accumulation of IFT-B complex proteins in accordance with retrograde IFT defects. Our results expand the clinical spectrum of ciliopathies caused by defects of the dynein-2 complex.

  20. Gauge theory and defects in solids

    CERN Document Server

    Edelen, DGB

    2012-01-01

    This new series Mechanics and Physics of Discrete Systems aims to provide a coherent picture of the modern development of discrete physical systems. Each volume will offer an orderly perspective of disciplines such as molecular dynamics, crystal mechanics and/or physics, dislocation, etc. Emphasized in particular are the fundamentals of mechanics and physics that play an essential role in engineering applications.Volume 1, Gauge Theory and Defects in Solids, presents a detailed development of a rational theory of the dynamics of defects and damage in solids. Solutions to field e

  1. Paternal age and offspring congenital heart defects

    DEFF Research Database (Denmark)

    Su, Xiu Juan; Yuan, Wei; Huang, Guo Ying;

    2015-01-01

    Paternal age has been associated with offspring congenital heart defects (CHDs), which might be caused by increased mutations in the germ cell line because of cumulated cell replications. Empirical evidences, however, remain inconclusive. Furthermore, it is unknown whether all subtypes of CHDs are.......17-2.43). We observed similar results when subanalyses were restricted to children born to mothers of 27-30 years old. After taking into consideration of maternal age, our data suggested that advanced paternal age was associated with an increased prevalence of one subtype of offspring congenital heart defects...

  2. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1988-01-01

    Thirteen patients with medullary sponge kidney underwent a short ammonium chloride loading test to investigate their renal acidification capacity. All but 1 presented with a history of recurrent renal calculi and showed bilateral widespread renal medullary calcification on X-ray examination. Nine...... patients had some form of renal acidification defect; 8 had the distal type of renal tubular acidosis, 2 the complete and 6 the incomplete form. One patient had proximal renal tubular acidosis. These findings, which suggest that renal acidification defects play an important role in the pathogenesis...... of renal calculi in medullary sponge kidney, have considerable therapeutic implications....

  3. Defects and diffusion in semiconductors XIV

    CERN Document Server

    Fisher, David J

    2012-01-01

    This 14th volume in the series covers the latest results in the field of Defects and Diffusion in Semiconductor. The issue also includes some original papers: An Experimental Study of the Thermal Properties of Modified 9Cr-1Mo Steel; Physico-Mechanical Properties of Sintered Iron-Silica Sand Nanoparticle Composites: A Preliminary Study; Defect and Dislocation Density Parameters of 5251 Al Alloy Using Positron Annihilation Lifetime Technique; A Novel Computational Strategy to Enhance the Ability of Elaborate Search by Entire Swarm to Find the Best Solution in Optimization of AMCs; Synthesis and

  4. Quantum computing with defects in diamond

    International Nuclear Information System (INIS)

    Full text: Single spins in semiconductors, in particular associated with defect centers, are promising candidates for practical and scalable implementation of quantum computing even at room temperature. Such an implementation may also use the reliable and well known gate constructions from bulk nuclear magnetic resonance (NMR) quantum computing. Progress in development of quantum processor based on defects in diamond will be discussed. By combining optical microscopy, and magnetic resonance techniques, the first quantum logical operations on single spins in a solid are now demonstrated. The system is perspective for room temperature operation because of a weak dependence of decoherence on temperature (author)

  5. Automatic leather inspection of defective patterns

    Science.gov (United States)

    Tafuri, Maria; Branca, Antonella; Attolico, Giovanni; Distante, Arcangelo; Delaney, William

    1996-02-01

    Constant and consistent quality levels in the manufacturing industry increasingly require automatic inspection. This paper describes a vision system for leather inspection based upon visual textural properties of the material surface. As visual appearances of both leather and defects exhibit a wide range of variations due to original skin characteristics, curing processes and defect causes, location and classification of defective areas become hard tasks. This paper describes a method for separating the oriented structures of defects from normal leather, a background not homogeneous in color, thickness, brightness and finally in wrinkledness. The first step requires the evaluation of the orientation field from the image of the leather. Such a field associates to each point of the image a 2D vector having as direction the dominant local orientation of gradient vectors and the length proportional to their coherence evaluated in a neighborhood of fixed size. The second step analyzes such a vector flow field by projecting it on a set of basis vectors (elementary texture vectors) spanning the vector space where the vector fields associated to the defects can be defined. The coefficients of these projections are the parameters by means of which both detection and classification can be performed. Since the set of basis vectors is neither orthogonal nor complete, the projection requires the definition of a global optimization criteria that has been chosen to be the minimum difference between the original flow field and the vector field obtained as a linear combination of the basis vectors using the estimated coefficients. This optimization step is performed through a neural network initialized to recognize a limited number of patterns (corresponding to the basis vectors). This second step estimates the parameter vector in each point of the original image. Both leather without defects and defects can be characterized in terms of coefficient vectors making it possible to

  6. Lecture notes on 2-dimensional defect TQFT

    CERN Document Server

    Carqueville, Nils

    2016-01-01

    These notes offer an introduction to the functorial and algebraic description of 2-dimensional topological quantum field theories `with defects', assuming only superficial familiarity with closed TQFTs in terms of commutative Frobenius algebras. The generalisation of this relation is a construction of pivotal 2-categories from defect TQFTs. We review this construction in detail, flanked by a range of examples. Furthermore we explain how open/closed TQFTs are equivalent to Calabi-Yau categories and the Cardy condition, and how to extract such data from pivotal 2-categories.

  7. DIAGNOSIS OF PITCH AND LOAD DEFECTS

    DEFF Research Database (Denmark)

    2009-01-01

    The invention relates to a method, system and computer readable code for diagnosis of pitch and/or load defects of e.g. wind turbines as well as wind turbines using said diagnosis method and/or comprising said diagnosis system.......The invention relates to a method, system and computer readable code for diagnosis of pitch and/or load defects of e.g. wind turbines as well as wind turbines using said diagnosis method and/or comprising said diagnosis system....

  8. Defect dynamics in crystalline buckled membranes

    Science.gov (United States)

    Pezzutti, Aldo D.; Vega, Daniel A.

    2011-07-01

    We study the dynamics of defect annihilation in flexible crystalline membranes suffering a symmetry-breaking phase transition. The kinetic process leading the system toward equilibrium is described through a Brazovskii-Helfrich-Canham Hamiltonian. In membranes, a negative disclination has a larger energy than a positive disclination. Here we show that this energetic asymmetry does not only affect equilibrium properties, like the Kosterlitz-Thouless transition temperature, but also plays a fundamental role in the dynamic of defects. Both unbinding of dislocations and Carraro-Nelson “antiferromagnetic” interactions between disclinations slow down the dynamics below the Lifshitz-Safran regime observed in flat hexagonal systems.

  9. Dirac oscillator interacting with a topological defect

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, J.; Furtado, C.; Moraes, F. [Unidade Academica de Tecnologia de Alimentos, CCTA, Universidade Federal de Campina Grande, Pereiros, 58840-000, Pombal, Paraiba (Brazil); Departamento de Fisica, CCEN, Universidade Federal da Paraiba, Cidade Universitaria, 58051-970 Joao Pessoa, Paraiba (Brazil)

    2011-09-15

    In this work we study the interaction problem of a Dirac oscillator with gravitational fields produced by topological defects. The energy levels of the relativistic oscillator in the cosmic string and in the cosmic dislocation space-times are sensible to curvature and torsion associated to these defects and are important evidence of the influence of the topology on this system. In the presence of a localized magnetic field the energy levels acquire a term associated with the Aharonov-Bohm effect. We obtain the eigenfunctions and eigenvalues and see that in the nonrelativistic limit some results known in standard quantum mechanics are reached.

  10. GaN: Defect and Device Issues

    Energy Technology Data Exchange (ETDEWEB)

    Pearton, S.J.; Ren, F.; Shul, R.J.; Zolper, J.C.

    1998-11-09

    The role of extended and point defects, and key impurities such as C, O and H, on the electrical and optical properties of GaN is reviewed. Recent progress in the development of high reliability contacts, thermal processing, dry and wet etching techniques, implantation doping and isolation and gate insulator technology is detailed. Finally, the performance of GaN-based electronic and photonic devices such as field effect transistors, UV detectors, laser diodes and light-emitting diodes is covered, along with the influence of process-induced or grown-in defects and impurities on the device physics.

  11. Thermal Defects of Avionic Turbojet Engines

    Directory of Open Access Journals (Sweden)

    Szczepankowski Andrzej

    2016-08-01

    Full Text Available The paper analyzes the most frequent reasons associated with operation of avionic turbojet engines (ATE and leading to initiation of thermal defects affecting turbine units. These reasons are illustrated with examples of gradual deteriorations revealed on surfaces of turbine parts and subassemblies and defected during endoscopic examinations of propelling drives. Attention is paid to various design and technological improvements that are implemented to counteract such deteriorations. The analysis is focused on mistakes that are committed during operation, repairs or manufacturing of avionic turbojet engines and that may affect safety of aircraft operations.

  12. Diagnosis and treatment of congenital heart defects

    International Nuclear Information System (INIS)

    The Clinic for Congenital Heart Defects in Bad Oeynhausen, Germany, specializes in the interdisciplinary care of children and adolescents with congenital heart defects. The available expertise covers all aspects of diagnosis and treatment, as well as clinical research at the highest level. The clinic has a complete array of imaging systems, including a Philips Integris BV5000 Biplane cath lab system, Philips Gyroscan Intera CV MR system, ultrasound and PET systems. The range of available equipment makes it possible to select the most appropriate imaging modality for each situation, with particular reference to the need to minimize the overall radiation exposure. (orig.)

  13. Assessment of fuel defects in Darlington NGS

    International Nuclear Information System (INIS)

    This paper outlines a safety analysis of the defect status of Darlington-1 during the operating period August to October 1991. The models used are outlined, and their implementation is described. The results of the analysis indicate that the number of defected fuel elements never exceeded three in the north primary heat transport loop, and the mass of tramp uranium was ∼2 grams during the period in question. These results are within Ontario Hydro's experience with new reactors. 6 refs., 3 figs., 2 tabs

  14. Toward defect guard-banding of EUV exposures by full chip optical wafer inspection of EUV mask defect adders

    Science.gov (United States)

    Halle, Scott D.; Meli, Luciana; Delancey, Robert; Vemareddy, Kaushik; Crispo, Gary; Bonam, Ravi; Burkhardt, Martin; Corliss, Daniel

    2015-03-01

    The detection of EUV mask adder defects has been investigated with an optical wafer defect inspection system employing a methodology termed Die-to-"golden" Virtual Reference Die (D2VRD). Both opaque and clear type mask absorber programmed defects were inspected and characterized over a range of defect sizes, down to (4x mask) 40 nm. The D2VRD inspection system was capable of identifying the corresponding wafer print defects down to the limit of the defect printability threshold at approximately 30 nm (1x wafer). The efficacy of the D2VRD scheme on full chip wafer inspection to suppress random process defects and identify real mask defects is demonstrated. Using defect repeater analysis and patch image classification of both the reference die and the scanned die enables the unambiguous identification of mask adder defects.

  15. DNA-transporting nanoparticles : design and in vitro evaluation of DNA and formulation for non-viral gene delivery

    NARCIS (Netherlands)

    van Gaal, E.V.B.

    2010-01-01

    The aim of gene therapy is to treat, cure or prevent a disease by replacing defective genes, introducing new genes or changing the expression of a person’s genes. Success of gene therapy is dependent on successful delivery of DNA from the site of administration into cell nuclei. Naturally occurring

  16. AAV vectors as gene delivery vehicles in the central nervous system

    NARCIS (Netherlands)

    Broekman, M.L.D.

    2006-01-01

    Recombinant gene delivery vehicles based on the replication-defective AAV have gained a preeminent position in the field of gene delivery to the brain. Efficient global gene delivery to the CNS is beneficial for the study of gene products is the entire CNS as well as for introducing and expressing g

  17. Blaschko Linear Enamel Defects - A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia

    Directory of Open Access Journals (Sweden)

    Stefan Gysin

    2015-05-01

    Full Text Available Focal dermal hypoplasia (FDH is a rare genetic skin disorder. The inheritance of FDH or Goltz-Gorlin syndrome is X-linked dominant and the disease is associated with a PORCN gene mutation. This gene plays a key role in the Wnt pathway, which has an impact on embryonic development. Every tissue derived from meso- and ectoderm can be affected. Patients suffer from cutaneous, ocular, osseous, oral and dental defects. The skin and dental alterations manifest along the Blaschko lines. We present a woman (born in 1962 suffering from FDH with congenital skin changes and Blaschko linear enamel defects. Typical symptoms (e.g. fat herniations, scoliosis, syndactyly, microphthalmia, caries and alopecia plus vertical grooving of all teeth gave a first indication. Molecular genetic testing confirmed the definitive diagnosis of FDH. We hypothesize that, in the context of typical skin changes, visible Blaschko lines on the teeth in the form of vertical grooves are almost pathognomonic for FDH.

  18. Variations in programmed phase defect size and its impact on defect detection signal intensity using at-wavelength inspection system

    Science.gov (United States)

    Amano, Tsuyoshi; Takagi, Noriaki; Abe, Tsukasa

    2015-10-01

    A programmed phase defect Extreme Ultraviolet (EUV) mask was fabricated and measurement repeatability of the defect size using a scanning probe microscope (SPM) was evaluated. The SPM measurement results indicated that the defect size variation as registered by the measurement repeatability were much smaller than the defect-to-defect variations. It means the defect-to-defect variation in size actually does exist. Some defects were found where their sizes before a multilayer coating (on quartz) were all the same but after the coat their sizes varied quite significantly when observed on the multilayer. This result indicated that it is difficult to estimate the phase defect size on quartz, whereas they can be accurately measured on multilayer. Influences of the defect size variation on defect detection signal intensity (DSI) using an actinic blank inspection (ABI) system were examined; their influences on the wafer printability were also examined. The DSI was strongly correlated with defect depth on the multilayer, and it was also indicated that the ABI can detect small variations in defect sizes. It was also confirmed that the impact of the phase defects on wafer printed CDs were proportional to the DSIs, and that the ABI has a potential to detect phase defect that could cause 5 % of the CD error when printing 16 nm dense lines.

  19. Parental mental illness and fatal birth defects in a national birth cohort

    DEFF Research Database (Denmark)

    Webb, Roger; Pickles, A.R.; King-Hele, Sarah;

    2007-01-01

    BACKGROUND: Few large studies describe links between maternal mental illness and risk of major birth defect in offspring. Evidence is sparser still for how effects vary between maternal diagnoses and no previous study has assessed risk with paternal illnesses.MethodA population-based birth cohort...... genetic effects directly linked with maternal illness, lifestyle factors (diet, smoking, alcohol and drugs), poor antenatal care, psychotropic medication toxicity, and gene-environment interactions. Further research is needed to elucidate the causal mechanisms...

  20. Production of Replication-Defective Retrovirus by Transient Transfection of 293T cells

    OpenAIRE

    Gavrilescu, L Cristina; Richard A Van Etten

    2007-01-01

    Our lab studies human myeloproliferative diseases induced by such oncogenes as Bcr-Abl or growth factor receptor-derived oncogenes (ZNF198-FGFR1, Bcr-PDGFRα, etc.). We are able to model and study a human-like disease in our mouse model, by transplanting bone marrow cells previously infected with a retrovirus expressing the oncogene of interest. Replication-defective retrovirus encoding a human oncogene and a marker (GFP, RFP, antibiotic resistance gene, etc.) is produced by a transient transf...