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Sample records for chk1 haploinsufficiency results

  1. Nuclear Chk1 prevents premature mitotic entry.

    Science.gov (United States)

    Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki

    2011-07-01

    Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry.

  2. Nuclear Chk1 prevents premature mitotic entry.

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    Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki

    2011-07-01

    Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry. PMID:21628425

  3. Chk1 suppressed cell death

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    Meuth Mark

    2010-09-01

    Full Text Available Abstract The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1.

  4. Tumour growth environment modulates Chk1 signalling pathways and Chk1 inhibitor sensitivity

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    Massey, Andrew J.

    2016-01-01

    Clinical development of Chk1 inhibitors is currently focussed on evaluating activity as monotherapy and as potentiators of chemotherapy. To aid translation of pre-clinical studies, we sought to understand the effects of the tumour growth environment on Chk1 signalling and sensitivity to small molecule Chk1 inhibition. Spheroid culture altered Chk1 signalling to a more xenograft like state but decreased sensitivity to Chk1 inhibition. Growth in low serum did not alter DDR signalling but increased the sensitivity of A2058 and U2OS tumour cells to Chk1 inhibition. An analysis of the expression levels of replication associated proteins identified a correlation between Cdc6 and pChk1 (S296) as well as total Chk1 in xenograft derived samples and between Cdc6 and total Chk1 in anchorage-dependent growth derived protein samples. No apparent correlation between Chk1 or Cdc6 expression and sensitivity to Chk1 inhibition in vitro was observed. A database analysis revealed upregulation of CDC6 mRNA expression in tumour compared to normal tissue and a correlation between CDC6 and CHEK1 mRNA expression in human cancers. We suggest that Cdc6 overexpression in human tumours requires a concomitant increase in Chk1 to counterbalance the deleterious effects of origin hyperactivation-induced DNA damage. PMID:27775084

  5. Chk1 prevents abnormal mitosis of S-phase HeLa cells containing DNA damage

    Institute of Scientific and Technical Information of China (English)

    LI XiaoFang; WARD Tarsha; YAO XueBiao; WU JiaRui

    2009-01-01

    To explore effects of DNA damage on cell-cycle progression in p53-deficient tumor cells,synchronized HeLa cells at G1,S and G2/M phases were treated with methyl methanesulfnate (MMS).The results showed that the MMS treatment resulted in the cell-cycle arrest or delay in all 3 phases,while the S-phase cells were the most sensitive to MMS.Further studies demonstrated that ATM-Chk2 and p38 MAPK signaling pathways were activated in all 3 phases when the cells were treated with MMS;whereas Chk1 was activated only in S phase under the drug treatment,indicating that Chk1 specifically participated in S-phase checkpoints.To analyze the role of Chk1 in S-phase checkpoints,we administered a specific Chk1 inhibitor,UCN-01,to the S-phase cells.The results showed that the S-phase cells treated with MMS+UCN-01 could enter aberrant mitosis without finishing DNA replication,indicating that Chk1 mainly functions in the DNA damage checkpoint rather than in the replication checkpoint.In addition,MMS treatment alone inhibited the accumulation of cyclin B1,a key component of M-phase CDK-cyclin complex,in the S-phase cells,whereas the inhibition of Chk1 activation resulted in the accumulation of cyclin B1 in the MMS-treated S-phase cells.This observation further supports the view that DNA-damaged S-phase cells enter abnormal mitosis when Chk1 activation is inhibited.Our results demonstrate that Chk1 is a specific kinase that plays an important role in the MMS-induced S-phase DNA damage checkpoint.As p53 is not involved in this process,Chk1 may be a potential target for p53-deficient tumor therapy.

  6. Phosphorylation-dependent interactions between Crb2 and Chk1 are essential for DNA damage checkpoint.

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    Meng Qu

    2012-07-01

    Full Text Available In response to DNA damage, the eukaryotic genome surveillance system activates a checkpoint kinase cascade. In the fission yeast Schizosaccharomyces pombe, checkpoint protein Crb2 is essential for DNA damage-induced activation of downstream effector kinase Chk1. The mechanism by which Crb2 mediates Chk1 activation is unknown. Here, we show that Crb2 recruits Chk1 to double-strand breaks (DSBs through a direct physical interaction. A pair of conserved SQ/TQ motifs in Crb2, which are consensus phosphorylation sites of upstream kinase Rad3, is required for Chk1 recruitment and activation. Mutating both of these motifs renders Crb2 defective in activating Chk1. Tethering Crb2 and Chk1 together can rescue the SQ/TQ mutations, suggesting that the main function of these phosphorylation sites is promoting interactions between Crb2 and Chk1. A 19-amino-acid peptide containing these SQ/TQ motifs is sufficient for Chk1 binding in vitro when one of the motifs is phosphorylated. Remarkably, the same peptide, when tethered to DSBs by fusing with either recombination protein Rad22/Rad52 or multi-functional scaffolding protein Rad4/Cut5, can rescue the checkpoint defect of crb2Δ. The Rad22 fusion can even bypass the need for Rad9-Rad1-Hus1 (9-1-1 complex in checkpoint activation. These results suggest that the main role of Crb2 and 9-1-1 in DNA damage checkpoint signaling is recruiting Chk1 to sites of DNA lesions.

  7. Targeted Radiosensitization by the Chk1 Inhibitor SAR-020106

    Energy Technology Data Exchange (ETDEWEB)

    Borst, Gerben R., E-mail: g.borst@nki.nl [The Institute of Cancer Research, London (United Kingdom); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); McLaughlin, Martin; Kyula, Joan N.; Neijenhuis, Sari; Khan, Aadil; Good, James; Zaidi, Shane [The Institute of Cancer Research, London (United Kingdom); Powell, Ned G. [HPV Research Group, School of Medicine, Cardiff University, Cardiff (United Kingdom); Meier, Pascal; Collins, Ian; Garrett, Michelle D. [The Institute of Cancer Research, London (United Kingdom); Verheij, Marcel [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Harrington, Kevin J. [The Institute of Cancer Research, London (United Kingdom)

    2013-03-15

    Purpose: To explore the activity of a potent Chk1 inhibitor (SAR-020106) in combination with radiation. Methods and Materials: Colony and mechanistic in vitro assays and a xenograft in vivo model. Results: SAR-020106 suppressed-radiation-induced G{sub 2}/M arrest and reduced clonogenic survival only in p53-deficient tumor cells. SAR-020106 promoted mitotic entry following irradiation in all cell lines, but p53-deficient cells were likely to undergo apoptosis or become aneuploid, while p53 wild-type cells underwent a postmitotic G{sub 1} arrest followed by subsequent normal cell cycle re-entry. Following combined treatment with SAR-020106 and radiation, homologous-recombination-mediated DNA damage repair was inhibited in all cell lines. A significant increase in the number of pan-γH2AX-staining apoptotic cells was observed only in p53-deficient cell lines. Efficacy was confirmed in vivo in a clinically relevant human head-and-neck cell carcinoma xenograft model. Conclusion: The Chk1 inhibitor SAR-020106 is a potent radiosensitizer in tumor cell lines defective in p53 signaling.

  8. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage

    DEFF Research Database (Denmark)

    Syljuåsen, Randi G; Sørensen, Claus Storgaard; Hansen, Lasse Tengbjerg;

    2005-01-01

    -nuclear phosphorylation of histone H2AX, p53, Smc1, replication protein A, and Chk1 itself in human S-phase cells. These phosphorylations were inhibited by ATR siRNA and caffeine, but they occurred independently of ATM. Chk1 inhibition also caused an increased initiation of DNA replication, which was accompanied by...... increased amounts of nonextractable RPA protein, formation of single-stranded DNA, and induction of DNA strand breaks. Moreover, these responses were prevented by siRNA-mediated downregulation of Cdk2 or the replication initiation protein Cdc45, or by addition of the CDK inhibitor roscovitine. We propose...... that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage. These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use in...

  9. Inhibition of autophagy enhances DNA damage-induced apoptosis by disrupting CHK1-dependent S phase arrest

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    Liou, Jong-Shian; Wu, Yi-Chen; Yen, Wen-Yen; Tang, Yu-Shuan [Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, ROC (China); Kakadiya, Rajesh B.; Su, Tsann-Long [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, ROC (China); Yih, Ling-Huei, E-mail: lhyih@gate.sinica.edu.tw [Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, ROC (China)

    2014-08-01

    DNA damage has been shown to induce autophagy, but the role of autophagy in the DNA damage response and cell fate is not fully understood. BO-1012, a bifunctional alkylating derivative of 3a-aza-cyclopenta[a]indene, is a potent DNA interstrand cross-linking agent with anticancer activity. In this study, BO-1012 was found to reduce DNA synthesis, inhibit S phase progression, and induce phosphorylation of histone H2AX on serine 139 (γH2AX) exclusively in S phase cells. Both CHK1 and CHK2 were phosphorylated in response to BO-1012 treatment, but only depletion of CHK1, but not CHK2, impaired BO-1012-induced S phase arrest and facilitated the entry of γH2AX-positive cells into G2 phase. CHK1 depletion also significantly enhanced BO-1012-induced cell death and apoptosis. These results indicate that BO-1012-induced S phase arrest is a CHK1-dependent pro-survival response. BO-1012 also resulted in marked induction of acidic vesicular organelle (AVO) formation and microtubule-associated protein 1 light chain 3 (LC3) processing and redistribution, features characteristic of autophagy. Depletion of ATG7 or co-treatment of cells with BO-1012 and either 3-methyladenine or bafilomycin A1, two inhibitors of autophagy, not only reduced CHK1 phosphorylation and disrupted S phase arrest, but also increased cleavage of caspase-9 and PARP, and cell death. These results suggest that cells initiate S phase arrest and autophagy as pro-survival responses to BO-1012-induced DNA damage, and that suppression of autophagy enhances BO-1012-induced apoptosis via disruption of CHK1-dependent S phase arrest. - Highlights: • Autophagy inhibitors enhanced the cytotoxicity of a DNA alkylating agent, BO-1012. • BO-1012-induced S phase arrest was a CHK1-dependent pro-survival response. • Autophagy inhibition enhanced BO-1012 cytotoxicity via disrupting the S phase arrest.

  10. Inhibition of autophagy enhances DNA damage-induced apoptosis by disrupting CHK1-dependent S phase arrest

    International Nuclear Information System (INIS)

    DNA damage has been shown to induce autophagy, but the role of autophagy in the DNA damage response and cell fate is not fully understood. BO-1012, a bifunctional alkylating derivative of 3a-aza-cyclopenta[a]indene, is a potent DNA interstrand cross-linking agent with anticancer activity. In this study, BO-1012 was found to reduce DNA synthesis, inhibit S phase progression, and induce phosphorylation of histone H2AX on serine 139 (γH2AX) exclusively in S phase cells. Both CHK1 and CHK2 were phosphorylated in response to BO-1012 treatment, but only depletion of CHK1, but not CHK2, impaired BO-1012-induced S phase arrest and facilitated the entry of γH2AX-positive cells into G2 phase. CHK1 depletion also significantly enhanced BO-1012-induced cell death and apoptosis. These results indicate that BO-1012-induced S phase arrest is a CHK1-dependent pro-survival response. BO-1012 also resulted in marked induction of acidic vesicular organelle (AVO) formation and microtubule-associated protein 1 light chain 3 (LC3) processing and redistribution, features characteristic of autophagy. Depletion of ATG7 or co-treatment of cells with BO-1012 and either 3-methyladenine or bafilomycin A1, two inhibitors of autophagy, not only reduced CHK1 phosphorylation and disrupted S phase arrest, but also increased cleavage of caspase-9 and PARP, and cell death. These results suggest that cells initiate S phase arrest and autophagy as pro-survival responses to BO-1012-induced DNA damage, and that suppression of autophagy enhances BO-1012-induced apoptosis via disruption of CHK1-dependent S phase arrest. - Highlights: • Autophagy inhibitors enhanced the cytotoxicity of a DNA alkylating agent, BO-1012. • BO-1012-induced S phase arrest was a CHK1-dependent pro-survival response. • Autophagy inhibition enhanced BO-1012 cytotoxicity via disrupting the S phase arrest

  11. A kinome screen identifies checkpoint kinase 1 (CHK1 as a sensitizer for RRM1-dependent gemcitabine efficacy.

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    Jun Zhou

    Full Text Available Gemcitabine is among the most efficacious and widely used antimetabolite agents. Its molecular targets are ribonucleotide reductase M1 (RRM1 and elongating DNA. Acquired and de novo resistance as a result of RRM1 overexpression are major obstacles to therapeutic efficacy. We deployed a synthetic lethality screen to investigate if knockdown of 87 selected protein kinases by siRNA could overcome RRM1-dependent gemcitabine resistance in high and low RRM1-expressing model systems. The models included genetically RRM1-modified lung and breast cancer cell lines, cell lines with gemcitabine-induced RRM1 overexpression, and a series of naturally gemcitabine-resistant cell lines. Lead molecular targets were validated by determination of differential gemcitabine activity using cell lines with and without target knock down, and by assessing synergistic activity between gemcitabine and an inhibitor of the lead target. CHK1 was identified has the kinase with the most significant and robust interaction, and it was validated using AZD7762, a small-molecule ATP-competitive inhibitor of CHK1 activation. Synergism between CHK1 inhibition and RRM1-dependent gemcitabine efficacy was observed in cells with high RRM1 levels, while antagonism was observed in cells with low RRM1 levels. In addition, four cell lines with natural gemcitabine resistance demonstrated improved gemcitabine efficacy after CHK1 inhibition. In tumor specimens from 187 patients with non-small-cell lung cancer, total CHK1 and RRM1 in situ protein levels were significantly (p = 0.003 and inversely correlated. We conclude that inhibition of CHK1 may have its greatest clinical utility in malignancies where gemcitabine resistance is a result of elevated RRM1 levels. We also conclude that CHK1 inhibition in tumors with low RRM1 levels may be detrimental to gemcitabine efficacy.

  12. Unique functions of CHK1 and WEE1 underlie synergistic anti-tumor activity upon pharmacologic inhibition

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    Guertin Amy D

    2012-11-01

    Full Text Available Abstract Background Inhibition of kinases involved in the DNA damage response sensitizes cells to genotoxic agents by abrogating checkpoint-induced cell cycle arrest. CHK1 and WEE1 act in a pathway upstream of CDK1 to inhibit cell cycle progression in response to damaged DNA. Therapeutic targeting of either CHK1 or WEE1, in combination with chemotherapy, is under clinical evaluation. These studies examine the overlap and potential for synergy when CHK1 and WEE1 are inhibited in cancer cell models. Methods Small molecules MK-8776 and MK-1775 were used to selectively and potently inhibit CHK1 and WEE1, respectively. Results In vitro, the combination of MK-8776 and MK-1775 induces up to 50-fold more DNA damage than either MK-8776 or MK-1775 alone at a fixed concentration. This requires aberrant cyclin-dependent kinase activity but does not appear to be dependent on p53 status alone. Furthermore, DNA damage takes place primarily in S-phase cells, implying disrupted DNA replication. When dosed together, the combination of MK-8776 and MK-1775 induced more intense and more durable DNA damage as well as anti-tumor efficacy than either MK-8776 or MK-1775 dosed alone. DNA damage induced by the combination was detected in up to 40% of cells in a treated xenograft tumor model. Conclusions These results highlight the roles of WEE1 and CHK1 in maintaining genomic integrity. Importantly, the strong synergy observed upon inhibition of both kinases suggests unique yet complimentary anti-tumor effects of WEE1 and CHK1 inhibition. This demonstration of DNA double strand breaks in the absence of a DNA damaging chemotherapeutic provides preclinical rationale for combining WEE1 and CHK1 inhibitors as a cancer treatment regimen.

  13. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer.

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    Xu, J; Li, Y; Wang, F; Wang, X; Cheng, B; Ye, F; Xie, X; Zhou, C; Lu, W

    2013-02-21

    MicroRNAs (miRNAs) act as important gene regulators in human genomes and their aberrant expression links to many malignancies. We previously identified a different characteristic miRNA expression profile in cervical cancer from that in cervical normal tissues, including the downregulated miR-424. However, the role and mechanism of miR-424 in cervical cancer still remain unknown. Here, we focused on identifying the tumor-suppressive function and clinical significance of miR-424 and exploring the mechanistic relevance by characterizing its target. We showed a significantly decreased expression of miR-424 in 147 cervical cancer tissues versus 74 cervical normal tissues by performing quantitative RT-PCR. In 147 cervical cancer tissue samples, low-level expression of miR-424 was positively correlated with poor tumor differentiation, advanced clinical stage, lymph node metastasis and other poor prognostic clinicopathological parameters. Further in vitro observations showed that enforced expression of miR-424 inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, and suppressed cell migration and invasion in two human cervical cancer cell lines, SiHa and CaSki, implying that miR-424 functions as a tumor suppressor in the progression of cervical cancer. Interestingly, overexpression of miR-424 inhibited the expression of protein checkpoint kinase 1 (Chk1) and phosphorylated Chk1 (p-Chk1) at residues Ser345 and decreased the activity of luciferase-reporter containing the 3'-untranslated region (UTR) of Chk1 with predicted miR-424-binding site. Moreover, miR-424 expression levels were inversely correlated with Chk1 and p-Chk1 protein levels in both cervical cancer and normal tissues. Furthermore, RNAi-mediated knockdown of Chk1 decreased matrix metalloproteinase 9 expression and phenocopied the tumor suppressive effects of miR-424 in cell models. Taken together, our results identify a crucial tumor suppressive role of miR-424 in the progression of

  14. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation

    DEFF Research Database (Denmark)

    Gatei, Magtouf; Sloper, Katie; Sørensen, Claus Storgaard;

    2003-01-01

    . In mammalian cells, evidence has been presented that Chk1 is devoted to the ATR signaling pathway and is modified by ATR in response to replication inhibition and UV-induced damage, whereas Chk2 functions primarily through ATM in response to ionizing radiation (IR), suggesting that Chk2 and Chk1 might have......In mammals, the ATM (ataxia-telangiectasia-mutated) and ATR (ATM and Rad3-related) protein kinases function as critical regulators of the cellular DNA damage response. The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2....... Phosphorylation of Chk1 on Ser-317 in response to IR is ATM-dependent. We also show that functional NBS1 is required for phosphorylation of Chk1, indicating that NBS1 might facilitate the access of Chk1 to ATM at the sites of DNA damage. Abrogation of Chk1 expression by RNA interference resulted in defects in IR-induced...

  15. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair

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    Sørensen, Claus Storgaard; Hansen, Lasse Tengbjerg; Dziegielewski, Jaroslaw;

    2005-01-01

    The essential checkpoint kinase Chk1 is required for cell-cycle delays after DNA damage or blocked DNA replication. However, it is unclear whether Chk1 is involved in the repair of damaged DNA. Here we establish that Chk1 is a key regulator of genome maintenance by the homologous recombination......, the essential recombination repair protein RAD51 is recruited to DNA repair foci performing a vital role in correct HRR. We demonstrate that Chk1 interacts with RAD51, and that RAD51 is phosphorylated on Thr 309 in a Chk1-dependent manner. Consistent with a functional interplay between Chk1 and RAD51...

  16. Clonning and expression analysis of Chk1 gene in Daphnia pulex%蚤状溞(Daphnia pulex)Chk1基因的克隆与表达分析

    Institute of Scientific and Technical Information of China (English)

    方增冰; 戴新宇; 邹秀; 郭晓鸽; 徐善良; 王丹丽; 赵云龙

    2015-01-01

    The full-length cDNA of a Chk1 (DpChk1) was cloned from cladoceran Daphnia pulex using rapid amplification of comple-mentary DNA ends ( RACE) method.The DpChk1 cDNA is 1767 bp in length;and it has a 1497-bp open reading frame that encodes a 498-amino-acid polypeptide containing three conserved Ser-Gln (SQ), and Thr-Gln (TQ) sequence.In addition, DpChk1 shared homology of 51%-55% with gene in Rhipicephalus pulchellus, Megachile rotundata, Metaseiulus occidentalis, Acyrthosiphon pisum and Drosophila melanogaster.Phylogenetic analysis revealed that DpChk 1 protein has a close genetic relationship with Phylum arthropo-da such as Acyrthosiphon pisum, Megachile rotundata, Drosophila melanogaster, Rhipicephalus pulchellus, Metaseiulus occidenat lis and so on.qPCR results (real-time quantitative PCR) showed that the DpChk1 expression was significantly higher (P<0.05) in ephippial female than in parthenogenetic female and was the lowest in the resting egg .Therefore, Chk1 was closely related to the reproduction conversion of Daphnia pulex.%用RACE技术从蚤状溞( Daphnia pulex)中克隆到Chk1基因cDNA全长为1767 bp,开放阅读框为1497 bp,编码了498个氨基酸,其结构中存在3个保守的Ser-Gln ( SQ)和Thr-Gln ( TQ)序列。同源性比对结果显示,蚤状溞Chk1基因与丽色扇头蜱、切叶蜂、转基因捕食螨、豌豆长管蚜和黑腹果蝇等的同源性均为51%~55%。进化分析发现,蚤状溞Chk1基因与豌豆长管蚜、切叶蜂、黑腹果蝇、丽色扇头蜱和转基因捕食螨等节肢动物亲缘关系最近。Real Time PCR实验结果表明,Chk1 mRNA在两性溞的表达量显著高于孤雌溞( P<0.05),且在休眠卵中表达量最低。推测Chk1基因可能在蚤状溞的生殖转化调控中发挥重要作用。

  17. A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1

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    Blasius, Melanie; Forment, Josep V; Thakkar, Neha;

    2011-01-01

    BACKGROUND: The cell-cycle checkpoint kinase Chk1 is essential in mammalian cells due to its roles in controlling processes such as DNA replication, mitosis and DNA-damage responses. Despite its paramount importance, how Chk1 controls these functions remains unclear, mainly because very few Chk1...

  18. HPV-positive HNSCC cell lines but not primary human fibroblasts are radiosensitized by the inhibition of Chk1

    International Nuclear Information System (INIS)

    Purpose: Despite the comparably high cure rates observed for HPV-positive HNSCC, there is still a great need for specific tumor radiosensitization due to the often severe side effects resulting from intense radiochemotherapy. We recently demonstrated that HPV-positive HNSCC cell lines are characterized by a defect in DNA double-strand break repair associated with a pronounced G2-arrest. Here we tested whether abrogation of this radiation-induced G2-arrest by the inhibition of Chk1 results in specific radiosensitization of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV and p16-positive (93-VU-147T, UM-SCC-47, UT-SCC-45, UD-SCC-2, UPCI-SCC-154) and two HPV and p16-negative HNSCC cell lines, as well as two normal human fibroblast strains. Chk1 was inhibited by the selective inhibitor PF-00477736. Cell cycle distribution was determined by flow cytometry, Chk1-activity via Western blot and cell survival by colony formation assay. Results: With the exception of UPCI-SCC-154, the inhibition of Chk1 was found to abolish the pronounced radiation-induced G2-arrest in all HPV-positive cells utilized. All tumor cell lines that demonstrated the abrogation of G2-arrest also demonstrated radiosensitization. Notably, in G1-arrest-proficient normal human fibroblasts no radiosensitization was induced. Conclusion: Abrogation of the G2 checkpoint through the inhibition of Chk1 may be used to selectively increase the cellular radiosensitivity of HPV-positive HNSCC without affecting the surrounding normal tissue

  19. The radioresistance to killing of A1-5 cells derives from activation of the Chk1 pathway

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    Hu, B.; Zhou, X. Y.; Wang, X.; Zeng, Z. C.; Iliakis, G.; Wang, Y.

    2001-01-01

    Checkpoints respond to DNA damage by arresting the cell cycle to provide time for facilitating repair. In mammalian cells, the G(2) checkpoint prevents the Cdc25C phosphatase from removing inhibitory phosphate groups from the mitosis-promoting kinase Cdc2. Both Chk1 and Chk2, the checkpoint kinases, can phosphorylate Cdc25C and inactivate its in vitro phosphatase activity. Therefore, both Chk1 and Chk2 are thought to regulate the activation of the G(2) checkpoint. Here we report that A1-5, a transformed rat embryo fibroblast cell line, shows much more radioresistance associated with a much stronger G(2) arrest response when compared with its counterpart, B4, although A1-5 and B4 cells have a similar capacity for nonhomologous end-joining DNA repair. These phenotypes of A1-5 cells are accompanied by a higher Chk1 expression and a higher phosphorylation of Cdc2. On the other hand, Chk2 expression increases slightly following radiation; however, it has no difference between A1-5 and B4 cells. Caffeine or UCN-01 abolishes the extreme radioresistance with the strong G(2) arrest and at the same time reduces the phosphorylation of Cdc2 in A1-5 cells. In addition, Chk1 but not Chk2 antisense oligonucleotide sensitizes A1-5 cells to radiation-induced killing and reduces the G(2) arrest of the cells. Taken together these results suggest that the Chk1/Cdc25C/Cdc2 pathway is the major player for the radioresistance with G(2) arrest in A1-5 cells.

  20. The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions

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    Geneviève Rodier

    2015-04-01

    Full Text Available Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.

  1. The transcription factor E4F1 coordinates CHK1-dependent checkpoint and mitochondrial functions.

    Science.gov (United States)

    Rodier, Geneviève; Kirsh, Olivier; Baraibar, Martín; Houlès, Thibault; Lacroix, Matthieu; Delpech, Hélène; Hatchi, Elodie; Arnould, Stéphanie; Severac, Dany; Dubois, Emeric; Caramel, Julie; Julien, Eric; Friguet, Bertrand; Le Cam, Laurent; Sardet, Claude

    2015-04-14

    Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.

  2. The nucleolus stress response is coupled to an ATR-Chk1-mediated G2 arrest.

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    Ma, Hanhui; Pederson, Thoru

    2013-05-01

    We report experiments on the connection between nucleolar stress and cell cycle progression, using HeLa cells engineered with the fluorescent ubiquitinylation-based cell cycle indicator. Nucleolar stress elicited by brief exposure of cells to a low concentration of actinomycin D that selectively inhibits rRNA synthesis had no effect on traverse of G1 or S, but stalled cells in very late interphase. Additional experiments revealed that a switch occurs during a specific temporal window during nucleolar stress and that the subsequent cell cycle arrest is not triggered simply by the stress-induced decline in the synthesis of rRNA or by a ribosome starvation phenomenon. Further experiments revealed that this nucleolus stress-induced cell cycle arrest involves the action of a G2 checkpoint mediated by the ataxia telangiectasia and Rad3-related protein (ATR)-checkpoint kinase 1 (Chk1) pathway. Based on analysis of the cell cycle stages at which this nucleolar stress effect is put into action, to become manifest later, our results demonstrate a feedforward mechanism that leads to G2 arrest and identify ATR and Chk1 as molecular agents of the requisite checkpoint.

  3. Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress

    Science.gov (United States)

    Du, Zhanwen; Gao, Jinnan; Yang, Shuming; Gorityala, Shashank; Xiong, Xiahui; Deng, Ou; Ma, Zhefu; Yan, Chunhong; Susana, Gonzalo; Xu, Yan; Zhang, Junran

    2016-01-01

    Radiotherapy (RT) remains a standard therapeutic modality for breast cancer patients. However, intrinsic or acquired resistance limits the efficacy of RT. Here, we demonstrate that CHK1 inhibitor AZD7762 alone significantly inhibited the growth of radioresistant breast cancer cells (RBCC). Given the critical role of ATR/CHK1 signaling in suppressing oncogene-induced replication stress (RS), we hypothesize that CHK1 inhibition leads to the specific killing for RBCC due to its abrogation in the suppression of RS induced by oncogenes. In agreement, the expression of oncogenes c-Myc/CDC25A/c-Src/H-ras/E2F1 and DNA damage response (DDR) proteins ATR/CHK1/BRCA1/CtIP were elevated in RBCC. AZD7762 exposure led to significantly higher levels of RS in RBCC, compared to the parental cells. The mechanisms by which CHK1 inhibition led to specific increase of RS in RBCC were related to the interruptions in the replication fork dynamics and the homologous recombination (HR). In summary, RBCC activate oncogenic pathways and thus depend upon mechanisms controlled by CHK1 signaling to maintain RS under control for survival. Our study provided the first example where upregulating RS by CHK1 inhibitor contributes to the specific killing of RBCC, and highlight the importance of the CHK1 as a potential target for treatment of radioresistant cancer cells. PMID:27167194

  4. Inhibition of Chk1 by CEP-3891 accelerates mitotic nuclear fragmentation in response to ionizing Radiation

    DEFF Research Database (Denmark)

    Syljuåsen, Randi G; Sørensen, Claus Storgaard; Nylandsted, Jesper;

    2004-01-01

    The human checkpoint kinase Chk1 has been suggested as a target for cancer treatment. Here, we show that a new inhibitor of Chk1 kinase, CEP-3891, efficiently abrogates both the ionizing radiation (IR)-induced S and G(2) checkpoints. When the checkpoints were abrogated by CEP-3891, the majority (64...

  5. Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yu; Liu Qiao; Liu Zhaojian; Li Boxuan; Sun Zhaoliang; Zhou Haibin; Zhang Xiyu; Gong Yaoqin [Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan (China); Shao Changshun, E-mail: changshun.shao@gmail.com [Ministry of Education Key Laboratory of Experimental Teratology and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan (China)

    2012-06-01

    Berberine has been shown to possess anti-tumor activity against a wide spectrum of cancer cells. It inhibits cancer cell proliferation by inducing cell cycle arrest, at G1 and/or G2/M, and apoptosis. While it has been documented that berberine induces G1 arrest by activating the p53-p21 cascade, it remains unclear what mechanism underlies the berberine-induced G2/M arrest, which is p53-independent. In this study, we tested the anti-proliferative effect of berberine on murine prostate cancer cell line RM-1 and characterized the underlying mechanisms. Berberine dose-dependently induced DNA double-strand breaks and apoptosis. At low concentrations, berberine was observed to induce G1 arrest, concomitant with the activation of p53-p21 cascade. Upon exposure to berberine at a higher concentration (50 {mu}M) for 24 h, cells exhibited G2/M arrest. Pharmacological inhibition of ATM by KU55933, or Chk1 by UCN-01, could efficiently abrogate the G2/M arrest in berberine-treated cells. Downregulation of Chk1 by RNA interference also abolished the G2/M arrest caused by berberine, confirming the role of Chk1 in the pathway leading to G2/M arrest. Abrogation of G2/M arrest by ATM inhibition forced more cells to undergo apoptosis in response to berberine treatment. Chk1 inhibition by UCN-01, on the other hand, rendered cells more sensitive to berberine only when p53 was inhibited. Our results suggest that combined administration of berberine and caffeine, or other ATM inhibitor, may accelerate the killing of cancer cells.

  6. Characterization of a mantle cell lymphoma cell line resistant to the Chk1 inhibitor PF-00477736.

    Science.gov (United States)

    Restelli, Valentina; Chilà, Rosaria; Lupi, Monica; Rinaldi, Andrea; Kwee, Ivo; Bertoni, Francesco; Damia, Giovanna; Carrassa, Laura

    2015-11-10

    Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by the chromosomal translocation t(11;14) that leads to constitutive expression of cyclin D1, a master regulator of the G1-S phase. Chk1 inhibitors have been recently shown to be strongly effective as single agents in MCL. To investigate molecular mechanisms at the basis of Chk1 inhibitor activity, a MCL cell line resistant to the Chk1 inhibitor PF-00477736 (JEKO-1 R) was obtained and characterized. The JEKO-1 R cell line was cross resistant to another Chk1 inhibitor (AZD-7762) and to the Wee1 inhibitor MK-1775. It displayed a shorter doubling time than parental cell line, likely due to a faster S phase. Cyclin D1 expression levels were decreased in resistant cell line and its re-overexpression partially re-established PF-00477736 sensitivity. Gene expression profiling showed an enrichment in gene sets involved in pro-survival pathways in JEKO-1 R. Dasatinib treatment partly restored PF-00477736 sensitivity in resistant cells suggesting that the pharmacological interference of pro-survival pathways can overcome the resistance to Chk1 inhibitors. These data further corroborate the involvement of the t(11;14) in cellular sensitivity to Chk1 inhibitors, fostering the clinical testing of Chk1 inhibitors as single agents in MCL. PMID:26439697

  7. Expression of Chk1 in Primary Liver Cancer and Liver Non-tumor Tissue%Chk1在原发性肝癌和肝非肿瘤组织中的表达

    Institute of Scientific and Technical Information of China (English)

    马瑞波; 杨大刚; 孙诚谊; 王众

    2012-01-01

    目的:探讨细胞周期检测点启动DNA损伤修复的主要激酶Chk1蛋白在肝非肿瘤组织和原发性肝癌组织中的表达差异、以及与临床病理特征之间的关系.方法:应用免疫组织化学法检测15例肝非肿瘤组织(其中正常肝组织7例、肝硬化组织8例)和41例原发性肝癌组织Chk1蛋白的表达.结果:Chk1蛋白在原发性肝癌组织中表达阳性率为73.2%,在肝非肿瘤组织中表达阳性率为26.7%差异有统计学意义(P<0.05) ;Chk1蛋白在不同分化程度的原发性肝癌患者中的表达有差异,有统计学意义(P<0.05).结论:Chk1在原发性肝癌中高表达可能与原发性肝癌的发生、发展有关.%To investigate the expression difference of Chkl protien in primary liver cancer and non-tumor liver tissue, and to explore the probable relationship between its expression and clini-copathologic features of liver cancer. Methods: Immunohistochemistry was applied to detect the expressions of Chkl in 15 cases with liver non-tumor tissue (7 cases with normal liver tissue, 8 cases with cirrhosis tissue) and 41 cases with primary liver cancer with various differentiation degrees. Results : The positive expression rate of Chkl in primary liver cancer (73. 2% ) was higher than that of non-tumor liver tissue (26.1% ) {P <0. 05}. Significant differences were found in Chkl expressions among primary liver cancer with various differentiation degrees ( P < 0. 05 ). Conclusions: The high expression level of Chkl in primary liver cancer indicates that Chkl may be related to genesis and progression of primary liver cancer.

  8. STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell proliferation.

    Science.gov (United States)

    Koganti, Siva; Hui-Yuen, Joyce; McAllister, Shane; Gardner, Benjamin; Grasser, Friedrich; Palendira, Umaimainthan; Tangye, Stuart G; Freeman, Alexandra F; Bhaduri-McIntosh, Sumita

    2014-04-01

    DNA damage response (DDR) is a signaling network that senses DNA damage and activates response pathways to coordinate cell-cycle progression and DNA repair. Thus, DDR is critical for maintenance of genome stability, and presents a powerful defense against tumorigenesis. Therefore, to drive cell-proliferation and transformation, viral and cellular oncogenes need to circumvent DDR-induced cell-cycle checkpoints. Unlike in hereditary cancers, mechanisms that attenuate DDR and disrupt cell-cycle checkpoints in sporadic cancers are not well understood. Using Epstein-Barr virus (EBV) as a source of oncogenes, we have previously shown that EBV-driven cell proliferation requires the cellular transcription factor STAT3. EBV infection is rapidly followed by activation and increased expression of STAT3, which mediates relaxation of the intra-S phase cell-cycle checkpoint; this facilitates viral oncogene-driven cell proliferation. We now show that replication stress-associated DNA damage, which results from EBV infection, is detected by DDR. However, signaling downstream of ATR is impaired by STAT3, leading to relaxation of the intra-S phase checkpoint. We find that STAT3 interrupts ATR-to-Chk1 signaling by promoting loss of Claspin, a protein that assists ATR to phosphorylate Chk1. This loss of Claspin which ultimately facilitates cell proliferation is mediated by caspase 7, a protein that typically promotes cell death. Our findings demonstrate how STAT3, which is constitutively active in many human cancers, suppresses DDR, fundamental to tumorigenesis. This newly recognized role for STAT3 in attenuation of DDR, discovered in the context of EBV infection, is of broad interest as the biology of cell proliferation is central to both health and disease.

  9. CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy.

    Science.gov (United States)

    Barker, Holly E; Patel, Radhika; McLaughlin, Martin; Schick, Ulrike; Zaidi, Shane; Nutting, Christopher M; Newbold, Katie L; Bhide, Shreerang; Harrington, Kevin J

    2016-09-01

    Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a standard-of-care for locally advanced head and neck cancer but is frequently ineffective. Research into enhancing radiation responses as a means of improving treatment outcomes represents a high priority. Here, we evaluated a CHK1 inhibitor (CCT244747) as a radiosensitiser and investigated whether a mechanistically rational triple combination of radiation/paclitaxel/CHK1 inhibitor delivered according to an optimized schedule would provide added benefit. CCT244747 abrogated radiation-induced G2 arrest in the p53-deficient HNSCC cell lines, HN4 and HN5, causing cells to enter mitosis with unrepaired DNA damage. The addition of paclitaxel further increased cell kill and significantly reduced tumor growth in an HN5 xenograft model. Importantly, a lower dose of paclitaxel could be used when CCT244747 was included, therefore potentially limiting toxicity. Triple therapy reduced the expression of several markers of radioresistance. Moreover, the more radioresistant HN5 cell line exhibited greater radiation-mediated CHK1 activation and was more sensitive to triple therapy than HN4 cells. We analyzed CHK1 expression in a panel of head and neck tumors and observed that primary tumors from HPV(+) patients, who went on to recur postradiotherapy, exhibited significantly stronger expression of total, and activated CHK1. CHK1 may serve as a biomarker for identifying tumors likely to recur and, therefore, patients who may benefit from concomitant treatment with a CHK1 inhibitor and paclitaxel during radiotherapy. Clinical translation of this strategy is under development. Mol Cancer Ther; 15(9); 2042-54. ©2016 AACR.

  10. miR-107 activates ATR/Chk1 pathway and suppress cervical cancer invasion by targeting MCL1.

    Directory of Open Access Journals (Sweden)

    Chengyan Zhou

    Full Text Available MicroRNAs (miRNAs are a class of single-stranded, non-coding RNAs of about 22 nucleotides in length. Increasing evidence implicates miRNAs may function as oncogenes or tumor suppressors. Here we showed that miR-107 directly targeted MCL1 and activated ATR/Chk1 pathway to inhibit proliferation, migration and invasiveness of cervical cancer cells. Moreover, we found that MCL1 was frequently up-regulated in cervical cancer, and knockdown of MCL1 markedly inhibited cancer cell proliferation, migration and invasion, whereas ectopic expression of MCL1 significantly enhances these properties. The restoration of MCL1 expression can counteract the effect of miR-107 on the cancer cells. Together, miR-107 is a new regulator of MCL1, and both miR-107 and MCL1 play important roles in the pathogenesis of cervical cancer. We have therefore identified a mechanism for ATR/Chk1 pathway which involves an increase in miR-107 leading to a decrease in MCL1. Correspondingly, our results revealed that miR-107 affected ATR/Chk1 signalling and gene expression, and implicated miR-107 as a therapeutic target in human cervical cancer. We also demonstrated that taxol attenuated migration and invasion in cervical cancer cells by activating the miR-107, in which miR-107 play an important role in regulating the expression of MCL1. Elucidation of this discovered MCL1 was directly regulated by miR-107 will greatly enhance our understanding of the mechanisms responsible for cervical cancer and will provide an additional arm for the development of anticancer therapies.

  11. Suppression of allelic recombination and aneuploidy by cohesin is independent of Chk1 in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Shay Covo

    Full Text Available Sister chromatid cohesion (SCC, which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC. In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC. Nonetheless, here we show that, unlike SCC mutations, loss of CHK1 did not increase spontaneous or damage-induced allelic recombination or aneuploidy. We suggest that Chk1 has a redundant role in the control of DIC or that DIC is redundant for maintaining genome stability.

  12. Suppression of Allelic Recombination and Aneuploidy by Cohesin Is Independent of Chk1 in Saccharomyces cerevisiae

    Science.gov (United States)

    Gordenin, Dmitry A.; Resnick, Michael A.

    2014-01-01

    Sister chromatid cohesion (SCC), which is established during DNA replication, ensures genome stability. Establishment of SCC is inhibited in G2. However, this inhibition is relived and SCC is established as a response to DNA damage, a process known as Damage Induced Cohesion (DIC). In yeast, Chk1, which is a kinase that functions in DNA damage signal transduction, is considered an activator of SCC through DIC. Nonetheless, here we show that, unlike SCC mutations, loss of CHK1 did not increase spontaneous or damage-induced allelic recombination or aneuploidy. We suggest that Chk1 has a redundant role in the control of DIC or that DIC is redundant for maintaining genome stability. PMID:25551702

  13. NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Melixetian, Marina; Klein, Ditte Kjaersgaard;

    2010-01-01

    The DNA damage induced G(2)/M checkpoint is an important guardian of the genome that prevents cell division when DNA lesions are present. The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator. CDC25A proteolysis is controlled by direct phosphorylation events...... is required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. The activity of NEK11 is in turn controlled by CHK1 that activates NEK11 via phosphorylation on serine 273. Since inhibition of NEK11 activity forces checkpoint-arrested cells into mitosis and cell death, NEK11 is, like CHK1...

  14. Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint.

    Directory of Open Access Journals (Sweden)

    Junchao Duan

    Full Text Available Silica nanoparticles have become promising carriers for drug delivery or gene therapy. Endothelial cells could be directly exposed to silica nanoparticles by intravenous administration. However, the underlying toxic effect mechanisms of silica nanoparticles on endothelial cells are still poorly understood. In order to clarify the cytotoxicity of endothelial cells induced by silica nanoparticles and its mechanisms, cellular morphology, cell viability and lactate dehydrogenase (LDH release were observed in human umbilical vein endothelial cells (HUVECs as assessing cytotoxicity, resulted in a dose- and time- dependent manner. Silica nanoparticles-induced reactive oxygen species (ROS generation caused oxidative damage followed by the production of malondialdehyde (MDA as well as the inhibition of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px. Both necrosis and apoptosis were increased significantly after 24 h exposure. The mitochondrial membrane potential (MMP decreased obviously in a dose-dependent manner. The degree of DNA damage including the percentage of tail DNA, tail length and Olive tail moment (OTM were markedly aggravated. Silica nanoparticles also induced G2/M arrest through the upregulation of Chk1 and the downregulation of Cdc25C, cyclin B1/Cdc2. In summary, our data indicated that the toxic effect mechanisms of silica nanoparticles on endothelial cells was through DNA damage response (DDR via Chk1-dependent G2/M checkpoint signaling pathway, suggesting that exposure to silica nanoparticles could be a potential hazards for the development of cardiovascular diseases.

  15. Sensitization of human cancer cells to gemcitabine by the Chk1 inhibitor MK-8776: cell cycle perturbation and impact of administration schedule in vitro and in vivo

    International Nuclear Information System (INIS)

    addition of MK-8776 enhances sensitivity to gemcitabine: first, there is an increased number of cells arrested in S phase; and second, the arrested cells have adequate time to initiate recombination and thereby become Chk1 dependent. These results have important implications for the design of clinical trials using this drug combination

  16. Defective DNA repair increases susceptibility to senescence through extension of Chk1-mediated G2 checkpoint activation.

    Science.gov (United States)

    Johmura, Yoshikazu; Yamashita, Emiri; Shimada, Midori; Nakanishi, Keiko; Nakanishi, Makoto

    2016-01-01

    Susceptibility to senescence caused by defective DNA repair is a major hallmark of progeroid syndrome patients, but molecular mechanisms of how defective DNA repair predisposes to senescence are largely unknown. We demonstrate here that suppression of DNA repair pathways extends the duration of Chk1-dependent G2 checkpoint activation and sensitizes cells to senescence through enhancement of mitosis skipping. Extension of G2 checkpoint activation by introduction of the TopBP1 activation domain and the nondegradable mutant of Claspin sensitizes cells to senescence. In contrast, a shortening of G2 checkpoint activation by expression of SIRT6 or depletion of OTUB2 reduces susceptibility to senescence. Fibroblasts from progeroid syndromes tested shows a correlation between an extension of G2 checkpoint activation and an increase in the susceptibility to senescence. These results suggest that extension of G2 checkpoint activation caused by defective DNA repair is critical for senescence predisposition in progeroid syndrome patients. PMID:27507734

  17. A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition

    Science.gov (United States)

    Gill, Martin R.; Harun, Siti Norain; Halder, Swagata; Boghozian, Ramon A.; Ramadan, Kristijan; Ahmad, Haslina; Vallis, Katherine A.

    2016-08-01

    Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)]2+ (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)]2+ before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.

  18. A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition.

    Science.gov (United States)

    Gill, Martin R; Harun, Siti Norain; Halder, Swagata; Boghozian, Ramon A; Ramadan, Kristijan; Ahmad, Haslina; Vallis, Katherine A

    2016-01-01

    Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing. PMID:27558808

  19. Circumvention of Mcl-1-Dependent Drug Resistance by Simultaneous Chk1 and MEK1/2 Inhibition in Human Multiple Myeloma Cells

    Science.gov (United States)

    Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E.; Sanderson, Michael W.; Bodie, Wesley W.; Kramer, Lora B.; Orlowski, Robert Z.; Grant, Steven

    2014-01-01

    The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM. PMID:24594907

  20. Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Xin-Yan Pei

    Full Text Available The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

  1. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

    DEFF Research Database (Denmark)

    Sørensen, Claus Storgaard; Syljuåsen, Randi G; Falck, Jacob;

    2003-01-01

    Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A...

  2. A balanced pyrimidine pool is required for optimal Chk1 activation to prevent ultrafine anaphase bridge formation.

    Science.gov (United States)

    Gemble, Simon; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Biard, Denis; Lambert, Sarah; Amor-Guéret, Mounira

    2016-08-15

    Cytidine deaminase (CDA) deficiency induces an excess of cellular dCTP, which reduces basal PARP-1 activity, thereby compromising complete DNA replication, leading to ultrafine anaphase bridge (UFB) formation. CDA dysfunction has pathological implications, notably in cancer and in Bloom syndrome. It remains unknown how reduced levels of PARP-1 activity and pyrimidine pool imbalance lead to the accumulation of unreplicated DNA during mitosis. We report that a decrease in PARP-1 activity in CDA-deficient cells impairs DNA-damage-induced Chk1 activation, and, thus, the downstream checkpoints. Chemical inhibition of the ATR-Chk1 pathway leads to UFB accumulation, and we found that this pathway was compromised in CDA-deficient cells. Our data demonstrate that ATR-Chk1 acts downstream from PARP-1, preventing the accumulation of unreplicated DNA in mitosis, and, thus, UFB formation. Finally, delaying entry into mitosis is sufficient to prevent UFB formation in both CDA-deficient and CDA-proficient cells, suggesting that both physiological and pathological UFBs are derived from unreplicated DNA. Our findings demonstrate an unsuspected requirement for a balanced nucleotide pool for optimal Chk1 activation both in unchallenged cells and in response to genotoxic stress.

  3. The regulatory beta-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1

    DEFF Research Database (Denmark)

    Kreutzer, Jan Nicolas; Guerra, Barbara

    2007-01-01

    Human CDC25 phosphatases play an important role in cell cycle regulation by removing inhibitory phosphate groups on cyclin-CDKs. Chk1 has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct mechanisms. The kinase activity of Chk1 is evident...... cell cycle progression is shown to enhance CDC25A degradation, and this occurs in a manner similar to that by which CDC25A is down-regulated upon activation of cellular checkpoint responses. By using RNA interference to specifically deplete cells of Chk1, we demonstrate that Chk1 mediates the down-regulation...... cell cycle regulation and indicate the mechanism by which CDC25A turnover might be regulated by Chk1 in the absence of DNA damage....

  4. Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM–Chk1/2–Cdc25C pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Yong-Cheng [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Su, Nan [Department of Quality Detection and Management, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan (China); Shi, Xiao-Jing; Zhao, Wen; Ke, Yu [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China); Zi, Xiaolin [Department of Urology, University of California, Irvine, Orange, CA (United States); Department of Pharmacology, University of California, Irvine, Orange, CA (United States); Department of Pharmaceutical Sciences, University of California, Irvine, Orange, CA (United States); Zhao, Ning-Min; Qin, Yu-Hua; Zhao, Hong-Wei [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Liu, Hong-Min, E-mail: liuhm@zzu.edu.cn [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China)

    2015-01-15

    Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM–Chk1/2–Cdc25C pathway. - Highlights: • Jaridonin induced G2/M phase arrest through induction of redox imbalance. • Jaridonin increased the level of ROS through depleting glutathione in cell. • ATM–Chk1/2–Cdc25C were involved in Jaridonin-induced cell cycle arrest. • Jaridonin selectively inhibited cancer cell viability and cell cycle progression.

  5. Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage.

    Science.gov (United States)

    Inoue, Yasumichi; Kitagawa, Masatoshi; Taya, Yoichi

    2007-04-18

    The retinoblastoma tumor suppressor protein (pRB) plays a critical role in the control of cell proliferation and in the DNA damage checkpoints. pRB inhibits cell cycle progression through interactions with the E2F family of transcription factors. Here, we report that DNA damage induced not only the dephosphorylation of pRB at Cdk phosphorylation sites and the binding of pRB to E2F-1, but also the phosphorylation of pRB at Ser612. Phosphorylation of pRB at Ser612 enhanced the formation of a complex between pRB and E2F-1. Substitution of Ser612 with Ala decreased pRB-E2F-1 binding and the transcriptional repression activity. Until now, Ser612 of pRB has been thought to be phosphorylated by Cdk2. However, the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage, and inhibition of ATM-Chk1/2 activity suppressed the phosphorylation of Ser612 and the binding of pRB to E2F-1. These results suggest that Ser612 is phosphorylated by Chk1/2 after DNA damage, leading to the formation of pRB-E2F-1. This is the first report that pRB is phosphorylated in vivo by a kinase other than Cdk.

  6. Munc18-1 haploinsufficiency results in enhanced anxiety-like behavior as determined by heart rate responses in mice.

    Science.gov (United States)

    Hager, Torben; Maroteaux, Grégoire; Pont, Paula du; Julsing, Joris; van Vliet, Rick; Stiedl, Oliver

    2014-03-01

    Heterozygous (HZ) missense mutations in the gene encoding syntaxin binding protein 1 (Stxbp1 or Munc18-1), a presynaptic protein essential for neurotransmitter release, causes early infantile epileptic encephalopathy, abnormal brain structure and mental retardation in humans. Here we investigated whether the mouse model mimics symptoms of the human phenotype. The effects of the deletion of munc18-1 were studied in HZ and wild-type (WT) mice based on heart rate (HR) and its variability (HRV) as independent measures to expand previous behavioral results of enhanced anxiety and impaired emotional learning suggesting mild cognitive impairments. HR responses were assessed during novelty exposure, during the expression and extinction of conditioned tone-dependent fear and during the diurnal phase. Novelty exposure yielded no differences in activity patterns between the two genotypes, while maximum HR differed significantly (WT: 770 bpm; HZ: 790 bpm). Retention tests after both auditory delay and trace fear conditioning showed a delayed extinction of the conditioned HR response in HZ mice compared to WT mice. Since the HR versus HRV correlation and HR dynamics assessed by nonlinear methods revealed similar function in HZ and WT mice, the higher HR responses of munc18-1 HZ mice to different emotional challenges cannot be attributed to differences in autonomic nervous system function. Thus, in contrast to the adverse consequences of deletion of a single allele of munc18-1 in humans, C57BL/6J mice show enhanced anxiety responses based on HR adjustments that extend previous results on the behavioral level without support of cognitive impairment, epileptic seizures and autonomic dysregulation.

  7. Staurosporine is chemoprotective by inducing G1 arrest in a Chk1- and pRb-dependent manner.

    Science.gov (United States)

    Murray, Mollianne McGahren; Bui, Tuyen; Smith, Michelle; Bagheri-Yarmand, Rozita; Wingate, Hannah; Hunt, Kelly K; Keyomarsi, Khandan

    2013-10-01

    Chemotherapeutic agents have been the mainstay of cancer therapy for years. However, their effectiveness has been limited by toxicities they impart on normal cells. Staurosporine (ST) has been shown to arrest normal, but not breast cancer, cells in G1. Therefore, ST may become a chemoprotective agent, arresting normal cells while allowing tumor cells to enter cell cycle phases where they are sensitive to chemotherapeutic agents. Understanding the mechanism of ST-mediated G1 arrest may allow for a beneficial chemoprotective treatment strategy for patients. We utilized 76NE6 (pRb+/p53-), 76NF2V (pRb+/p53+) and 76NE7 (pRb-/P53+) non-tumorigenic human mammary epithelial cell lines to understand the role of the Rb and p53 pathways in ST-directed G1 arrest. CDK4 was downregulated by ST in Rb+ cells, but its presence could not reverse the arrest, neither did its stable downregulation alter ST-mediated cellular response. ST-mediated G1 arrest required pRb, which in turn initiated a cascade of events leading to inhibition of CDK4. Further assessment of this pathway revealed that Chk1 expression and activity were required for the Rb-dependent arrest. For example, pRb+ cells with small interfering RNA to Chk1 had approximately 60% less cells in G1 phase compared with controls and pRb- cells do not arrest upon ST. Furthermore, Chk1 expression facilitates the release of the Rb+ cells from G1 arrest. Collectively, our data suggest that pRb cooperates with Chk1 to mediate a G1 arrest only in pRb+ cells. The elucidation of this pathway can help identify novel agents to protect cancer patients against the debilitating effects of chemotherapy.

  8. A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase.

    Science.gov (United States)

    Sakurikar, Nandini; Thompson, Ruth; Montano, Ryan; Eastman, Alan

    2016-01-12

    DNA damage activates Checkpoint kinase 1 (Chk1) to halt cell cycle progression thereby preventing further DNA replication and mitosis until the damage has been repaired. Consequently, Chk1 inhibitors have emerged as promising anticancer therapeutics in combination with DNA damaging drugs, but their single agent activity also provides a novel approach that may be particularly effective in a subset of patients. From analysis of a large panel of cell lines, we demonstrate that 15% are very sensitive to the Chk1 inhibitor MK-8776. Upon inhibition of Chk1, sensitive cells rapidly accumulate DNA double-strand breaks in S phase in a CDK2- and cyclin A-dependent manner. In contrast, resistant cells can continue to grow for at least 7 days despite continued inhibition of Chk1. Resistance can be circumvented by inhibiting Wee1 kinase and thereby directly activating CDK2. Hence, sensitivity to Chk1 inhibition is regulated upstream of CDK2 and correlates with accumulation of CDC25A. We conclude that cells poorly tolerate CDK2 activity in S phase and that a major function of Chk1 is to ensure it remains inactive. Indeed, inhibitors of CDK1 and CDK2 arrest cells in G1 or G2, respectively, but do not prevent progression through S phase demonstrating that neither kinase is required for S phase progression. Inappropriate activation of CDK2 in S phase underlies the sensitivity of a subset of cell lines to Chk1 inhibitors, and this may provide a novel therapeutic opportunity for appropriately stratified patients. PMID:26595527

  9. ATR-Chk1-APC/C-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

    DEFF Research Database (Denmark)

    Yamada, M.; Watanabe, K.; Mistrik, M.;

    2013-01-01

    replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosomeCdh1 (APC/C) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C through...... degradation of Cdh1 upon replication block, thereby stabilizing APC/C substrates, including Cdc7-ASK (Dbf4). Furthermore, motif C of ASK (Dbf4) interacts with the N-terminal region of RAD18 ubiquitin ligase, and this interaction is required for chromatin binding of RAD18. Impaired interaction of ASK (Dbf4...

  10. Haploinsufficiency and the sex chromosomes from yeasts to humans

    Directory of Open Access Journals (Sweden)

    Oliver Stephen G

    2011-02-01

    Full Text Available Abstract Background Haploinsufficient (HI genes are those for which a reduction in copy number in a diploid from two to one results in significantly reduced fitness. Haploinsufficiency is increasingly implicated in human disease, and so predicting this phenotype could provide insights into the genetic mechanisms behind many human diseases, including some cancers. Results In the present work we show that orthologues of Saccharomyces cerevisiae HI genes are preferentially retained across the kingdom Fungi, and that the HI genes of S. cerevisiae can be used to predict haploinsufficiency in humans. Our HI gene predictions confirm known associations between haploinsufficiency and genetic disease, and predict several further disorders in which the phenotype may be relevant. Haploinsufficiency is also clearly relevant to the gene-dosage imbalances inherent in eukaryotic sex-determination systems. In S. cerevisiae, HI genes are over-represented on chromosome III, the chromosome that determines yeast's mating type. This may be a device to select against the loss of one copy of chromosome III from a diploid. We found that orthologues of S. cerevisiae HI genes are also over-represented on the mating-type chromosomes of other yeasts and filamentous fungi. In animals with heterogametic sex determination, accumulation of HI genes on the sex chromosomes would compromise fitness in both sexes, given X chromosome inactivation in females. We found that orthologues of S. cerevisiae HI genes are significantly under-represented on the X chromosomes of mammals and of Caenorhabditis elegans. There is no X inactivation in Drosophila melanogaster (increased expression of X in the male is used instead and, in this species, we found no depletion of orthologues to yeast HI genes on the sex chromosomes. Conclusion A special relationship between HI genes and the sex/mating-type chromosome extends from S. cerevisiae to Homo sapiens, with the microbe being a useful model for

  11. Phosphorylation of the regulatory beta-subunit of protein kinase CK2 by checkpoint kinase Chk1: identification of the in vitro CK2beta phosphorylation site

    DEFF Research Database (Denmark)

    Kristensen, Lars P; Larsen, Martin Røssel; Højrup, Peter;

    2004-01-01

    The regulatory beta-subunit of protein kinase CK2 mediates the formation of the CK2 tetrameric form and it has functions independent of CK2 catalytic subunit through interaction with several intracellular proteins. Recently, we have shown that CK2beta associates with the human checkpoint kinase Chk...... by the modification of Thr213 but it does require the presence of an active Chk1 kinase....

  12. SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature.

    Science.gov (United States)

    Fukami, Maki; Seki, Atsuhito; Ogata, Tsutomu

    2016-04-01

    SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients.

  13. Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism

    Directory of Open Access Journals (Sweden)

    Yan Luo

    2001-01-01

    Full Text Available Checkpoint kinase 1 (Chki is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

  14. MRN- and 9-1-1-Independent Activation of the ATR-Chk1 Pathway during the Induction of the Virulence Program in the Phytopathogen Ustilago maydis.

    Science.gov (United States)

    Tenorio-Gómez, María; de Sena-Tomás, Carmen; Pérez-Martín, Jose

    2015-01-01

    DNA damage response (DDR) leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation.

  15. Proteasome activity is important for replication recovery, CHK1 phosphorylation and prevention of G2 arrest after low-dose formaldehyde

    Energy Technology Data Exchange (ETDEWEB)

    Ortega-Atienza, Sara; Green, Samantha E.; Zhitkovich, Anatoly, E-mail: anatoly_zhitkovich@brown.edu

    2015-07-15

    Formaldehyde (FA) is a human carcinogen with numerous sources of environmental and occupational exposures. This reactive aldehyde is also produced endogenously during metabolism of drugs and other processes. DNA–protein crosslinks (DPCs) are considered to be the main genotoxic lesions for FA. Accumulating evidence suggests that DPC repair in high eukaryotes involves proteolysis of crosslinked proteins. Here, we examined a role of the main cellular proteolytic machinery proteasomes in toxic responses of human lung cells to low FA doses. We found that transient inhibition of proteasome activity increased cytotoxicity and diminished clonogenic viability of FA-treated cells. Proteasome inactivation exacerbated suppressive effects of FA on DNA replication and increased the levels of the genotoxic stress marker γ-H2AX in normal human cells. A transient loss of proteasome activity in FA-exposed cells also caused delayed perturbations of cell cycle, which included G2 arrest and a depletion of S-phase populations at FA doses that had no effects in control cells. Proteasome activity diminished p53-Ser15 phosphorylation but was important for FA-induced CHK1 phosphorylation, which is a biochemical marker of DPC proteolysis in replicating cells. Unlike FA, proteasome inhibition had no effect on cell survival and CHK1 phosphorylation by the non-DPC replication stressor hydroxyurea. Overall, we obtained evidence for the importance of proteasomes in protection of human cells against biologically relevant doses of FA. Biochemically, our findings indicate the involvement of proteasomes in proteolytic repair of DPC, which removes replication blockage by these highly bulky lesions. - Highlights: • Proteasome inhibition enhances cytotoxicity of low-dose FA in human lung cells. • Active proteasomes diminish replication-inhibiting effects of FA. • Proteasome activity prevents delayed G2 arrest in FA-treated cells. • Proteasome inhibition exacerbates replication stress by FA in

  16. MRN- and 9-1-1-Independent Activation of the ATR-Chk1 Pathway during the Induction of the Virulence Program in the Phytopathogen Ustilago maydis.

    Directory of Open Access Journals (Sweden)

    María Tenorio-Gómez

    Full Text Available DNA damage response (DDR leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation.

  17. Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy

    NARCIS (Netherlands)

    Vlaskamp, Danique R.M.; Rump, Patrick; Callenbach, Petra M.C.; Vos, Yvonne J.; Sikkema-Raddatz, Birgit; van Ravenswaaij-Arts, Conny M.A.; Brouwer, Oebele F.

    2016-01-01

    We describe an 18-year-old male patient with myoclonic astatic epilepsy (MAE), moderate to severe intellectual disability, behavioural problems, several dysmorphisms and a 1.2-Mb de novo deletion on chromosome 16p11.2. This deletion results in haploinsufficiency of STX1B and other genes. Recently, v

  18. SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature.

    Science.gov (United States)

    Fukami, Maki; Seki, Atsuhito; Ogata, Tsutomu

    2016-04-01

    SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients. PMID:27194967

  19. SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature

    Science.gov (United States)

    Fukami, Maki; Seki, Atsuhito; Ogata, Tsutomu

    2016-01-01

    SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients. PMID:27194967

  20. Mangrove dolabrane-type of diterpenes tagalsins suppresses tumor growth via ROS-mediated apoptosis and ATM/ATR-Chk1/Chk2-regulated cell cycle arrest.

    Science.gov (United States)

    Neumann, Jennifer; Yang, Yi; Köhler, Rebecca; Giaisi, Marco; Witzens-Harig, Mathias; Liu, Dong; Krammer, Peter H; Lin, Wenhan; Li-Weber, Min

    2015-12-01

    Natural compounds are an important source for drug development. With an increasing cancer rate worldwide there is an urgent quest for new anti-cancer drugs. In this study, we show that a group of dolabrane-type of diterpenes, collectively named tagalsins, isolated from the Chinese mangrove genus Ceriops has potent cytotoxicity on a panel of hematologic cancer cells. Investigation of the molecular mechanisms by which tagalsins kill malignant cells revealed that it induces a ROS-mediated damage of DNA. This event leads to apoptosis induction and blockage of cell cycle progression at S-G2 phase via activation of the ATM/ATR-Chk1/Chk2 check point pathway. We further show that tagalsins suppress growth of human T-cell leukemia xenografts in vivo. Tagalsins show only minor toxicity on healthy cells and are well tolerated by mice. Our study shows a therapeutic potential of tagalsins for the treatment of hematologic malignancies and a new source of anticancer drugs. PMID:26061604

  1. Complex Haploinsufficiency-Based Genetic Analysis of the NDR/Lats Kinase Cbk1 Provides Insight into Its Multiple Functions in Candida albicans.

    Science.gov (United States)

    Saputo, Sarah; Norman, Kaitlyn L; Murante, Thomas; Horton, Brooke N; Diaz, Jacinto De La Cruz; DiDone, Louis; Colquhoun, Jennifer; Schroeder, Jeremy W; Simmons, Lyle A; Kumar, Anuj; Krysan, Damian J

    2016-07-01

    Although the analysis of genetic interactions and networks is a powerful approach to understanding biology, it has not been applied widely to the pathogenic yeast Candida albicans Here, we describe the use of both screening and directed genetic interaction studies based on complex haploinsufficiency to probe the function of the R: egulation of A: ce2 and M: orphogenesis (RAM) pathway in C. albicans A library of 5200 Tn7-mutagenized derivatives of a parental strain heterozygous at CBK1, the key kinase in the RAM pathway, was screened for alterations in serum-induced filamentation. Following confirmation of phenotypes and identification of insertion sites by sequencing, a set of 36 unique double heterozygous strains showing complex haploinsufficiency was obtained. In addition to a large set of genes regulated by the RAM transcription factor Ace2, genes related to cell wall biosynthesis, cell cycle, polarity, oxidative stress, and nitrogen utilization were identified. Follow-up analysis led to the first demonstration that the RAM pathway is required for oxidative stress tolerance in a manner related to the two-component-regulated kinase Chk1 and revealed a potential direct connection between the RAM pathway and the essential Mps1 spindle pole-related kinase. In addition, genetic interactions with CDC42-related genes MSB1, a putative scaffold protein, and RGD3, a putative Rho GTPase-activating protein (GAP) were identified. We also provide evidence that Rgd3 is a GAP for Cdc42 and show that its localization and phosphorylation are dependent on Cbk1. PMID:27206715

  2. Further confirmation of the MED13L haploinsufficiency syndrome

    NARCIS (Netherlands)

    van Haelst, M.M.; Monroe, G.R.; Duran, K.J.; van Binsbergen, E.; Breur, J.M.P.J.; Giltay, J.C.; van Haaften, G.W.

    2015-01-01

    MED13L haploinsufficiency syndrome has been described in two patients and is characterized by moderate intellectual disability (ID), conotruncal heart defects, facial abnormalities and hypotonia. Missense mutations in MED13L are linked to transposition of the great arteries and non-syndromal intelle

  3. Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF-κB-Regulated Anti-Apoptosis and p53/PCNA- and ATM/ATR-Chk1/2-Controlled DNA-Damage Response Pathways.

    Science.gov (United States)

    Zhao, Tuo; Tang, Xin; Umeshappa, Channakeshava Sokke; Ma, Hong; Gao, Haijun; Deng, Yulin; Freywald, Andrew; Xiang, Jim

    2016-09-01

    Microgravity has been known to induce cell death. However, its underlying mechanism is less studied. In this study, BL6-10 melanoma cells were cultured in flasks under simulated microgravity (SMG). We examined cell apoptosis, and assessed expression of genes associated with apoptosis and genes regulating apoptosis in cells under SMG. We demonstrate that SMG induces cell morphological changes and microtubule alterations by confocal microscopy, and enhances apoptosis by flow cytometry, which was associated with up- and down-regulation of pro-apoptotic and anti-apoptotic genes, respectively. Moreover, up- and down-regulation of pro-apoptotic (Caspases 3, 7, 8) and anti-apoptotic (Bcl2 and Bnip3) molecules was confirmed by Western blotting analysis. Western blot analysis also indicates that SMG causes inhibition of an apoptosis suppressor, pNF-κB-p65, which is complemented by the predominant localization of NF-κB-p65 in the cytoplasm. SMG also reduces expression of molecules regulating the NF-κB pathway including Uev1A, TICAM, TRAF2, and TRAF6. Interestingly, 10 DNA repair genes are down-regulated in cells exposed to SMG, among which down-regulation of Parp, Ercc8, Rad23, Rad51, and Ku70 was confirmed by Western blotting analysis. In addition, we demonstrate a significant inhibition of molecules involved in the DNA-damage response, such as p53, PCNA, ATM/ATR, and Chk1/2. Taken together, our work reveals that SMG promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF/NF-κB-regulated apoptosis and the p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways. Thus, our investigation provides novel information, which may help us to determine the cause of negative alterations in human physiology occurring at spaceflight environment. J. Cell. Biochem. 117: 2138-2148, 2016. © 2016 Wiley Periodicals, Inc. PMID:26887372

  4. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects.

    Directory of Open Access Journals (Sweden)

    Weining Lu

    2007-05-01

    Full Text Available Complex central nervous system (CNS malformations frequently coexist with other developmental abnormalities, but whether the associated defects share a common genetic basis is often unclear. We describe five individuals who share phenotypically related CNS malformations and in some cases urinary tract defects, and also haploinsufficiency for the NFIA transcription factor gene due to chromosomal translocation or deletion. Two individuals have balanced translocations that disrupt NFIA. A third individual and two half-siblings in an unrelated family have interstitial microdeletions that include NFIA. All five individuals exhibit similar CNS malformations consisting of a thin, hypoplastic, or absent corpus callosum, and hydrocephalus or ventriculomegaly. The majority of these individuals also exhibit Chiari type I malformation, tethered spinal cord, and urinary tract defects that include vesicoureteral reflux. Other genes are also broken or deleted in all five individuals, and may contribute to the phenotype. However, the only common genetic defect is NFIA haploinsufficiency. In addition, previous analyses of Nfia(-/- knockout mice indicate that Nfia deficiency also results in hydrocephalus and agenesis of the corpus callosum. Further investigation of the mouse Nfia(+/- and Nfia(-/- phenotypes now reveals that, at reduced penetrance, Nfia is also required in a dosage-sensitive manner for ureteral and renal development. Nfia is expressed in the developing ureter and metanephric mesenchyme, and Nfia(+/- and Nfia(-/- mice exhibit abnormalities of the ureteropelvic and ureterovesical junctions, as well as bifid and megaureter. Collectively, the mouse Nfia mutant phenotype and the common features among these five human cases indicate that NFIA haploinsufficiency contributes to a novel human CNS malformation syndrome that can also include ureteral and renal defects.

  5. Sox9-haploinsufficiency causes glucose intolerance in mice.

    Directory of Open Access Journals (Sweden)

    Claire L Dubois

    Full Text Available The HMG box transcription factor Sox9 plays a critical role in progenitor cell expansion during pancreas organogenesis and is required for proper endocrine cell development in the embryo. Based on in vitro studies it has been suggested that Sox9 controls expression of a network of important developmental regulators, including Tcf2/MODY5, Hnf6, and Foxa2, in pancreatic progenitor cells. Here, we sought to: 1 determine whether Sox9 regulates this transcriptional network in vivo and 2 investigate whether reduced Sox9 gene dosage leads to impaired glucose homeostasis in adult mice. Employing two genetic models of temporally-controlled Sox9 inactivation in pancreatic progenitor cells, we demonstrate that contrary to in vitro findings, Sox9 is not required for Tcf2, Hnf6, or Foxa2 expression in vivo. Moreover, our analysis revealed a novel role for Sox9 in maintaining the expression of Pdx1/MODY4, which is an important transcriptional regulator of beta-cell development. We further show that reduced beta-cell mass in Sox9-haploinsufficient mice leads to glucose intolerance during adulthood. Sox9-haploinsufficient mice displayed 50% reduced beta-cell mass at birth, which recovered partially via a compensatory increase in beta-cell proliferation early postnatally. Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. Glucose intolerance in Sox9-haploinsufficient mice suggests that mutations in Sox9 could play a role in diabetes in humans.

  6. Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced cytotoxicity in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Rong-guang SHAO; Chun-Xia CAO; Yves POMMIER

    2004-01-01

    AIM: To investigate whether 7-hydroxystaurosporine (UCN-01) affects cell cycle progression in arabinosylcytosine (ara-C) treated human colon carcinoma HT-29 cells. METHODS: Cytotoxicity, DNA synthesis, cell cycle distribution,protein level, and kinase activity were determined by clonogenic assay, flow cytometry, DNA synthesis assay,immunoblotting, and kinase assays, respectively. RESULTS: UCN-01 abrogated an S/G2-phase checkpoint in HT29 cells treated with ara-C. When UCN-01 was added after treatment with ara-C, the rate of recovery of DNA synthesis was enhanced and colony-forming ability diminished. Thus, premature recovery of DNA synthesis was associated with increased cytotoxicity. Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities, Cdc25C phosphorylation, and Chkl kinase activity were consistent with UCN-01-induced abrogation of the S/G2-phase checkpoint in ara-C treated cells. CONCLUSION: The abrogation of the S/G2 checkpoint may be due to inhibition of Chkl kinase by UCN-01. The enhanced cytotoxicity produced when UCN-01 was combined with ara-C suggested a rationale for the use of this drug combination for tumors that might be susceptible to cell cycle checkpoint abrogation.

  7. Haploinsufficiency for Steroidogenic Factor 1 Affects Maternal Behavior in Mice

    Science.gov (United States)

    Spanic, Tanja; Grgurevic, Neza; Majdic, Gregor

    2016-01-01

    Steroidogenic factor 1 (SF-1), officially designated NR5A1, is essential for gonadal and adrenal development and for the normal structure of the ventromedial hypothalamus (VMH), as demonstrated by SF-1 knockout mice (SF-1 KO), but much less is known about the possible effects of haploinsufficiency of the SF-1 gene. In the present study, maternal behavior in SF-1 KO heterozygous mice was evaluated. Behavioral tests revealed that SF-1 KO heterozygous females have impaired maternal behavior. In comparison to wild-type (WT) females, SF-1 KO heterozygous females retrieved significantly fewer pups into their nests, latency to retrieve and crouch over the pups was longer, and their nests were lower quality. As suggested by previous studies full dosage of SF-1 gene is needed for appropriate stress response and expression of brain-derived neurotrophic factor (BDNF) in the brain, and this might present a mechanism through which maternal behavior in SF-1 KO heterozygous females is impaired. PMID:27445727

  8. Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice.

    Science.gov (United States)

    Unnikrishnan, Archana; Raffoul, Julian J; Patel, Hiral V; Prychitko, Thomas M; Anyangwe, Njwen; Meira, Lisiane B; Friedberg, Errol C; Cabelof, Diane C; Heydari, Ahmad R

    2009-06-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-kappaB, and the major 5'-endonuclease in base excision repair (BER). We utilized mice containing a heterozygous gene-targeted deletion of APE1/Ref-1 (Apex(+/-)) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency results in a significant decline in NF-kappaB DNA-binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress, in which significant increases in GADD45g expression, p53 protein stability, and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UNG) and bifunctional (OGG1) DNA glycosylase-initiated BER in the liver of Apex(+/-) mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), whereas removal of uracil is increased in liver nuclear extracts of mice using an in vitro BER assay. Apex(+/-) mice exposed to 2-NP displayed a significant decline in 3'-OH-containing single-strand breaks and an increase in aldehydic lesions in their liver DNA, suggesting an accumulation of repair intermediates of failed bifunctional DNA glycosylase-initiated BER. PMID:19268524

  9. Hyperactive RAS/PI3-K/MAPK Signaling Cascade in Migration and Adhesion of Nf1 Haploinsufficient Mesenchymal Stem/Progenitor Cells

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    Yuan Zhou

    2015-06-01

    Full Text Available Neurofibromatosis type 1 (NF1 is an autosomal dominant disease caused by mutations in the NF1 tumor suppressor gene, which affect approximately 1 out of 3000 individuals. Patients with NF1 suffer from a range of malignant and nonmalignant manifestations such as plexiform neurofibromas and skeletal abnormalities. We previously demonstrated that Nf1 haploinsufficiency in mesenchymal stem/progenitor cells (MSPCs results in impaired osteoblastic differentiation, which may be associated with the skeletal manifestations in NF1 patients. Here we sought to further ascertain the role of Nf1 in modulating the migration and adhesion of MSPCs of the Nf1 haploinsufficient (Nf1+/− mice. Nf1+/− MSPCs demonstrated increased nuclear-cytoplasmic ratio, increased migration, and increased actin polymerization as compared to wild-type (WT MSPCs. Additionally, Nf1+/− MSPCs were noted to have significantly enhanced cell adhesion to fibronectin with selective affinity for CH271 with an overexpression of its complimentary receptor, CD49e. Nf1+/− MSPCs also showed hyperactivation of phosphoinositide 3-kinase (PI3-K and mitogen activated protein kinase (MAPK signaling pathways when compared to WT MSPCs, which were both significantly reduced in the presence of their pharmacologic inhibitors, LY294002 and PD0325901, respectively. Collectively, our study suggests that both PI3-K and MAPK signaling pathways play a significant role in enhanced migration and adhesion of Nf1 haploinsufficient MSPCs.

  10. Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

    Science.gov (United States)

    Ateca-Cabarga, Juan C.; Cosa, Alejandro; Pallarés, Vicente; López-Atalaya, José P.; Barco, Ángel; Canals, Santiago; Moratal, David

    2015-11-01

    The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p brain tissues in a region by region basis between cbp+/- and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

  11. Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer

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    Sanaz Manteghi

    2016-05-01

    Full Text Available Endosomal sorting complexes required for transport (ESCRT drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gene cluster 3p21.3 drives tumorigenesis in vivo. Indeed, Ptpn23+/− loss predisposes mice to sporadic lung adenoma, B cell lymphoma, and promotes Myc-driven lymphoma onset, dissemination, and aggressiveness. Ptpn23+/−-derived tumors exhibit an unaltered remaining allele and maintain 50% of HD-PTP expression. Consistent with the role of HD-PTP in attenuation of integrin recycling, cell migration, and invasion, hemizygous Ptpn23+/− loss increases integrin β1-dependent B cell lymphoma survival and dissemination. Finally, we reveal frequent PTPN23 deletion and downregulation in human tumors that correlates with poor survival. Altogether, we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking.

  12. Adenylyl cyclase 3 haploinsufficiency confers susceptibility to diet-induced obesity and insulin resistance in mice

    Science.gov (United States)

    Tong, Tao; Shen, Ying; Lee, Han-Woong; Yu, Rina; Park, Taesun

    2016-01-01

    Adenylyl cyclase 3 (Adcy3), a member of the mammalian adenylyl cyclase family responsible for generating the second messenger cAMP, has long been known to play an essential role in olfactory signal transduction. Here, we demonstrated that Adcy3 heterozygous null mice displayed increased visceral adiposity in the absence of hyperphagia and developed abnormal metabolic features characterized by impaired insulin sensitivity, dyslipidemia, and increased plasma levels of proinflammatory cytokines on both chow and high-fat diet (HFD). Of note, HFD decreased the Adcy3 expression in white adipose tissue, liver, and muscle. We also report for the first time that Adcy3 haploinsufficiency resulted in reduced expression of genes involved in thermogenesis, fatty acid oxidation, and insulin signaling, with enhanced expression of genes related to adipogenesis in peripheral tissues of mice. In conclusion, these findings suggest that cAMP signals generated by Adcy3 in peripheral tissues may play a pivotal role in modulating obesity and insulin sensitivity. PMID:27678003

  13. Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

    Science.gov (United States)

    Ateca-Cabarga, Juan C.; Cosa, Alejandro; Pallarés, Vicente; López-Atalaya, José P.; Barco, Ángel; Canals, Santiago; Moratal, David

    2015-11-01

    The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp+/- and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

  14. High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene

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    Jehnan Liu

    2015-03-01

    Conclusion: High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis.

  15. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication

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    Bozdagi Ozlem

    2010-12-01

    Full Text Available Abstract Background SHANK3 is a protein in the core of the postsynaptic density (PSD and has a critical role in recruiting many key functional elements to the PSD and to the synapse, including components of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA, metabotropic glutamate (mGlu and N-methyl-D-aspartic acid (NMDA glutamate receptors, as well as cytoskeletal elements. Loss of a functional copy of the SHANK3 gene leads to the neurobehavioral manifestations of 22q13 deletion syndrome and/or to autism spectrum disorders. The goal of this study was to examine the effects of haploinsufficiency of full-length Shank3 in mice, focusing on synaptic development, transmission and plasticity, as well as on social behaviors, as a model for understanding SHANK3 haploinsufficiency in humans. Methods We used mice with a targeted disruption of Shank3 in which exons coding for the ankyrin repeat domain were deleted and expression of full-length Shank3 was disrupted. We studied synaptic transmission and plasticity by multiple methods, including patch-clamp whole cell recording, two-photon time-lapse imaging and extracellular recordings of field excitatory postsynaptic potentials. We also studied the density of GluR1-immunoreactive puncta in the CA1 stratum radiatum and carried out assessments of social behaviors. Results In Shank3 heterozygous mice, there was reduced amplitude of miniature excitatory postsynaptic currents from hippocampal CA1 pyramidal neurons and the input-output (I/O relationship at Schaffer collateral-CA1 synapses in acute hippocampal slices was significantly depressed; both of these findings indicate a reduction in basal neurotransmission. Studies with specific inhibitors demonstrated that the decrease in basal transmission reflected reduced AMPA receptor-mediated transmission. This was further supported by the observation of reduced numbers of GluR1-immunoreactive puncta in the stratum radiatum. Long-term potentiation (LTP

  16. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

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    Janice B B Lam

    Full Text Available BACKGROUND: Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1. CONCLUSION: Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K

  17. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes.

    Science.gov (United States)

    Visconte, Valeria; Rogers, Heesun J; Singh, Jarnail; Barnard, John; Bupathi, Manoj; Traina, Fabiola; McMahon, James; Makishima, Hideki; Szpurka, Hadrian; Jankowska, Anna; Jerez, Andres; Sekeres, Mikkael A; Saunthararajah, Yogen; Advani, Anjali S; Copelan, Edward; Koseki, Haruhiko; Isono, Kyoichi; Padgett, Richard A; Osman, Sami; Koide, Kazunori; O'Keefe, Christine; Maciejewski, Jaroslaw P; Tiu, Ramon V

    2012-10-18

    Whole exome/genome sequencing has been fundamental in the identification of somatic mutations in the spliceosome machinery in myelodysplastic syndromes (MDSs) and other hematologic disorders. SF3B1, splicing factor 3b subunit 1 is mutated in 60%-80% of refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T), 2 distinct subtypes of MDS and MDS/myeloproliferative neoplasms (MDSs/MPNs). An idiosyncratic feature of RARS/RARS-T is the presence of abnormal sideroblasts characterized by iron overload in the mitochondria, called RS. Based on the high frequency of mutations of SF3B1 in RARS/RARS-T, we investigated the consequences of SF3B1 alterations. Ultrastructurally, SF3B1 mutants showed altered iron distribution characterized by coarse iron deposits compared with wild-type RARS patients by transmission electron microscopy. SF3B1 knockdown experiments in K562 cells resulted in down-regulation of U2-type intron-splicing by RT-PCR. RNA-sequencing analysis of SF3B1 mutants showed differentially used genes relevant in MDS pathogenesis, such as ASXL1, CBL, EZH, and RUNX families. A SF3B pharmacologic inhibitor, meayamycin, induced the formation of RS in healthy BM cells. Further, BM aspirates of Sf3b1 heterozygous knockout mice showed RS by Prussian blue. In conclusion, we report the first experimental evidence of the association between SF3B1 and RS phenotype. Our data suggest that SF3B1 haploinsufficiency leads to RS formation.

  18. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A.

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    Glòria Arqué

    Full Text Available BACKGROUND: Pathogenic aneuploidies involve the concept of dosage-sensitive genes leading to over- and underexpression phenotypes. Monosomy 21 in human leads to mental retardation and skeletal, immune and respiratory function disturbances. Most of the human condition corresponds to partial monosomies suggesting that critical haploinsufficient genes may be responsible for the phenotypes. The DYRK1A gene is localized on the human chromosome 21q22.2 region, and has been proposed to participate in monosomy 21 phenotypes. It encodes a dual-specificity kinase involved in neuronal development and in adult brain physiology, but its possible role as critical haploinsufficient gene in cognitive function has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: We used mice heterozygous for a Dyrk1A targeted mutation (Dyrk1A+/- to investigate the implication of this gene in the cognitive phenotypes of monosomy 21. Performance of Dyrk1A+/- mice was assayed 1/ in a navigational task using the standard hippocampally related version of the Morris water maze, 2/ in a swimming test designed to reveal potential kinesthetic and stress-related behavioral differences between control and heterozygous mice under two levels of aversiveness (25 degrees C and 17 degrees C and 3/ in a long-term novel object recognition task, sensitive to hippocampal damage. Dyrk1A+/- mice showed impairment in the development of spatial learning strategies in a hippocampally-dependent memory task, they were impaired in their novel object recognition ability and were more sensitive to aversive conditions in the swimming test than euploid control animals. CONCLUSIONS/SIGNIFICANCE: The present results are clear examples where removal of a single gene has a profound effect on phenotype and indicate that haploinsufficiency of DYRK1A might contribute to an impairment of cognitive functions and stress coping behavior in human monosomy 21.

  19. The haploinsufficiency profile of α-hederin suggests a caspofungin-like antifungal mode of action.

    Science.gov (United States)

    Prescott, Thomas A K; Rigby, Luke P; Veitch, Nigel C; Simmonds, Monique S J

    2014-05-01

    The leaves of common ivy (Hedera helix) contain the cytotoxic saponin α-hederin, which is inhibitory to Candida albicans at low concentrations. To investigate the mode of action of α-hederin, a haploinsufficiency screen was carried out using a library of 1152 Saccharomyces cerevisiae deletion strains. An ethanol ivy extract containing α-hederin was used in the initial screen to reduce the amount of compound required. Strains exhibiting disproportionately low growth were then examined in more detail by comparing growth curves in the presence and absence of α-hederin. This approach identified three hypersensitive strains carrying gene deletions for components of the transcription related proteins SWI/SNF, RNA polymerase II and the RSC complex. Saponin cytotoxicity is often attributed to membrane damage, however α-hederin did not induce hypersensitivity with an aminophospholipid translocase deletion strain that is frequently hypersensitive to membrane damaging agents. The haploinsufficiency profile of α-hederin is most similar to that reported for drugs such as caspofungin that inhibit synthesis of the fungal cell wall. Screening with plant extracts rather than isolated compounds, provides a valuable shortcut in haploinsufficiency screening provided hypersensitive strains are then confirmed as such using purified active principles. PMID:24569176

  20. Telomere Elongation and Naive Pluripotent Stem Cells Achieved from Telomerase Haplo-Insufficient Cells by Somatic Cell Nuclear Transfer

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    Li-Ying Sung

    2014-12-01

    Full Text Available Haplo-insufficiency of telomerase genes in humans leads to telomere syndromes such as dyskeratosis congenital and idiopathic pulmonary fibrosis. Generation of pluripotent stem cells from telomerase haplo-insufficient donor cells would provide unique opportunities toward the realization of patient-specific stem cell therapies. Recently, pluripotent human embryonic stem cells (ntESCs have been efficiently achieved by somatic cell nuclear transfer (SCNT. We tested the hypothesis that SCNT could effectively elongate shortening telomeres of telomerase haplo-insufficient cells in the ntESCs with relevant mouse models. Indeed, telomeres of telomerase haplo-insufficient (Terc+/− mouse cells are elongated in ntESCs. Moreover, ntESCs derived from Terc+/− cells exhibit naive pluripotency as evidenced by generation of Terc+/− ntESC clone pups by tetraploid embryo complementation, the most stringent test of naive pluripotency. These data suggest that SCNT could offer a powerful tool to reprogram telomeres and to discover the factors for robust restoration of telomeres and pluripotency of telomerase haplo-insufficient somatic cells.

  1. Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency.

    Science.gov (United States)

    Ikeda, Kenichiro; Ueda, Takeshi; Yamasaki, Norimasa; Nakata, Yuichiro; Sera, Yasuyuki; Nagamachi, Akiko; Miyama, Takahiko; Kobayashi, Hiroshi; Takubo, Keiyo; Kanai, Akinori; Oda, Hideaki; Wolff, Linda; Honda, Zen-Ichiro; Ichinohe, Tatsuo; Matsubara, Akio; Suda, Toshio; Inaba, Toshiya; Honda, Hiroaki

    2016-01-01

    Polycomb repressive complex 2 (PRC2) participates in transcriptional repression through methylation of histone H3K27. The WD-repeat protein embryonic ectoderm development (EED) is a non-catalytic but an essential component of PRC2 and its mutations were identified in hematopoietic malignancies. To clarify the role(s) of EED in adult hematopoiesis and leukemogenesis, we generated Eed conditional knockout (Eed(Δ/Δ)) mice. Eed(Δ/Δ) mice died in a short period with rapid decrease of hematopoietic cells. Hematopoietic stem/progenitor cells (HSPCs) were markedly decreased with impaired bone marrow (BM) repopulation ability. Cell cycle analysis of HSPCs demonstrated increased S-phase fraction coupled with suppressed G0/G1 entry. Genes encoding cell adhesion molecules are significantly enriched in Eed(Δ/Δ) HSPCs, and consistently, Eed(Δ/Δ) HSPCs exhibited increased attachment to a major extracellular matrix component, fibronectin. Thus, EED deficiency increases proliferation on one side but promotes quiescence possibly by enhanced adhesion to the hematopoietic niche on the other, and these conflicting events would lead to abnormal differentiation and functional defect of Eed(Δ/Δ) HSPCs. In addition, Eed haploinsufficiency induced hematopoietic dysplasia, and Eed heterozygous mice were susceptible to malignant transformation and developed leukemia in cooperation with Evi1 overexpression. Our results demonstrated differentiation stage-specific and dose-dependent roles of EED in normal hematopoiesis and leukemogenesis. PMID:27432459

  2. Haploinsufficiency of activation-induced deaminase for antibody diversification and chromosome translocations both in vitro and in vivo.

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    Isora V Sernández

    Full Text Available The humoral immune response critically relies on the secondary diversification of antibodies. This diversification takes places through somatic remodelling of the antibody genes by two molecular mechanisms, Class Switch Recombination (CSR and Somatic Hypermutation (SHM. The enzyme Activation Induced Cytidine Deaminase (AID initiates both SHM and CSR by deaminating cytosine residues on the DNA of immunoglobulin genes. While crucial for immunity, AID-catalysed deamination is also the triggering event for the generation of lymphomagenic chromosome translocations. To address whether restricting the levels of AID expression in vivo contributes to the regulation of its function, we analysed mice harbouring a single copy of the AID gene (AID(+/-. AID(+/- mice express roughly 50% of normal AID levels, and display a mild hyperplasia, reminiscent of AID deficient mice and humans. Moreover, we found that AID(+/- cells have an impaired competence for CSR and SHM, which indicates that AID gene dose is limiting for its physiologic function. We next evaluated the impact of AID reduction in AID(+/- mice on the generation of chromosome translocations. Our results show that the frequency of AID-promoted c-myc/IgH translocations is reduced in AID(+/- mice, both in vivo and in vitro. Therefore, AID is haploinsufficient for antibody diversification and chromosome translocations. These findings suggest that limiting the physiologic levels of AID expression can be a regulatory mechanism that ensures an optimal balance between immune proficiency and genome integrity.

  3. Maintenance of the functional integrity of mouse hematopoiesis by EED and promotion of leukemogenesis by EED haploinsufficiency

    Science.gov (United States)

    Ikeda, Kenichiro; Ueda, Takeshi; Yamasaki, Norimasa; Nakata, Yuichiro; Sera, Yasuyuki; Nagamachi, Akiko; Miyama, Takahiko; Kobayashi, Hiroshi; Takubo, Keiyo; Kanai, Akinori; Oda, Hideaki; Wolff, Linda; Honda, Zen-ichiro; Ichinohe, Tatsuo; Matsubara, Akio; Suda, Toshio; Inaba, Toshiya; Honda, Hiroaki

    2016-01-01

    Polycomb repressive complex 2 (PRC2) participates in transcriptional repression through methylation of histone H3K27. The WD-repeat protein embryonic ectoderm development (EED) is a non-catalytic but an essential component of PRC2 and its mutations were identified in hematopoietic malignancies. To clarify the role(s) of EED in adult hematopoiesis and leukemogenesis, we generated Eed conditional knockout (EedΔ/Δ) mice. EedΔ/Δ mice died in a short period with rapid decrease of hematopoietic cells. Hematopoietic stem/progenitor cells (HSPCs) were markedly decreased with impaired bone marrow (BM) repopulation ability. Cell cycle analysis of HSPCs demonstrated increased S-phase fraction coupled with suppressed G0/G1 entry. Genes encoding cell adhesion molecules are significantly enriched in EedΔ/Δ HSPCs, and consistently, EedΔ/Δ HSPCs exhibited increased attachment to a major extracellular matrix component, fibronectin. Thus, EED deficiency increases proliferation on one side but promotes quiescence possibly by enhanced adhesion to the hematopoietic niche on the other, and these conflicting events would lead to abnormal differentiation and functional defect of EedΔ/Δ HSPCs. In addition, Eed haploinsufficiency induced hematopoietic dysplasia, and Eed heterozygous mice were susceptible to malignant transformation and developed leukemia in cooperation with Evi1 overexpression. Our results demonstrated differentiation stage-specific and dose-dependent roles of EED in normal hematopoiesis and leukemogenesis. PMID:27432459

  4. Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan

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    Chen, Phang-Lang; Chen, Chi-Fen; Chen, Yumay; Guo, Xuning Emily; Huang, Chun-Kai; Shew, Jin-Yuh; Reddick, Robert L.; Wallace, Douglas C.; Lee, Wen-Hwa

    2012-01-01

    Mitochondrial dysfunction has been a hallmark of cancer. However, whether it plays a causive role awaits to be elucidated. Here, using an animal model derived from inactivation of SUV3, a mitochondrial helicase, we demonstrated that mSuv3+/− mice harbored increased mtDNA mutations and decreased mtDNA copy numbers, leading to tumor development in various sites and shortened lifespan. These phenotypes were transmitted maternally, indicating the etiological role of the mitochondria. Importantly,...

  5. BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription.

    Science.gov (United States)

    Dias, Cristina; Estruch, Sara B; Graham, Sarah A; McRae, Jeremy; Sawiak, Stephen J; Hurst, Jane A; Joss, Shelagh K; Holder, Susan E; Morton, Jenny E V; Turner, Claire; Thevenon, Julien; Mellul, Kelly; Sánchez-Andrade, Gabriela; Ibarra-Soria, Ximena; Deriziotis, Pelagia; Santos, Rui F; Lee, Song-Choon; Faivre, Laurence; Kleefstra, Tjitske; Liu, Pentao; Hurles, Mathew E; Fisher, Simon E; Logan, Darren W

    2016-08-01

    Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes. PMID:27453576

  6. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.

    Science.gov (United States)

    Mao, Hanqian; McMahon, John J; Tsai, Yi-Hsuan; Wang, Zefeng; Silver, Debra L

    2016-09-01

    The exon junction complex (EJC) is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease. PMID:27618312

  7. the Adaptive Response, Genetic Haplo-Insufficiency and Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Geard, Charles R.

    2014-12-12

    The linear no-threshold (LNT) hypothesis is the driving force in the establishment of radiation protection standards. However, the scientific basis for linearity has been brought into question, particularly due to the concerns about induced radiation resistance as it pertains to oxidative stress. Specifically, we investigated the observation that tumor hypoxia is associated with malignant progression, increased metastases, chemo- and radioresistance and poor prognosis. Experiments were conducted with non-malignant 3T3/NIH cells and normal human lung fibroblasts (NHLF) that were subjected to γ-irradiation under the levels of oxygen resembling those in growing tumors, and related our data to the concentrations of dissolved oxygen (DO), which is a better indicator of the amounts of residual oxygen inside the cells cultured in the hypoxic or anoxic atmosphere. We found that at DO levels about 0.5 mg/L cells subjected to both short-term (17 hours) and prolonged (48-72 hours) hypoxia continued to proliferate, and that apoptotic events were decreased at the early hours of hypoxic treatment. We showed that the short-term hypoxia up-regulated p53-binding protein 1 (53BP1) and resulted in facilitated 53BP1 nuclear foci formation and disappearance, thus indicating the higher efficiency of DNA double strand breaks repair processes. The latter was confirmed by the lower micronuclei incidence in irradiated hypoxic cells.

  8. SERCA2 Haploinsufficiency in a Mouse Model of Darier Disease Causes a Selective Predisposition to Heart Failure.

    Science.gov (United States)

    Prasad, Vikram; Lorenz, John N; Lasko, Valerie M; Nieman, Michelle L; Huang, Wei; Wang, Yigang; Wieczorek, David W; Shull, Gary E

    2015-01-01

    Null mutations in one copy of ATP2A2, the gene encoding sarco/endoplasmic reticulum Ca(2+)-ATPase isoform 2 (SERCA2), cause Darier disease in humans, a skin condition involving keratinocytes. Cardiac function appears to be unimpaired in Darier disease patients, with no evidence that SERCA2 haploinsufficiency itself causes heart disease. However, SERCA2 deficiency is widely considered a contributing factor in heart failure. We therefore analyzed Atp2a2 heterozygous mice to determine whether SERCA2 haploinsufficiency can exacerbate specific heart disease conditions. Despite reduced SERCA2a levels in heart, Atp2a2 heterozygous mice resembled humans in exhibiting normal cardiac physiology. When subjected to hypothyroidism or crossed with a transgenic model of reduced myofibrillar Ca(2+)-sensitivity, SERCA2 deficiency caused no enhancement of the disease state. However, when combined with a transgenic model of increased myofibrillar Ca(2+)-sensitivity, SERCA2 haploinsufficiency caused rapid onset of hypertrophy, decompensation, and death. These effects were associated with reduced expression of the antiapoptotic Hax1, increased levels of the proapoptotic genes Chop and Casp12, and evidence of perturbations in energy metabolism. These data reveal myofibrillar Ca(2+)-sensitivity to be an important determinant of the cardiac effects of SERCA2 haploinsufficiency and raise the possibility that Darier disease patients are more susceptible to heart failure under certain conditions.

  9. Hypomethylation of ERVs in the sperm of mice haploinsufficient for the histone methyltransferase Setdb1 correlates with a paternal effect on phenotype.

    Science.gov (United States)

    Daxinger, Lucia; Oey, Harald; Isbel, Luke; Whitelaw, Nadia C; Youngson, Neil A; Spurling, Alex; Vonk, Kelly K D; Whitelaw, Emma

    2016-01-01

    The number of reports of paternal epigenetic influences on the phenotype of offspring in rodents is increasing but the molecular events involved remain unclear. Here, we show that haploinsufficiency for the histone 3 lysine 9 methyltransferase Setdb1 in the sire can influence the coat colour phenotype of wild type offspring. This effect occurs when the allele that directly drives coat colour is inherited from the dam, inferring that the effect involves an "in trans" step. The implication of this finding is that epigenetic state of the sperm can alter the expression of genes inherited on the maternally derived chromosomes. Whole genome bisulphite sequencing revealed that Setdb1 mutant mice show DNA hypomethylation at specific classes of transposable elements in the sperm. Our results identify Setdb1 as a paternal effect gene in the mouse and suggest that epigenetic inheritance may be more likely in individuals with altered levels of epigenetic modifiers. PMID:27112447

  10. Dll1 haploinsufficiency in adult mice leads to a complex phenotype affecting metabolic and immunological processes.

    Directory of Open Access Journals (Sweden)

    Isabel Rubio-Aliaga

    Full Text Available BACKGROUND: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1 is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y. Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized. CONCLUSIONS/SIGNIFICANCE: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.

  11. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.

    Science.gov (United States)

    Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

    2015-11-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

  12. Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B

    DEFF Research Database (Denmark)

    Hansen, Christina Halgren; Kjaergaard, S; Bak, M;

    2011-01-01

    Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function...... of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set...... with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general...

  13. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia.

    Science.gov (United States)

    Freischmidt, Axel; Wieland, Thomas; Richter, Benjamin; Ruf, Wolfgang; Schaeffer, Veronique; Müller, Kathrin; Marroquin, Nicolai; Nordin, Frida; Hübers, Annemarie; Weydt, Patrick; Pinto, Susana; Press, Rayomond; Millecamps, Stéphanie; Molko, Nicolas; Bernard, Emilien; Desnuelle, Claude; Soriani, Marie-Hélène; Dorst, Johannes; Graf, Elisabeth; Nordström, Ulrika; Feiler, Marisa S; Putz, Stefan; Boeckers, Tobias M; Meyer, Thomas; Winkler, Andrea S; Winkelman, Juliane; de Carvalho, Mamede; Thal, Dietmar R; Otto, Markus; Brännström, Thomas; Volk, Alexander E; Kursula, Petri; Danzer, Karin M; Lichtner, Peter; Dikic, Ivan; Meitinger, Thomas; Ludolph, Albert C; Strom, Tim M; Andersen, Peter M; Weishaupt, Jochen H

    2015-05-01

    Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.

  14. Haploinsufficiency of cytosolic serine hydroxymethyltransferase in the Smith-Magenis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Elsea, S.H.; Juyal, R.C.; Jiralerspong, S. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-12-01

    Folate-dependent one-carbon metabolism is critical for the synthesis of numerous cellular constituents required for cell growth, and serine hydroxymethyltransferase (SHMT) is central to this process. Our studies reveal that the gene for cytosolic SHMT (cSHMT) maps to the critical interval for Smith-Magenis syndrome (SMS) on chromosome 17p11.2. The basic organization of the cSHMT locus on chromosome 17 was determined and was found to span{approximately}40 kb. The gene for cSHMT was found to be deleted in all 26 SMS patients examined by PCR, FISH, and/or Southern analysis. Furthermore, with respect to haploinsufficiency, cSHMT enzyme activity in patient lymphoblasts was determined to be {approximately}50% that of unaffected parent lymphoblasts. Serine, glycine, and folate levels were also assessed in three SMS patients and were found to be within normal ranges. The possible effects of cSHMT hemizygosity on the SMS phenotype are discussed. 40 refs., 3 figs., 21 tabs.

  15. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

    Directory of Open Access Journals (Sweden)

    Sara N. Koenig

    2015-03-01

    Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  16. Nedd4-2 haploinsufficiency causes hyperactivity and increased sensitivity to inflammatory stimuli

    Science.gov (United States)

    Yanpallewar, Sudhirkumar; Wang, Ting; Koh, Dawn C. I.; Quarta, Eros; Fulgenzi, Gianluca; Tessarollo, Lino

    2016-09-01

    Nedd4-2 (NEDD4L in humans) is a ubiquitin protein ligase best known for its role in regulating ion channel internalization and turnover. Nedd4-2 deletion in mice causes perinatal lethality associated with increased epithelial sodium channel (ENaC) expression in lung and kidney. Abundant data suggest that Nedd4-2 plays a role in neuronal functions and may be linked to epilepsy and dyslexia in humans. We used a mouse model of Nedd4-2 haploinsufficiency to investigate whether an alteration in Nedd4-2 levels of expression affects general nervous system functions. We found that Nedd4-2 heterozygous mice are hyperactive, have increased basal synaptic transmission and have enhanced sensitivity to inflammatory pain. Thus, Nedd4-2 heterozygous mice provide a new genetic model to study inflammatory pain. These data also suggest that in human, SNPs affecting NEDD4L levels may be involved in the development of neuropsychological deficits and peripheral neuropathies and may help unveil the genetic basis of comorbidities.

  17. Effect of systemic heparan sulfate haploinsufficiency on steady state hematopoiesis and engraftment of hematopoietic stem cells.

    Science.gov (United States)

    Shekels, Laurie L; Buelt-Gebhardt, Melissa; Gupta, Pankaj

    2015-06-01

    Heparan sulfate (HS) proteoglycans on stromal and hematopoietic stem/progenitor cells (HSPC) help form the stem cell niche, co-localize molecules that direct stem cell fate, and modulate HSPC homing and retention. Inhibition of HS function mobilizes marrow HSPC. In vitro, HSPC maintenance is influenced by stromal HS structure and concentration. Because inhibition of HS activity or synthesis may be developed for HSPC transplantation, it is important to examine if systemic HS deficiency influences hematopoiesis in vivo. In a transgenic mouse model of HS haploinsufficiency, we examined endogenous hematopoiesis and engraftment of allogeneic bone marrow. Endogenous hematopoiesis was normal except gender-specific alterations in peripheral blood monocyte and platelet counts. Donor engraftment was achieved in all mice following myeloablative irradiation, but HS deficiency in the stromal microenvironment, on HSPC, or both (the 3 test conditions), was associated with a trend towards lower donor engraftment percentage in the bone marrow. Following non-myeloablative irradiation, competitive engraftment was achieved in 22% of mice in the test conditions, vs 50% of control animals (P = 0.03). HS deficiency did not re-direct donor engraftment from bone marrow to spleen or liver. Normal HS levels in the stromal microenvironment and HSPC are required for HSPC engraftment following non-myeloablative conditioning. PMID:25976459

  18. Oxidative stress alters base excision repair pathway and increases apoptotic response in Apurinic/apyrimidinic endonuclease 1/Redox factor-1 haploinsufficient mice

    OpenAIRE

    Unnikrishnan, Archana; Raffoul, Julian J.; Patel, Hiral V.; Prychitko, Thomas M.; Anyangwe, Njwen; Meira, Lisiane B.; Friedberg, Errol C.; Cabelof, Diane C.; Heydari, Ahmad R.

    2009-01-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-κB, and the major 5’-endonuclease in base excision repair (BER). We utilized mice containing heterozygous gene-targeted deletion of APE1/Ref-1 (Apex+/-) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency re...

  19. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency.

    Science.gov (United States)

    Linhares, Natália Duarte; Freire, Maíra Cristina Menezes; Cardenas, Raony Guimarães Corrêa do Carmo Lisboa; Pena, Heloisa Barbosa; Lachlan, Katherine; Dallapiccola, Bruno; Bacino, Carlos; Delobel, Bruno; James, Paul; Thuresson, Ann-Charlotte; Annerén, Göran; Pena, Sérgio D J

    2016-01-01

    Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients.

  20. The haploinsufficient hematopoietic microenvironment is critical to the pathological fracture repair in murine models of neurofibromatosis type 1.

    Directory of Open Access Journals (Sweden)

    Xiaohua Wu

    Full Text Available Germline mutations in the NF1 tumor suppressor gene cause neurofibromatosis type 1 (NF1, a complex genetic disorder with a high predisposition of numerous skeletal dysplasias including short stature, osteoporosis, kyphoscoliosis, and fracture non-union (pseudoarthrosis. We have developed murine models that phenocopy many of the skeletal dysplasias observed in NF1 patients, including reduced bone mass and fracture non-union. We also show that the development of these skeletal manifestations requires an Nf1 haploinsufficient background in addition to nullizygous loss of Nf1 in mesenchymal stem/progenitor cells (MSCs and/or their progenies. This is replicated in two animal models of NF1, PeriCre(+;Nf1(flox/- and Col2.3Cre(+;Nf1(flox/- mice. Adoptive transfer experiments demonstrate a critical role of the Nf1+/- marrow microenvironment in the impaired fracture healing in both models and adoptive transfer of WT bone marrow cells improves fracture healing in these mice. To our knowledge, this is the first demonstration of a non-cell autonomous mechanism in non-malignant NF1 manifestations. Collectively, these data provide evidence of a combinatory effect between nullizygous loss of Nf1 in osteoblast progenitors and haploinsufficiency in hematopoietic cells in the development of non-malignant NF1 manifestations.

  1. Haploinsufficiency of RPS14 in 5q− syndrome is associated with deregulation of ribosomal- and translation-related genes

    Science.gov (United States)

    Pellagatti, Andrea; Hellström-Lindberg, Eva; Giagounidis, Aristoteles; Perry, Janet; Malcovati, Luca; Della Porta, Matteo G; Jädersten, Martin; Killick, Sally; Fidler, Carrie; Cazzola, Mario; Wainscoat, James S; Boultwood, Jacqueline

    2008-01-01

    We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14, which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q− syndrome. Patients with Diamond-Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal- and translation-related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal- and translation-related genes in the CD34+ cells of 15 myelodysplastic syndrome (MDS) patients with 5q− syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls. In this three-way comparison, 55 of 579 ribosomal- and translation-related probe sets were found to be significantly differentially expressed, with approximately 90% of these showing lower expression levels in the 5q− syndrome patient group. Using hierarchical clustering, patients with the 5q− syndrome could be separated both from other patients with RA and healthy controls solely on the basis of the deregulated expression of ribosomal- and translation-related genes. Patients with the 5q− syndrome have a defect in the expression of genes involved in ribosome biogenesis and in the control of translation, suggesting that the 5q− syndrome represents a disorder of aberrant ribosome biogenesis. PMID:18477045

  2. Haploinsufficiency after successive loss of signaling reveals a role for ERECTA-family genes in Arabidopsis ovule development.

    Science.gov (United States)

    Pillitteri, Lynn Jo; Bemis, Shannon M; Shpak, Elena D; Torii, Keiko U

    2007-09-01

    The Arabidopsis genome contains three ERECTA-family genes, ERECTA (ER), ERECTA-LIKE 1 (ERL1) and ERL2 that encode leucine-rich repeat receptor-like kinases. This gene family acts synergistically to coordinate cell proliferation and growth during above-ground organogenesis with the major player, ER, masking the loss-of-function phenotypes of the other two members. To uncover the specific developmental consequence and minimum threshold requirement for signaling, ER-family gene function was successively eliminated. We report here that ERL2 is haploinsufficient for maintaining female fertility in the absence of ER and ERL1. Ovules of the haploinsufficient er-105 erl1-2 erl2-1/+ mutant exhibit abnormal development with reduced cell proliferation in the integuments and gametophyte abortion. Our analysis indicates that progression of integument growth requires ER-family signaling in a dosage-dependent manner and that transcriptional compensation among ER-family members occurs to maintain the required signaling threshold. The specific misregulation of cyclin A genes in the er-105 erl1-2 erl2-1/+ mutant suggests that downstream targets of the ER-signaling pathway might include these core cell-cycle regulators. Finally, genetic interaction of the ER family and the WOX-family gene, PFS2, reveals their contribution to integument development through interrelated mechanisms. PMID:17652352

  3. Engineered zinc-finger proteins can compensate genetic haploinsufficiency by transcriptional activation of the wild-type allele: application to Willams-Beuren syndrome and supravalvular aortic stenosis.

    Science.gov (United States)

    Zhang, Pei; Huang, Angela; Morales-Ruiz, Manuel; Starcher, Barry C; Huang, Yan; Sessa, William C; Niklason, Laura E; Giordano, Frank J

    2012-11-01

    Williams-Beuren syndrome (WBS) and supravalvular aortic stenosis (SVAS) are genetic syndromes marked by the propensity to develop severe vascular stenoses. Vascular lesions in both syndromes are caused by haploinsufficiency of the elastin gene. We used these distinct genetic syndromes as models to evaluate the feasibility of using engineered zinc-finger protein transcription factors (ZFPs) to achieve compensatory expression of haploinsufficient genes by inducing augmented expression from the remaining wild-type allele. For complex genes with multiple splice variants, this approach could have distinct advantages over cDNA-based gene replacement strategies. Targeting the elastin gene, we show that transcriptional activation by engineered ZFPs can induce compensatory expression from the wild-type allele in the setting of classic WBS and SVAS genetic mutations, increase elastin expression in wild-type cells, induce expression of the major elastin splice variants, and recapitulate their natural stoichiometry. Further, we establish that transcriptional activation of the mutant allele in SVAS does not overcome nonsense-mediated decay, and thus ZFP-mediated transcriptional activation is not likely to induce production of a mutant protein, a crucial consideration. Finally, we show in bioengineered blood vessels that ZFP-mediated induction of elastin expression is capable of stimulating functional elastogenesis. Haploinsufficiency is a common mechanism of genetic disease. These findings have significant implications for WBS and SVAS, and establish that haploinsufficiency can be overcome by targeted transcriptional activation without inducing protein expression from the mutant allele.

  4. Familial glucocorticoid receptor haploinsufficiency by non-sense mediated mRNA decay, adrenal hyperplasia and apparent mineralocorticoid excess.

    Directory of Open Access Journals (Sweden)

    Jérôme Bouligand

    Full Text Available Primary glucocorticoid resistance (OMIM 138040 is a rare hereditary disease that causes a generalized partial insensitivity to glucocorticoid action, due to genetic alterations of the glucocorticoid receptor (GR. Investigation of adrenal incidentalomas led to the discovery of a family (eight affected individuals spanning three generations, prone to cortisol resistance, bilateral adrenal hyperplasia, arterial hypertension and hypokalemia. This phenotype exacerbated over time, cosegregates with the first heterozygous nonsense mutation p.R469[R,X] reported to date for the GR, replacing an arginine (CGA by a stop (TGA at amino-acid 469 in the second zinc finger of the DNA-binding domain of the receptor. In vitro, this mutation leads to a truncated 50-kDa GR lacking hormone and DNA binding capacity, devoid of hormone-dependent nuclear translocation and transactivation properties. In the proband's fibroblasts, we provided evidence for the lack of expression of the defective allele in vivo. The absence of detectable mutated GR mRNA was accompanied by a 50% reduction in wild type GR transcript and protein. This reduced GR expression leads to a significantly below-normal induction of glucocorticoid-induced target genes, FKBP5 in fibroblasts. We demonstrated that the molecular mechanisms of glucocorticoid signaling dysfunction involved GR haploinsufficiency due to the selective degradation of the mutated GR transcript through a nonsense-mediated mRNA Decay that was experimentally validated on emetine-treated propositus' fibroblasts. GR haploinsufficiency leads to hypertension due to illicit occupation of renal mineralocorticoid receptor by elevated cortisol rather than to increased mineralocorticoid production reported in primary glucocorticoid resistance. Indeed, apparent mineralocorticoid excess was demonstrated by a decrease in urinary tetrahydrocortisone-tetrahydrocortisol ratio in affected patients, revealing reduced glucocorticoid degradation by

  5. Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

    DEFF Research Database (Denmark)

    Mercader, Josep; Ribot, Joan; Murano, Incoronata;

    2009-01-01

    Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ-line haploinsufficiency of the pRb gene (Rb...... first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances. Key words: brown adipose tissue, white adipose tissue, energy metabolism, genetic animal model....... proliferator-activated receptor (PPAR) gamma as well as of genes involved in mitochondrial function, cAMP sensitivity, brown adipocyte determination and tissue vascularization in white adipose tissue depots. Furthermore, Rb(+/-) mice exhibited signs of enhanced activation of brown adipose tissue and higher...

  6. Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms.

    Science.gov (United States)

    Emadali, Anouk; Hoghoughi, Neda; Duley, Samuel; Hajmirza, Azadeh; Verhoeyen, Els; Cosset, Francois-Loic; Bertrand, Philippe; Roumier, Christophe; Roggy, Anne; Suchaud-Martin, Céline; Chauvet, Martine; Bertrand, Sarah; Hamaidia, Sieme; Rousseaux, Sophie; Josserand, Véronique; Charles, Julie; Templier, Isabelle; Maeda, Takahiro; Bruder-Costa, Juliana; Chaperot, Laurence; Plumas, Joel; Jacob, Marie-Christine; Bonnefoix, Thierry; Park, Sophie; Gressin, Remy; Tensen, Cornelis P; Mecucci, Cristina; Macintyre, Elizabeth; Leroux, Dominique; Brambilla, Elisabeth; Nguyen-Khac, Florence; Luquet, Isabelle; Penther, Dominique; Bastard, Christian; Jardin, Fabrice; Lefebvre, Christine; Garnache, Francine; Callanan, Mary B

    2016-06-16

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive leukemia for which knowledge on disease mechanisms and effective therapies are currently lacking. Only a handful of recurring genetic mutations have been identified and none is specific to BPDCN. In this study, through molecular cloning in an index case that presented a balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, we identify monoallelic deletion of NR3C1 (5q31), encoding the glucocorticoid receptor (GCR), in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including 10 with NR3C1 deletion, did not reveal NR3C1 point mutations or indels. Haploinsufficiency for NR3C1 defined a subset of BPDCN with lowered GCR expression and extremely poor overall survival (P = .0006). Consistent with a role for GCR in tumor suppression, functional analyses coupled with gene expression profiling identified corticoresistance and loss-of-EZH2 function as major downstream consequences of NR3C1 deletion in BPDCN. Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion of NR3C1 to a long noncoding RNA (lncRNA) gene (lincRNA-3q) that encodes a novel, nuclear, noncoding RNA involved in the regulation of leukemia stem cell programs and G1/S transition, via E2F. Overexpression of lincRNA-3q was a consistent feature of malignant cells and could be abrogated by bromodomain and extraterminal domain (BET) protein inhibition. Taken together, this work points to NR3C1 as a haploinsufficient tumor suppressor in a subset of BPDCN and identifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN. PMID:27060168

  7. A large-scale complex haploinsufficiency-based genetic interaction screen in Candida albicans: analysis of the RAM network during morphogenesis.

    Directory of Open Access Journals (Sweden)

    Nike Bharucha

    2011-04-01

    Full Text Available The morphogenetic transition between yeast and filamentous forms of the human fungal pathogen Candida albicans is regulated by a variety of signaling pathways. How these pathways interact to orchestrate morphogenesis, however, has not been as well characterized. To address this question and to identify genes that interact with the Regulation of Ace2 and Morphogenesis (RAM pathway during filamentation, we report the first large-scale genetic interaction screen in C. albicans.Our strategy for this screen was based on the concept of complex haploinsufficiency (CHI. A heterozygous mutant of CBK1(cbk1Δ/CBK1, a key RAM pathway protein kinase, was subjected to transposon-mediated, insertional mutagenesis. The resulting double heterozygous mutants (6,528 independent strains were screened for decreased filamentation on SpiderMedium (SM. From the 441 mutants showing altered filamentation, 139 transposon insertion sites were sequenced,yielding 41 unique CBK1-interacting genes. This gene set was enriched in transcriptional targets of Ace2 and, strikingly, the cAMP-dependent protein kinase A (PKA pathway, suggesting an interaction between these two pathways. Further analysis indicates that the RAM and PKA pathways co-regulate a common set of genes during morphogenesis and that hyperactivation of the PKA pathway may compensate for loss of RAM pathway function. Our data also indicate that the PKA–regulated transcription factor Efg1 primarily localizes to yeast phase cells while the RAM–pathway regulated transcription factor Ace2 localizes to daughter nuclei of filamentous cells, suggesting that Efg1 and Ace2 regulate a common set of genes at separate stages of morphogenesis. Taken together, our observations indicate that CHI–based screening is a useful approach to genetic interaction analysis in C. albicans and support a model in which these two pathways regulate a common set of genes at different stages of filamentation.

  8. Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A

    Energy Technology Data Exchange (ETDEWEB)

    Nobukuni, Yoshitaka; Watanabe, A.; Takeda, Kazushisa; Skarka, Hana; Tachibana, Masayoshi [National Inst. of Health, Bethesda, MD (United States)

    1996-07-01

    Waardenburg syndrome type 2 (WS2) is a dominantly inherited disorder characterized by a pigmentation anomaly and hearing impairment due to lack of melanocyte. Previous work has linked a subset of families with WS2 (WS2A) to the MITF gene that encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif and that is involved in melanocyte differentiation. Several splice-site and missense mutations have been reported in individuals affected with WS2A. In this report, we have identified two novel point mutations in the MITF gene in affected individuals from two different families with WS2A. The two mutations (C760{r_arrow}T and C895{r_arrow}T) create stop codons in exons 7 and 8, respectively. Corresponding mutant alleles predict the truncated proteins lacking HLH-Zip or Zip structure. To understand how these mutations cause WS2 in heterozygotes, we generated mutant MITF cDNAs and used them for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose the DNA-binding activity and fail to transactivate the promoter of tyrosinase, a melanocyte-specific enzyme. However, these mutated proteins do not appear to interfere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the phenotypes of the two families with WS2A in the present study are caused by loss-of-function mutations in one of the two alleles of the MITF gene, resulting in haploinsufficiency of the MITF protein, the protein necessary for normal development of melanocytes. 37 refs., 4 figs.

  9. p27 kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation.

    Science.gov (United States)

    Zhou, Ningtian; Fu, Yuxuan; Wang, Yunle; Chen, Pengsheng; Meng, Haoyu; Guo, Shouyu; Zhang, Min; Yang, Zhijian; Ge, Yingbin

    2014-08-07

    p27(kip1) (p27) is widely known as a potent cell cycle inhibitor in several organs, especially in the heart. However, its role has not been fully defined during the early phase of myocardial infarction (MI). In this study, we investigated the relationships between p27, vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) and NF-κB in post-MI cardiac function repair both in vivo and in the hypoxia/ischemia-induced rat myocardiocyte model. In vivo, haplo-insufficiency of p27 improved cardiac function, diminished the infarct zone, protected myocardiocytes and increased angiogenesis by enhancing the production of VEGF/HGF. In vitro, the presence of conditioned medium from hypoxia/ischemia-induced p27 knockdown myocardiocytes reduced the injury caused by hypoxia/ischemia in myocardiocytes, and this effect was reversed by VEGF/HGF neutralizing antibodies, consistent with the cardioprotection being due to VEGF/HGF secretion. We also observed that p27 bound to IKK and that p27 haplo-insufficiency promoted IKK/p65 activation both in vivo and in vitro, thereby inducing the NF-κB downstream regulator, VEGF/HGF. Furthermore, IKKi and IKK inhibitor negated the effect of VEGF/HGF. Therefore, we conclude that p27 haplo-insufficiency protects against heart injury by VEGF/HGF mediated cardioprotection and increased angiogenesis through promoting IKK activation.

  10. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early onset autoinflammatory syndrome

    Science.gov (United States)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M.; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J.; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T.; Zaal, Kristien; Chandrasekharappa, Settara C.; Hanson, Eric P.; Yu, Zhen; Mullikin, James C.; Hasni, Sarfaraz A.; Wertz, Ingrid; Ombrello, Amanda K.; Stone, Deborah L.; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K.; Leavis, Helen L.; van Royen-Kerkof, Annet; Sibley, Cailin; Batu, Ezgi D.; Gül, Ahmet; Siegel, Richard M.; Boehm, Manfred; Milner, Joshua D.; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M.; Kastner, Daniel L.; Aksentijevich, Ivona

    2016-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity1. Herein we describe a new syndrome caused by high penetrance heterozygous germline mutations in the NFκB regulatory protein TNFAIP3 (A20) in six unrelated families with early onset systemic inflammation. The syndrome resembles Behçet’s disease (BD), which is typically considered a polygenic disorder with onset in early adulthood2. A20 is a potent inhibitor of the NFκB signaling pathway3. TNFAIP3 mutant truncated proteins are likely to act by haploinsufficiency since they do not exert a dominant-negative effect in overexpression experiments. Patients’ cells show increased degradation of IκBα and nuclear translocation of NFκB p65, and increased expression of NFκB-mediated proinflammatory cytokines. A20 restricts NFκB signals via deubiquitinating (DUB) activity. In cells expressing the mutant A20 protein, there is defective removal of K63-linked ubiquitin from TRAF6, NEMO, and RIP1 after TNF stimulation. NFκB-dependent pro-inflammatory cytokines are potential therapeutic targets for these patients. PMID:26642243

  11. Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors

    Directory of Open Access Journals (Sweden)

    Michael Feyder

    2007-12-01

    Full Text Available There is compelling evidence that L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA glutamate receptors containing the GluR1 subunit contribute to the molecular mechanisms associated with learning. AMPA GluR1 glutamate receptor knockout mice (KO exhibit abnormal hippocampal and amygdala plasticity, and deficits on various assays for cognition including Pavlovian fear conditioning. Here we examined associative fear learning in mice with complete absence (KO or partial loss (heterozygous mutant, HET of GluR1 on multiple fear conditioning paradigms. After multi-trial delay or trace conditioning, KO displayed impaired tone and context fear recall relative to WT, whereas HET were normal. After one-trial delay conditioning, both KO and HET showed impaired tone and context recall. HET and KO showed normal nociceptive sensitivity in the hot plate and tail flick tests. These data demonstrate that the complete absence of GluR1 subunit-containing receptors prevents the formation of associative fear memories, while GluR1 haploinsufficiency is sufficient to impair one-trial fear learning. These findings support growing evidence of a major role for GluR1-containing AMPA receptors in amygdalamediated forms of learning and memory.

  12. Antagonizing pathways leading to differential dynamics in colon carcinogenesis in Shugoshin1 (Sgo1)-haploinsufficient chromosome instability model.

    Science.gov (United States)

    Rao, Chinthalapally V; Sanghera, Saira; Zhang, Yuting; Biddick, Laura; Reddy, Arun; Lightfoot, Stan; Dai, Wei; Yamada, Hiroshi Y

    2016-05-01

    Colon cancer is the second most lethal cancer. It is predicted to claim 50,310 lives in 2014. Chromosome Instability (CIN) is observed in 80-90% of colon cancers, and is thought to contribute to colon cancer progression and recurrence. However, there are no animal models of CIN that have been validated for studies of colon cancer development or drug testing. In this study, we sought to validate a mitotic error-induced CIN model mouse, the Shugoshin1 (Sgo1) haploinsufficient mouse, as a colon cancer study model. Wild-type and Sgo1(-/+) mice were treated with the colonic carcinogen, azoxymethane (AOM). We tracked colon tumor development 12, 24, and 36 wk after treatment to assess progression of colon tumorigenesis. Initially, more precancerous lesions, Aberrant Crypt Foci (ACF), developed in Sgo1(-/+) mice. However, the ACF did not develop straightforwardly into larger tumors. At the 36-wk endpoint, the number of gross tumors in Sgo1(-/+) mice was no different from that in wild-type controls. However, Copy Number Variation (CNV) analysis indicated that fully developed colon tumor in Sgo1(-/+) mice carried 13.75 times more CNV. Immunohistological analyses indicated that Sgo1(-/+) mice differentially expressed IL-6, Bcl2, and p16(INK4A) . We propose that formation of ACF in Sgo1(-/+) mice is facilitated by the IL6-STAT3-SOCS3 oncogenic pathway and by the Bcl2-anti-apoptotic pathway, yet further development of the ACF to tumors is inhibited by the p16(INK4A) tumor suppressor pathway. Manipulating these pathways would be beneficial for inhibiting development of colon cancer with CIN. © 2015 Wiley Periodicals, Inc. PMID:25773652

  13. Haploinsufficiency of SF-1 Causes Female to Male Sex Reversal in Nile Tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Xie, Qing-Ping; He, Xue; Sui, Yi-Ning; Chen, Li-Li; Sun, Li-Na; Wang, De-Shou

    2016-06-01

    Steroidogenic factor-1 (Sf-1) (officially designated nuclear receptor subfamily 5 group A member 1 [NR5A1]) is a master regulator of steroidogenesis and reproduction in mammals. However, its function remains unclear in nonmammalian vertebrates. In the present study, we used immunohistochemistry to detect expression of Sf-1 in the steroidogenic cells, the interstitial, granulosa, and theca cells of the ovary, and the Leydig cells of the testis, in Nile tilapia. Clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (Cas9) cleavage of sf-1 resulted in a high mutation rate in the F0 generation and a phenotype of gonadal dysgenesis and reduced steroidogenic cells in XX and XY fish. Sf-1 deficiency also resulted in decreased cytochrome P450, family 19, subfamily A, polypeptide 1a, forkhead box L2 expression, and serum estradiol-17β in XX fish. In XY fish, Sf-1 deficiency increased cytochrome P450, family 19, subfamily A, polypeptide 1a and forkhead box L2 expression but decreased cytochrome P450, family 11, subfamily B, polypeptide 2 expression and serum 11-ketotestosterone levels. 17α-methyltestosterone treatment successfully rescued the gonadal phenotype of Sf-1-deficient XY fish, as demonstrated by normal spermatogenesis and production of F1 mutants. In contrast, estradiol-17β treatment only partially rescued the gonadal phenotype of Sf-1-deficient XX fish, as demonstrated by the appearance of phase II oocytes. Furthermore, both sf-1(+/-) F1 XX and XY mutants developed as fertile males, although spermatogenesis was delayed and efferent duct formation was disordered. Our data suggest that Sf-1 is a major regulator of steroidogenesis and reproduction in fish, as it is in mammals. Sf-1 deficiency resulted in gonadal dysgenesis and feminization of XY gonads. However, unlike in mammals, Sf-1 deficiency also resulted in female to male sex reversal in 8.1% of F0 and 92.1% of sf-1(+/-) F1 in XX fish.

  14. Haploinsufficiency of SF-1 Causes Female to Male Sex Reversal in Nile Tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Xie, Qing-Ping; He, Xue; Sui, Yi-Ning; Chen, Li-Li; Sun, Li-Na; Wang, De-Shou

    2016-06-01

    Steroidogenic factor-1 (Sf-1) (officially designated nuclear receptor subfamily 5 group A member 1 [NR5A1]) is a master regulator of steroidogenesis and reproduction in mammals. However, its function remains unclear in nonmammalian vertebrates. In the present study, we used immunohistochemistry to detect expression of Sf-1 in the steroidogenic cells, the interstitial, granulosa, and theca cells of the ovary, and the Leydig cells of the testis, in Nile tilapia. Clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (Cas9) cleavage of sf-1 resulted in a high mutation rate in the F0 generation and a phenotype of gonadal dysgenesis and reduced steroidogenic cells in XX and XY fish. Sf-1 deficiency also resulted in decreased cytochrome P450, family 19, subfamily A, polypeptide 1a, forkhead box L2 expression, and serum estradiol-17β in XX fish. In XY fish, Sf-1 deficiency increased cytochrome P450, family 19, subfamily A, polypeptide 1a and forkhead box L2 expression but decreased cytochrome P450, family 11, subfamily B, polypeptide 2 expression and serum 11-ketotestosterone levels. 17α-methyltestosterone treatment successfully rescued the gonadal phenotype of Sf-1-deficient XY fish, as demonstrated by normal spermatogenesis and production of F1 mutants. In contrast, estradiol-17β treatment only partially rescued the gonadal phenotype of Sf-1-deficient XX fish, as demonstrated by the appearance of phase II oocytes. Furthermore, both sf-1(+/-) F1 XX and XY mutants developed as fertile males, although spermatogenesis was delayed and efferent duct formation was disordered. Our data suggest that Sf-1 is a major regulator of steroidogenesis and reproduction in fish, as it is in mammals. Sf-1 deficiency resulted in gonadal dysgenesis and feminization of XY gonads. However, unlike in mammals, Sf-1 deficiency also resulted in female to male sex reversal in 8.1% of F0 and 92.1% of sf-1(+/-) F1 in XX fish. PMID:27046435

  15. Flt-1 haploinsufficiency ameliorates muscular dystrophy phenotype by developmentally increased vasculature in mdx mice

    OpenAIRE

    Verma, Mayank; Asakura, Yoko; Hirai, Hiroyuki; Watanabe, Shuichi; Tastad, Christopher; Fong, Guo-Hua; Ema, Masatsugu; Call, Jarrod A.; Lowe, Dawn A.; Asakura, Atsushi

    2010-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene coding for the protein dystrophin. Recent work demonstrates that dystrophin is also found in the vasculature and its absence results in vascular deficiency and abnormal blood flow. This induces a state of ischemia further aggravating the muscular dystrophy pathogenesis. For an effective form of therapy of DMD, both the muscle and the vasculature need to be addressed. To reveal the develo...

  16. Haploinsufficiency in the prometastasis Kiss1 Receptor Gpr54 delays breast tumor initiation, progression and lung metastasis

    Science.gov (United States)

    Cho, Sung-Gook; Wang, Ying; Rodriguez, Melissa; Tan, Kunrong; Zhang, Wenzheng; Luo, Jian; Li, Dali; Liu, Mingyao

    2016-01-01

    Activation of KISS1 receptor (KISS1R or GPR54) by its ligands (kisspeptins) regulates a diverse function both in normal physiology and pathophysiology. In cancer, KISS1-induced KISS1R signaling is known to inhibit tumor angiogenesis and metastasis. However, roles of KISS1 and KISS1R in earlier stages of tumor progression and metastasis in vivo are still unknown. In this study, we demonstrate a critical role for Kiss1r in early stages of tumor progression using mouse tumor models. PyMT/Kiss1r mice with different Kiss1r genotypes were obtained by crossing MMTV-PyMT transgenic mouse with Kiss1r heterozygous mouse (Kiss1r+/−). Kiss1r heterozygosity attenuated breast tumor initiation, growth, latency, multiplicity and metastasis in MMTV-PyMT/Kiss1r+/− mouse models. To confirm the effects of Kiss1r in tumor progression and limit any effect of endogenous hormones, we isolated primary tumor cells from PyMT/Kiss1r+/+ or PyMT/Kiss1r+/− mice and performed in vitro and in vivo tumorigenesis assays. Kiss1r heterozygosity inhibited PyMT-induced in vitro tumorigeneity and in vivo tumor growth in NOD.SCID/NCr mice. To understand the underlying mechanism, we showed that activation of KISS1R by kisspeptin-10 led to RhoA activation and RhoA-dependent gene expression through Gαq-p63RhoGEF signaling pathway. Furthermore, anchorage-independent growth was tightly linked to the dosage-dependent regulation of RhoA by KISS1R. When MCF10A cells overexpressing H-RasV12 were subjected to in vitro tumorigenesis assays, knockdown of KISS1R or inactivation of RhoA in MCF10A cells reduced Ras-induced anchorage-independent growth, similar to our data obtained from PyMT-Kiss1r+/− mouse models. Altogether, we conclude that Kiss1r haploinsufficiency delays breast tumor initiation, progression and metastasis through its downstream Gαq-p63RhoGEF-RhoA signaling pathway. PMID:21852382

  17. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    Directory of Open Access Journals (Sweden)

    Ullrich Stephen E

    2011-01-01

    Full Text Available Abstract Background The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. Methods UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. Results UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19 translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. Conclusion UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal

  18. Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.

    Directory of Open Access Journals (Sweden)

    Kim M Gerecke

    Full Text Available Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF, have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/- with strain-matched wild-type (WT mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.

  19. Rad21-cohesin haploinsufficiency impedes DNA repair and enhances gastrointestinal radiosensitivity in mice.

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    Huiling Xu

    Full Text Available Approximately half of cancer-affected patients receive radiotherapy (RT. The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were identified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR-mediated gene targeting and sister chromatid exchanges. Rad21+/- animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI. Importantly, Rad21+/- animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues.

  20. Prenatal Diagnosis of Cystic Hygroma related to a Deletion of 16q24.1 with Haploinsufficiency of FOXF1 and FOXC2 Genes

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    Matthew J. Garabedian

    2012-01-01

    Full Text Available We report the prenatal diagnosis of cystic hygroma that was subsequently identified to have haploinsufficiency of the FOXF1 and FOXC2 genes via array comparative genomic hybridization (aCGH. Deletion o f these genes has previously neither been associated with cystic hygroma nor prenatally diagnosed. The FOX gene cluster is involved in cardiopulmonary development. This case expands the phenotypic spectrum o f abnormalities of the FOXF1 and FOXC2 genes, as it seems within the spectrum of function that disruption of the FOX gene cluster would lead to include abnormalities of prenatal onset. Identification of this association would not be possible with conventional karyotype or targeted aCGH. This case highlights the power of whole genomic aCGH to further delineate the etiology of birth defects.

  1. Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1

    DEFF Research Database (Denmark)

    Tibelius, Alexandra; Marhold, Joachim; Zentgraf, Hanswalter;

    2009-01-01

    Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPD II) are disorders exhibiting marked microcephaly, with small brain sizes reflecting reduced neuron production during fetal life. Although primary microcephaly can be caused by mutations...

  2. The HSP90 inhibitor NVP-AUY922 radiosensitizes by abrogation of homologous recombination resulting in mitotic entry with unresolved DNA damage.

    Directory of Open Access Journals (Sweden)

    Shane Zaidi

    Full Text Available Heat shock protein 90 (HSP90 is a molecular chaperone responsible for the conformational maintenance of a number of client proteins that play key roles in cell cycle arrest, DNA damage repair and apoptosis following radiation. HSP90 inhibitors exhibit antitumor activity by modulating the stabilisation and activation of HSP90 client proteins. We sought to evaluate NVP-AUY922, the most potent HSP90 inhibitor yet reported, in preclinical radiosensitization studies.NVP-AUY922 potently radiosensitized cells in vitro at low nanomolar concentrations with a concurrent depletion of radioresistance-linked client proteins. Radiosensitization by NVP-AUY922 was verified for the first time in vivo in a human head and neck squamous cell carcinoma xenograft model in athymic mice, as measured by delayed tumor growth and increased surrogate end-point survival (p = <0.0001. NVP-AUY922 was shown to ubiquitously inhibit resolution of dsDNA damage repair correlating to delayed Rad51 foci formation in all cell lines tested. Additionally, NVP-AUY922 induced a stalled mitotic phenotype, in a cell line-dependent manner, in HeLa and HN5 cell lines irrespective of radiation exposure. Cell cycle analysis indicated that NVP-AUY922 induced aberrant mitotic entry in all cell lines tested in the presence of radiation-induced DNA damage due to ubiquitous CHK1 depletion, but resultant downstream cell cycle effects were cell line dependent.These results identify NVP-AUY922 as the most potent HSP90-mediated radiosensitizer yet reported in vitro, and for the first time validate it in a clinically relevant in vivo model. Mechanistic analysis at clinically achievable concentrations demonstrated that radiosensitization is mediated by the combinatorial inhibition of cell growth and survival pathways, ubiquitous delay in Rad51-mediated homologous recombination and CHK1-mediated G(2/M arrest, but that the contribution of cell cycle perturbation to radiosensitization may be cell line

  3. Haploinsufficiency of SOX5, a member of the SOX (SRY-related HMG-box) family of transcription factors is a cause of intellectual disability.

    Science.gov (United States)

    Schanze, Ina; Schanze, Denny; Bacino, Carlos A; Douzgou, Sofia; Kerr, Bronwyn; Zenker, Martin

    2013-02-01

    Intellectual disability (ID) is a clinically and genetically heterogeneous condition; the cause is unknown in most non-specific and sporadic cases. To establish an etiological basis in those patients represents a difficult challenge. Over the last years it has become apparent that chromosomal rearrangements below the detection level of conventional karyotyping contribute significantly to the cause of ID. We present three patients with non-specific intellectual disability who all have overlapping microdeletions in the chromosomal region 12p12.1. De novo occurrence of the deletion could be proven in the two cases from which parental samples were available. All three identified deletions have different breakpoints and range in size from 120 kb to 4.9 Mb. The smallest deletion helps to narrow down the critical region to a genomic segment (chr12:23,924,800-24,041,698, build 37/hg19) encompassing only one gene, SOX5. SOX5 is a member of the SOX (SRY-related HMG-box) family of transcription factors shown to play roles in chondroblast function, oligodendrocyte differentiation and migration, as well as ensuring proper development of specific neuronal cell types. Because of these biological functions, mutations in SOX5 are predicted to cause complex disease syndromes, as it is the case for other SOX genes, but such mutations have not yet been identified. Our findings indicate that haploinsufficiency of SOX5 is a cause of intellectual disability without any striking physical anomalies.

  4. Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity.

    Science.gov (United States)

    Witteveen, Josefine S; Willemsen, Marjolein H; Dombroski, Thaís C D; van Bakel, Nick H M; Nillesen, Willy M; van Hulten, Josephus A; Jansen, Eric J R; Verkaik, Dave; Veenstra-Knol, Hermine E; van Ravenswaaij-Arts, Conny M A; Wassink-Ruiter, Jolien S Klein; Vincent, Marie; David, Albert; Le Caignec, Cedric; Schieving, Jolanda; Gilissen, Christian; Foulds, Nicola; Rump, Patrick; Strom, Tim; Cremer, Kirsten; Zink, Alexander M; Engels, Hartmut; de Munnik, Sonja A; Visser, Jasper E; Brunner, Han G; Martens, Gerard J M; Pfundt, Rolph; Kleefstra, Tjitske; Kolk, Sharon M

    2016-08-01

    Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development. PMID:27399968

  5. Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome.

    Science.gov (United States)

    Han, Joan C; Thurm, Audrey; Golden Williams, Christine; Joseph, Lisa A; Zein, Wadih M; Brooks, Brian P; Butman, John A; Brady, Sheila M; Fuhr, Shannon R; Hicks, Melanie D; Huey, Amanda E; Hanish, Alyson E; Danley, Kristen M; Raygada, Margarita J; Rennert, Owen M; Martinowich, Keri; Sharp, Stephen J; Tsao, Jack W; Swedo, Susan E

    2013-01-01

    In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of variable size near the BDNF locus and can serve as a model for studying human BDNF haploinsufficiency (+/-). We hypothesized that BDNF+/- would be associated with more severe cognitive impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) received neurocognitive assessments. Deletion boundaries for the subjects in the WAGR group were determined by high-resolution oligonucleotide array comparative genomic hybridization. Within the WAGR group, BDNF+/- subjects (n = 15), compared with BDNF intact (+/+) subjects (n = 13), had lower adaptive behaviour (p = .02), reduced cognitive functioning (p = .04), higher levels of reported historical (p = .02) and current (p = .02) social impairment, and higher percentage meeting cut-off score for autism (p = .047) on Autism Diagnostic Interview-Revised. These differences remained nominally significant after adjusting for visual acuity. Using diagnostic measures and clinical judgement, 3 subjects (2 BDNF+/- and 1 BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. A comparison group of visually impaired subjects with isolated aniridia had cognitive functioning comparable to that of healthy controls. In summary, among subjects with WAGR syndrome, BDNF+/- subjects had a mean Vineland Adaptive Behaviour Compose score that was 14-points lower and a mean intelligence quotient (IQ) that was 20-points lower than BDNF+/+ subjects. Our findings support the hypothesis that BDNF plays an important role in human neurocognitive development.

  6. RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Azamat Aslanukov

    2006-10-01

    Full Text Available The Ran-binding protein 2 (RanBP2 is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/- are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/- mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

  7. Altered Cortical Dynamics and Cognitive Function upon Haploinsufficiency of the Autism-Linked Excitatory Synaptic Suppressor MDGA2.

    Science.gov (United States)

    Connor, Steven A; Ammendrup-Johnsen, Ina; Chan, Allen W; Kishimoto, Yasushi; Murayama, Chiaki; Kurihara, Naokazu; Tada, Atsushi; Ge, Yuan; Lu, Hong; Yan, Ryan; LeDue, Jeffrey M; Matsumoto, Hirotaka; Kiyonari, Hiroshi; Kirino, Yutaka; Matsuzaki, Fumio; Suzuki, Toshiharu; Murphy, Timothy H; Wang, Yu Tian; Yamamoto, Tohru; Craig, Ann Marie

    2016-09-01

    Mutations in a synaptic organizing pathway contribute to autism. Autism-associated mutations in MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) are thought to reduce excitatory/inhibitory transmission. However, we show that mutation of Mdga2 elevates excitatory transmission, and that MDGA2 blocks neuroligin-1 interaction with neurexins and suppresses excitatory synapse development. Mdga2(+/-) mice, modeling autism mutations, demonstrated increased asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, with no change in measures of inhibitory synapses. Behavioral assays revealed an autism-like phenotype including stereotypy, aberrant social interactions, and impaired memory. In vivo voltage-sensitive dye imaging, facilitating comparison with fMRI studies in autism, revealed widespread increases in cortical spontaneous activity and intracortical functional connectivity. These results suggest that mutations in MDGA2 contribute to altered cortical processing through the dual disadvantages of elevated excitation and hyperconnectivity, and indicate that perturbations of the NRXN-NLGN pathway in either direction from the norm increase risk for autism. PMID:27608760

  8. GABAergic neuron deficit as an idiopathic generalized epilepsy mechanism: the role of BRD2 haploinsufficiency in juvenile myoclonic epilepsy.

    Directory of Open Access Journals (Sweden)

    Libor Velíšek

    Full Text Available Idiopathic generalized epilepsy (IGE syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/- mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/- males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/- female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/- vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/- mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR, yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/- mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i sex-specific increases in seizure susceptibility, ii the development of spontaneous seizures, and iii seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE.

  9. Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes

    Directory of Open Access Journals (Sweden)

    Johnson Jennifer M

    2005-06-01

    proliferation or deficient differentiation potential in breast epithelial cells from this patient which might have contributed to her cancer susceptibility. Although NER deficiency has been demonstrated repeatedly in blood samples from sporadic breast cancer patients, analysis of blood cultured lymphocytes and breast epithelial cells for this patient proves definitively that heterozygosity for inactivation of BRCA1 does not intrinsically confer this type of genetic instability. These data suggest that the mechanism of genomic instability driving the carcinogenic process may be fundamentally different in hereditary and sporadic breast cancer, resulting in different genotoxic susceptibilities, oncogene mutations, and a different molecular pathogenesis.

  10. Is activation of the intra-S checkpoint in human fibroblasts an important factor in protection against UV-induced mutagenesis?

    Science.gov (United States)

    Sproul, Christopher D; Rao, Shangbang; Ibrahim, Joseph G; Kaufmann, William K; Cordeiro-Stone, Marila

    2013-11-15

    The ATR/CHK1-dependent intra-S checkpoint inhibits replicon initiation and replication fork progression in response to DNA damage caused by UV (UV) radiation. It has been proposed that this signaling cascade protects against UV-induced mutations by reducing the probability that damaged DNA will be replicated before it can be repaired. Normal human fibroblasts (NHF) were depleted of ATR or CHK1, or treated with the CHK1 kinase inhibitor TCS2312, and the UV-induced mutation frequency at the HPRT locus was measured. Despite clear evidence of S-phase checkpoint abrogation, neither ATR/CHK1 depletion nor CHK1 inhibition caused an increase in the UV-induced HPRT mutation frequency. These results question the premise that the UV-induced intra-S checkpoint plays a prominent role in protecting against UV-induced mutagenesis.

  11. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    International Nuclear Information System (INIS)

    Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  12. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Heekyoung [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Yoon, Su Jin [Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Jin, Juyoun [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Choi, Seung Ho [Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Seol, Ho Jun; Lee, Jung-Il [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); and others

    2011-03-04

    Research highlights: {yields} The most important therapeutic tool in brain metastasis is radiation therapy. {yields} Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. {yields} Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. {yields} Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  13. The SHOX gene and the short stature. Roundtable on diagnosis and treatment of short stature due to SHOX haploinsufficiency: how genetics, radiology and anthropometry can help the pediatrician in the diagnostic process Padova (April 20th, 2011).

    Science.gov (United States)

    De Sanctis, Vincenzo; Tosetto, Ilaria; Iughetti, Lorenzo; Antoniazzi, Franco; Clementi, Maurizio; Toffolutti, Tiziana; Facchin, Paola; Monti, Elena; Pisanello, Lorena; Tonini, Giorgio; Greggio, Nella A

    2012-08-01

    The growth of the human body depends from a complex interaction between nutritional, environmental and hormonal factors and by a large number of different genes. One of these genes, short stature homeobox (SHOX), is believed to play a major role in growth. SHOX haploinsufficiency is associated with a wide spectrum of conditions, all characterized growth failure such as Leri-Weill dyschondrosteosis, Turner syndrome, short stature with subtle auxological and radiological findings and the so called "idiopathic short stature" (short stature with no specific findings other than growth failure). The document was prepared by a multidisciplinary team (paediatric endocrinologists, paediatrician, radiologist, geneticist and epidemiologist) to focus on the investigation of children with suspected SHOX- deficiency (SHOX-D) for an early identification and a correct diagnostic work - up of this genetic disorder. On the basis of a number of screening studies, SHOX-D appears to be a relatively frequent cause of short stature. The following recommendations were suggested by our multidisciplinary team: (i) a careful family history, measurements of body proportions and detection of any dysmorphic features are important for the suspect of a genetic disorder ,(ii)the presence of any combination of the following physical findings, such as reduced arm span/height ratio, increased sitting height/height ratio, above average BMI, Madelung deformity, cubitus valgus, short or bowed forearm, dislocation of the ulna at the elbow, or the appearance of muscular hypertrophy, should prompt the clinician to obtain a molecular analysis of the SHOX region, (iii) it is of practical importance to recognise early or mild signs of Madelung deformity on hand and wrist radiographs, (iv) growth hormone ,after stimulation test, is usually normal. However, treatment with rhGH may improve final adult height; the efficacy of treatment is similar to that observed in those treated for Turner syndrome. PMID

  14. A protein kinase a-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency.

    NARCIS (Netherlands)

    Tamma, G.; Lasorsa, D.; Trimpert, C.; Ranieri, M.; Mise, A. Di; Mola, M.G.; Mastrofrancesco, L.; Devuyst, O.; Svelto, M.; Deen, P.M.T.; Valenti, G.

    2014-01-01

    Renal water reabsorption is controlled by arginine vasopressin (AVP), which binds to V2 receptors, resulting in protein kinase A (PKA) activation, phosphorylation of aquaporin 2 (AQP2) at serine 256, and translocation of AQP2 to the plasma membrane. However, AVP also causes dephosphorylation of AQP2

  15. Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/− or Rb1+/− backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling

    Science.gov (United States)

    Almeida, Madson Q.; Muchow, Michael; Boikos, Sosipatros; Bauer, Andrew J.; Griffin, Kurt J.; Tsang, Kit Man; Cheadle, Chris; Watkins, Tonya; Wen, Feng; Starost, Matthew F.; Bossis, Ioannis; Nesterova, Maria; Stratakis, Constantine A.

    2010-01-01

    PRKAR1A inactivation leads to dysregulated cAMP signaling and Carney complex (CNC) in humans, a syndrome associated with skin, endocrine and other tumors. The CNC phenotype is not easily explained by the ubiquitous cAMP signaling defect; furthermore, Prkar1a+/− mice did not develop skin and other CNC tumors. To identify whether a Prkar1a defect is truly a generic but weak tumorigenic signal that depends on tissue-specific or other factors, we investigated Prkar1a+/− mice when bred within the Rb1+/− or Trp53+/− backgrounds, or treated with a two-step skin carcinogenesis protocol. Prkar1a+/− Trp53+/− mice developed more sarcomas than Trp53+/− mice (P < 0.05) and Prkar1a+/− Rb1+/− mice grew more (and larger) pituitary and thyroid tumors than Rb1+/− mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Prkar1a+/− mice also developed more papillomas than wild-type animals. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling, along with cell cycle abnormalities; all changes were confirmed by qRT–PCR array and immunohistochemistry. siRNA down-regulation of Ctnnb1, E2f1 or Cdk4 inhibited proliferation of human adrenal cells bearing a PRKAR1A-inactivating mutation and Prkar1a+/− mouse embryonic fibroblasts and arrested both cell lines at the G0/G1 phase of the cell cycle. In conclusion, Prkar1a haploinsufficiency is a relatively weak tumorigenic signal that can act synergistically with other tumor suppressor gene defects or chemicals to induce tumors, mostly through Wnt-signaling activation and cell cycle dysregulation, consistent with studies in human neoplasms carrying PRKAR1A defects. PMID:20080939

  16. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Directory of Open Access Journals (Sweden)

    Kim Nuytens

    Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  17. Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome

    Directory of Open Access Journals (Sweden)

    J. Hsiao

    2016-07-01

    Full Text Available Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT. Using oligonucleotide-based compounds (AntagoNATs targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.

  18. Haploinsufficiency of the E3 ubiquitin ligase C-terminus of heat shock cognate 70 interacting protein (CHIP produces specific behavioral impairments.

    Directory of Open Access Journals (Sweden)

    Bethann McLaughlin

    Full Text Available The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and

  19. Haploinsufficiency of Dmxl2, Encoding a Synaptic Protein, Causes Infertility Associated with a Loss of GnRH Neurons in Mouse

    Science.gov (United States)

    Jacquier, Sandrine; Csaba, Zsolt; Genin, Emmanuelle; Meyer, Vincent; Leka, Sofia; Dupont, Joelle; Charles, Perrine; Chevenne, Didier; Carel, Jean-Claude; Léger, Juliane; de Roux, Nicolas

    2014-01-01

    Characterization of the genetic defects causing gonadotropic deficiency has made a major contribution to elucidation of the fundamental role of Kisspeptins and Neurokinin B in puberty onset and reproduction. The absence of puberty may also reveal neurodevelopmental disorders caused by molecular defects in various cellular pathways. Investigations of these neurodevelopmental disorders may provide information about the neuronal processes controlling puberty onset and reproductive capacity. We describe here a new syndrome observed in three brothers, which involves gonadotropic axis deficiency, central hypothyroidism, peripheral demyelinating sensorimotor polyneuropathy, mental retardation, and profound hypoglycemia, progressing to nonautoimmune insulin-dependent diabetes mellitus. High-throughput sequencing revealed a homozygous in-frame deletion of 15 nucleotides in DMXL2 in all three affected patients. This homozygous deletion was associated with lower DMXL2 mRNA levels in the blood lymphocytes of the patients. DMXL2 encodes the synaptic protein rabconnectin-3α, which has been identified as a putative scaffold protein for Rab3-GAP and Rab3-GEP, two regulators of the GTPase Rab3a. We found that rabconnectin-3α was expressed in exocytosis vesicles in gonadotropin-releasing hormone (GnRH) axonal extremities in the median eminence of the hypothalamus. It was also specifically expressed in cells expressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) within the pituitary. The conditional heterozygous deletion of Dmxl2 from mouse neurons delayed puberty and resulted in very low fertility. This reproductive phenotype was associated with a lower number of GnRH neurons in the hypothalamus of adult mice. Finally, Dmxl2 knockdown in an insulin-secreting cell line showed that rabconnectin-3α controlled the constitutive and glucose-induced secretion of insulin. In conclusion, this study shows that low levels of DMXL2 expression cause a complex neurological

  20. Haploinsufficiency of Dmxl2, encoding a synaptic protein, causes infertility associated with a loss of GnRH neurons in mouse.

    Directory of Open Access Journals (Sweden)

    Brooke Tata

    2014-09-01

    Full Text Available Characterization of the genetic defects causing gonadotropic deficiency has made a major contribution to elucidation of the fundamental role of Kisspeptins and Neurokinin B in puberty onset and reproduction. The absence of puberty may also reveal neurodevelopmental disorders caused by molecular defects in various cellular pathways. Investigations of these neurodevelopmental disorders may provide information about the neuronal processes controlling puberty onset and reproductive capacity. We describe here a new syndrome observed in three brothers, which involves gonadotropic axis deficiency, central hypothyroidism, peripheral demyelinating sensorimotor polyneuropathy, mental retardation, and profound hypoglycemia, progressing to nonautoimmune insulin-dependent diabetes mellitus. High-throughput sequencing revealed a homozygous in-frame deletion of 15 nucleotides in DMXL2 in all three affected patients. This homozygous deletion was associated with lower DMXL2 mRNA levels in the blood lymphocytes of the patients. DMXL2 encodes the synaptic protein rabconnectin-3α, which has been identified as a putative scaffold protein for Rab3-GAP and Rab3-GEP, two regulators of the GTPase Rab3a. We found that rabconnectin-3α was expressed in exocytosis vesicles in gonadotropin-releasing hormone (GnRH axonal extremities in the median eminence of the hypothalamus. It was also specifically expressed in cells expressing luteinizing hormone (LH and follicle-stimulating hormone (FSH within the pituitary. The conditional heterozygous deletion of Dmxl2 from mouse neurons delayed puberty and resulted in very low fertility. This reproductive phenotype was associated with a lower number of GnRH neurons in the hypothalamus of adult mice. Finally, Dmxl2 knockdown in an insulin-secreting cell line showed that rabconnectin-3α controlled the constitutive and glucose-induced secretion of insulin. In conclusion, this study shows that low levels of DMXL2 expression cause a

  1. Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe

    OpenAIRE

    Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C.

    2007-01-01

    As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expres...

  2. Short Hairpin RNA Suppression of Thymidylate Synthase Produces DNA Mismatches and Results in Excellent Radiosensitization

    Energy Technology Data Exchange (ETDEWEB)

    Flanagan, Sheryl A., E-mail: sflan@umich.edu [Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Cooper, Kristin S. [Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Mannava, Sudha; Nikiforov, Mikhail A. [Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York (United States); Shewach, Donna S. [Department of Pharmacology, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2012-12-01

    Purpose: To determine the effect of short hairpin ribonucleic acid (shRNA)-mediated suppression of thymidylate synthase (TS) on cytotoxicity and radiosensitization and the mechanism by which these events occur. Methods and Materials: shRNA suppression of TS was compared with 5-fluoro-2 Prime -deoxyuridine (FdUrd) inactivation of TS with or without ionizing radiation in HCT116 and HT29 colon cancer cells. Cytotoxicity and radiosensitization were measured by clonogenic assay. Cell cycle effects were measured by flow cytometry. The effects of FdUrd or shRNA suppression of TS on dNTP deoxynucleotide triphosphate imbalances and consequent nucleotide misincorporations into deoxyribonucleic acid (DNA) were analyzed by high-pressure liquid chromatography and as pSP189 plasmid mutations, respectively. Results: TS shRNA produced profound ({>=}90%) and prolonged ({>=}8 days) suppression of TS in HCT116 and HT29 cells, whereas FdUrd increased TS expression. TS shRNA also produced more specific and prolonged effects on dNTPs deoxynucleotide triphosphates compared with FdUrd. TS shRNA suppression allowed accumulation of cells in S-phase, although its effects were not as long-lasting as those of FdUrd. Both treatments resulted in phosphorylation of Chk1. TS shRNA alone was less cytotoxic than FdUrd but was equally effective as FdUrd in eliciting radiosensitization (radiation enhancement ratio: TS shRNA, 1.5-1.7; FdUrd, 1.4-1.6). TS shRNA and FdUrd produced a similar increase in the number and type of pSP189 mutations. Conclusions: TS shRNA produced less cytotoxicity than FdUrd but was equally effective at radiosensitizing tumor cells. Thus, the inhibitory effect of FdUrd on TS alone is sufficient to elicit radiosensitization with FdUrd, but it only partially explains FdUrd-mediated cytotoxicity and cell cycle inhibition. The increase in DNA mismatches after TS shRNA or FdUrd supports a causal and sufficient role for the depletion of dTTP thymidine triphosphate and consequent DNA

  3. Enceladus Results

    Data.gov (United States)

    National Aeronautics and Space Administration — Here are some results from the Spectra Decomposition Algorithm on infrared spectral images of Saturn's moon Enceladus. Figure 1 is the spatial contribution of the...

  4. Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure-based design and optimization of thiophenecarboxamide ureas.

    Science.gov (United States)

    Oza, Vibha; Ashwell, Susan; Almeida, Lynsie; Brassil, Patrick; Breed, Jason; Deng, Chun; Gero, Thomas; Grondine, Michael; Horn, Candice; Ioannidis, Stephanos; Liu, Dongfang; Lyne, Paul; Newcombe, Nicholas; Pass, Martin; Read, Jon; Ready, Shannon; Rowsell, Siân; Su, Mei; Toader, Dorin; Vasbinder, Melissa; Yu, Dingwei; Yu, Yan; Xue, Yafeng; Zabludoff, Sonya; Janetka, James

    2012-06-14

    Checkpoint kinases CHK1 and CHK2 are activated in response to DNA damage that results in cell cycle arrest, allowing sufficient time for DNA repair. Agents that lead to abrogation of such checkpoints have potential to increase the efficacy of such compounds as chemo- and radiotherapies. Thiophenecarboxamide ureas (TCUs) were identified as inhibitors of CHK1 by high throughput screening. A structure-based approach is described using crystal structures of JNK1 and CHK1 in complex with 1 and 2 and of the CHK1-3b complex. The ribose binding pocket of CHK1 was targeted to generate inhibitors with excellent cellular potency and selectivity over CDK1and IKKβ, key features lacking from the initial compounds. Optimization of 3b resulted in the identification of a regioisomeric 3-TCU lead 12a. Optimization of 12a led to the discovery of the clinical candidate 4 (AZD7762), which strongly potentiates the efficacy of a variety of DNA-damaging agents in preclinical models. PMID:22551018

  5. Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anti-cancer therapies

    Science.gov (United States)

    Matthews, Thomas P; Jones, Alan M; Collins, Ian

    2014-01-01

    Introduction Checkpoint kinase inhibitors offer the promise of enhancing the effectiveness of widely prescribed cancer chemotherapies and radiotherapy by inhibiting the DNA damage response, as well as the potential for single agent efficacy. Areas covered This article surveys structural insights into the checkpoint kinases CHK1 and CHK2 that have been exploited to enhance the selectivity and potency of small molecule inhibitors. The use of mechanistic cellular assays to guide the optimisation of inhibitors is reviewed. The status of the current clinical candidates and emerging new clinical contexts for CHK1 and CHK2 inhibitors are discussed, including the prospects for single agent efficacy. Expert opinion Protein bound water molecules play key roles in structural features that can be targeted to gain high selectivity for either enzyme. The results of early phase clinical trials of checkpoint inhibitors have been mixed, but significant progress has been made in testing the combination of CHK1 inhibitors with genotoxic chemotherapy. Second generation CHK1 inhibitors are likely to benefit from increased selectivity and oral bioavailability. While the optimum therapeutic context for CHK2 inhibition remains unclear, the emergence of single agent preclinical efficacy for CHK1 inhibitors in specific tumour types exhibiting constitutive replication stress represents exciting progress in exploring the therapeutic potential of these agents. PMID:23594139

  6. Disruption of the Sec24d gene results in early embryonic lethality in the mouse.

    Directory of Open Access Journals (Sweden)

    Andrea C Baines

    Full Text Available Transport of newly synthesized proteins from the endoplasmic reticulum (ER to the Golgi is mediated by the coat protein complex COPII. The inner coat of COPII is assembled from heterodimers of SEC23 and SEC24. Though mice with mutations in one of the four Sec24 paralogs, Sec24b, exhibit a neural tube closure defect, deficiency in humans or mice has not yet been described for any of the other Sec24 paralogs. We now report characterization of mice with targeted disruption of Sec24d. Early embryonic lethality is observed in mice completely deficient in SEC24D, while a hypomorphic Sec24d allele permits survival to mid-embryogenesis. Mice haploinsufficient for Sec24d exhibit no phenotypic abnormality. A BAC transgene containing Sec24d rescues the embryonic lethality observed in Sec24d-null mice. These results demonstrate an absolute requirement for SEC24D expression in early mammalian development that is not compensated by the other three Sec24 paralogs. The early embryonic lethality resulting from loss of SEC24D in mice contrasts with the previously reported mild skeletal phenotype of SEC24D deficiency in zebrafish and restricted neural tube phenotype of SEC24B deficiency in mice. Taken together, these observations suggest that the multiple Sec24 paralogs have developed distinct functions over the course of vertebrate evolution.

  7. Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice.

    Directory of Open Access Journals (Sweden)

    Michelle Goldsworthy

    Full Text Available We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7 gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes died during embryonic development at 9.5-14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level.

  8. Elastin Haploinsufficiency Induces Alternative Aging Processes in the Aorta

    OpenAIRE

    Pezet, Mylène; Jacob, Marie-Paule; Escoubet, Brigitte; Gheduzzi, Dealba; Tillet, Emmanuelle; Perret, Pascale; Huber, Philippe; Quaglino, Daniela; Vranckx, Roger; Li, Dean Y.; Starcher, Barry; Boyle, Walter A.; Mecham, Robert P.; Faury, Gilles

    2008-01-01

    Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosi...

  9. Transketolase Haploinsufficiency Reduces Adipose Tissue and Female Fertility in Mice

    OpenAIRE

    Xu, Zheng-Ping; Wawrousek, Eric F.; Piatigorsky, Joram

    2002-01-01

    Transketolase (TKT) is a ubiquitous enzyme used in multiple metabolic pathways. We show here by gene targeting that TKT-null mouse embryos are not viable and that disruption of one TKT allele can cause growth retardation (≈35%) and preferential reduction of adipose tissue (≈77%). Other TKT+/− tissues had moderate (≈33%; liver, gonads) or relatively little (≈7 to 18%; eye, kidney, heart, brain) reductions in mass. These mice expressed a normal level of growth hormone and reduced leptin levels....

  10. Haploinsufficiency of glutamine synthetase increases susceptibility to experimental febrile seizures.

    NARCIS (Netherlands)

    Gassen, K.L.I. van; Hel, W.S. van der; Hakvoort, T.B.; Lamers, W.H.; Graan, P.N. de

    2009-01-01

    Glutamine synthetase (GS) is a pivotal glial enzyme in the glutamate-glutamine cycle. GS is important in maintaining low extracellular glutamate concentrations and is downregulated in the hippocampus of temporal lobe epilepsy patients with mesial-temporal sclerosis, an epilepsy syndrome that is freq

  11. Haploinsufficiency of glutamine synthetase increases susceptibility to experimental febrile seizures

    NARCIS (Netherlands)

    K.L.I. van Gassen; W.S. van der Hel; T.B.M. Hakvoort; W.H. Lamers; P.N.E. de Graan

    2009-01-01

    Glutamine synthetase (GS) is a pivotal glial enzyme in the glutamate-glutamine cycle. GS is important in maintaining low extracellular glutamate concentrations and is downregulated in the hippocampus of temporal lobe epilepsy patients with mesial-temporal sclerosis, an epilepsy syndrome that is freq

  12. 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...

  13. Haploinsufficiency of TAB2 Causes Congenital Heart Defects in Humans

    NARCIS (Netherlands)

    B. Thienpont; L. Zhang; A.V. Postma; J. Breckpot; L.C. Tranchevent; P. van Loo; K. Møllgård; N. Tommerup; I. Bache; Z. Tümer; K. van Engelen; B. Menten; G. Mortier; D. Waggoner; M. Gewillig; Y. Moreau; K. Devriendt; L.A. Larsen

    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

  14. Haploinsufficiency of TAB2 causes congenital heart defects in humans

    DEFF Research Database (Denmark)

    Thienpont, Bernard; Zhang, Litu; Postma, Alex V;

    2010-01-01

    in cardiac development was further supported by its conserved expression in the developing human and zebrafish heart. Moreover, a critical, dosage-sensitive role during development was demonstrated by the cardiac defects observed upon titrated knockdown of tab2 expression in zebrafish embryos......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...... demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development....

  15. Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo.

    Science.gov (United States)

    Qi, Wenxiu; Zhang, Wenbo; Edwards, Holly; Chu, Roland; Madlambayan, Gerard J; Taub, Jeffrey W; Wang, Zhihong; Wang, Yue; Li, Chunhuai; Lin, Hai; Ge, Yubin

    2015-01-01

    MK-1775 is the first-in-class selective Wee1 inhibitor which has been demonstrated to synergize with CHK1 inhibitors in various malignancies. In this study, we report that the pan-histone deacetylase inhibitor (HDACI) panobinostat synergizes with MK-1775 in acute myeloid leukemia (AML), a malignancy which remains a clinical challenge and requires more effective therapies. Using both AML cell line models and primary patient samples, we demonstrated that panobinostat and MK-1775 synergistically induced proliferation arrest and cell death. We also demonstrated that panobinostat had equal anti-leukemic activities against primary AML blasts derived from patients either at initial diagnosis or at relapse. Interestingly, treatment with panobinostat alone or in combination with MK-1775 resulted in decreased Wee1 protein levels as well as downregulation of the CHK1 pathway. shRNA knockdown of CHK1 significantly sensitized AML cells to MK-1775 treatment, while knockdown of Wee1 significantly enhanced both MK-1775- and panobinostat-induced cell death. Our results demonstrate that panobinostat synergizes with MK-1775 in AML cells, at least in part through downregulation of CHK1 and/or Wee1, providing compelling evidence for the clinical development of the combination treatment in AML. PMID:26529495

  16. In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Xiaodong Gao

    2016-05-01

    Full Text Available Checkpoint kinase 1 (Chk1 is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure–activity relationship (3D-QSAR modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q2 values (0.531, 0.726, fitted correlation r2 coefficients (higher than 0.90, and standard error of prediction (less than 0.250. These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

  17. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation.

    Directory of Open Access Journals (Sweden)

    Neel M Fofaria

    Full Text Available In this study, we determined the cytotoxic effects of piperine, a major constituent of black and long pepper in melanoma cells. Piperine treatment inhibited the growth of SK MEL 28 and B16 F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine correlated with the down-regulation of cyclin D1 and induction of p21. Furthermore, this growth arrest by piperine treatment was associated with DNA damage as indicated by phosphorylation of H2AX at Ser139, activation of ataxia telangiectasia and rad3-related protein (ATR and checkpoint kinase 1 (Chk1. Pretreatment with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Similarly, transfection of cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine. Piperine treatment caused down-regulation of E2F1 and phosphorylation of retinoblastoma protein (Rb. Apoptosis induced by piperine was associated with down-regulation of XIAP, Bid (full length and cleavage of Caspase-3 and PARP. Furthermore, our results showed that piperine treatment generated ROS in melanoma cells. Blocking ROS by tiron protected the cells from piperine mediated cell cycle arrest and apoptosis. These results suggest that piperine mediated ROS played a critical role in inducing DNA damage and activation of Chk1 leading to G1 cell cycle arrest and apoptosis.

  18. Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R

    Directory of Open Access Journals (Sweden)

    Liang Dong

    2010-07-01

    Full Text Available Abstract Background Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. Results To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU and ultraviolet light (UV also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. Conclusions These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

  19. Role of swi7H4 mutant allele of DNA polymerase α in the DNA damage checkpoint response.

    Directory of Open Access Journals (Sweden)

    Saman Khan

    Full Text Available Besides being a mediator of initiation of DNA replication, DNA polymerase α plays a key role in chromosome maintenance. Swi7H4, a novel temperature sensitive mutant of DNA polymerase α was shown to be defective in transcriptional silencing at the mating type centromere and telomere loci. It is also required for the establishment of chromatin state that can recruit the components of the heterochromatin machinery at these regions. Recently the role of DNA polymerase α in the S-phase alkylation damage response in S. pombe has also been studied. Here we investigate whether defects generated by swi7H4, a mutant allele of DNA polymerase α can activate a checkpoint response. We show that swi7H4 exhibit conditional synthetic lethality with chk1 null mutant and the double mutant of swi7H4 with chk1 deletion aggravate the chromosome segregation defects. More importantly swi7H4 mutant cells delay the mitotic progression at non permissive temperature that is mediated by checkpoint protein kinase Chk1. In addition we show that, in the swi7H4 mutant background, cells accumulate DNA damage at non permissive temperature activating the checkpoint kinase protein Chk1. Further, we observed synthetic lethality between swi7H4 and a number of genes involved in DNA repair pathway at semi permissive temperature. We summarize that defects in swi7H4 mutant results in DNA damage that delay mitosis in a Chk1 dependent manner that also require the damage repair pathway for proper recovery.

  20. RESULTS RESULTING FROM AUTOFRETTAGE OF CYLINDER

    Institute of Scientific and Technical Information of China (English)

    ZHU Ruilin

    2008-01-01

    Autofrettage is used to introduce advantageous residual stresses into wall of a cylinder and to even distributions of total stresses. Basic theory on autofrettage has been functioning for several decades. It is necessary to reveal profound relations between parameters in the theory. Therefore, based on the 3rd strength theory, δei/δy, δei/δy, δei′/δy, δei′/δy and their relations, as well as p/δy, are studied under ideal conditions, where δei/δy is equivalent stress of total stresses at elastoplastic juncture/yield strength, δei/δy is equivalent stress of total stresses at inside surface/yield strength, δei′/δy is equivalent stress of residual stresses at elastoplastic juncture/yield strength, δei′/δy is equivalent stress of residual stresses at inside surface/yield strength, p/δy is load-bearing capacity of an autofrettaged cylinder/yield strength. Theoretical study on the parameters results in noticeable results and laws. The main idea is: to satisfy |δei′|=δy, the relation between kj and k is , where k is outside/inside radius ratio of a cylinder, kj is ratio of elastoplastic juncture radius to inside radius of a cylinder; when the plastic region covers the whole wall of a cylinder, for compressive yield not to occur after removing autofrettage pressure, the ultimate k is k=2.218 46, with k=2.218 46, a cylinder's ultimate load-bearing capacity equals its entire yield pressure, or =lnk; when kj≤=1.648 72, no matter how great k is, compressive yield never occurs after removing pa; the maximum and optimum load-bearing capacity of an autofrettaged cylinder is just two times the loading which an unautofrettaged cylinder can bear elastically, or , thus the limit of the load-bearing capacity of an autofrettaged cylinder is also just 2 times that of an unautofrettaged cylinder.

  1. Total 2004 results

    International Nuclear Information System (INIS)

    This document presents the 2004 results of Total Group: consolidated account, special items, number of shares, market environment, adjustment for amortization of Sanofi-Aventis merger-related intangibles, 4. quarter 2004 results (operating and net incomes, cash flow), upstream (results, production, reserves, recent highlights), downstream (results, refinery throughput, recent highlights), chemicals (results, recent highlights), Total's full year 2004 results (operating and net income, cash flow), 2005 sensitivities, Total SA parent company accounts and proposed dividend, adoption of IFRS accounting, summary and outlook, main operating information by segment for the 4. quarter and full year 2004: upstream (combined liquids and gas production by region, liquids production by region, gas production by region), downstream (refined product sales by region, chemicals), Total financial statements: consolidated statement of income, consolidated balance sheet (assets, liabilities and shareholder's equity), consolidated statements of cash flows, business segments information. (J.S.)

  2. Total 2004 results

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-02-01

    This document presents the 2004 results of Total Group: consolidated account, special items, number of shares, market environment, adjustment for amortization of Sanofi-Aventis merger-related intangibles, 4. quarter 2004 results (operating and net incomes, cash flow), upstream (results, production, reserves, recent highlights), downstream (results, refinery throughput, recent highlights), chemicals (results, recent highlights), Total's full year 2004 results (operating and net income, cash flow), 2005 sensitivities, Total SA parent company accounts and proposed dividend, adoption of IFRS accounting, summary and outlook, main operating information by segment for the 4. quarter and full year 2004: upstream (combined liquids and gas production by region, liquids production by region, gas production by region), downstream (refined product sales by region, chemicals), Total financial statements: consolidated statement of income, consolidated balance sheet (assets, liabilities and shareholder's equity), consolidated statements of cash flows, business segments information. (J.S.)

  3. Recent results from KTEV

    Energy Technology Data Exchange (ETDEWEB)

    Bellantoni, L.; /Fermilab

    2005-06-01

    The implications of the published KTeV K{sub L}{sup 0} {yields} {pi}{sup 0}{mu}{sup +}{mu}{sup -} result for interpreting recent {Sigma}{sup +} {yields} p{mu}{sup +} {mu}{sup -} results are discussed. The status of the KTeV {Xi}{sup 0} {yields} {Sigma}{sup +} {mu}{sup -}{nu} analysis is given. The KTeV |V{sub us}| result is also given.

  4. Results from SAGE

    CERN Document Server

    Vermul, V M; Bowles, T J; Cherry, M L; Cleveland, B T; Davis, R; Elliott, S R; Gavrin, V N; Girin, S V; Gorbachev, V V; Ibragimova, T V; Kalikhov, A V; Khairnasov, N G; Knodel, T V; Lande, K; Mirmov, I N; Nico, J S; Shikhin, A A; Teasdale, W A; Veretenkin, E P; Vermul, V M; Wark, D L; Wildenhain, P S; Wilkerson, J F; Yants, V E; Zatsepin, G T

    2002-01-01

    We report the results of 11 years of solar neutrino observation by the Russian-American Gallium solar neutrino Experiment (SAGE). The overall result of 84 runs during the measurement period January 1990 through March 2001 is 75.6 +5.9/-5.8 (stat.) +3.5/-3.0 (syst.) SNU. This represents only slightly more than half of the predicted standard solar model rate of 129 SNU. The individual results of each run, as well as the results of combined analysis of all runs are presented.

  5. Results from SAGE

    Energy Technology Data Exchange (ETDEWEB)

    Vermul, V.M.; Abdurashitov, J.N.; Bowles, T.J.; Cherry, M.L.; Cleveland, B.T.; Davis, R.; Elliott, S.R.; Gavrin, V.N.; Girin, S.V.; Gorbachev, V.V.; Ibragimova, T.V.; Kalikhov, A.V.; Khairnasov, N.G.; Knodel, T.V.; Lande, K.; Mirmov, I.N.; Nico, J.S.; Shikhin, A.A.; Teasdale, W.A.; Veretenkin, E.P.; Wark, D.L.; Wildenhain, P.S.; Wilkerson, J.F.; Yants, V.E.; Zatsepin, G.T

    2002-07-01

    We report the results of 11 years of solar neutrino observation by the Russian-American Gallium solar neutrino Experiment (SAGE). The overall result of 84 runs during the measurement period January 1990 through March 2001 is 75.6 +5.9/-5.8 (stat.) +3.5/-3.0 (syst.) SNU. This represents only slightly more than half of the predicted standard solar model rate of 129 SNU. The individual results of each run, as well as the results of combined analysis of all runs are presented.

  6. New results from COMPASS

    CERN Document Server

    Kabuß, Eva-Maria

    2015-01-01

    An overview on recent COMPASS results is given, including the extraction of the longitudinal spin structure functions interpreted with a NLO QCD fit, new results on the gluon polarisation and a measurement of pion and kaon multiplicities with a LO extraction of quark-to-hadron fragmentation functions

  7. Annual results 2004

    International Nuclear Information System (INIS)

    This 2004 annual evaluation of the french RTE company (electric power transport network) provides information on the 2004 results on: institutional information, financial results, customers and market, industrial resources, environment and consultation, human resources and international aspects. (A.L.B.)

  8. Duration and Results (PECODR

    Directory of Open Access Journals (Sweden)

    Martin Dawes

    2007-01-01

    Conclusions Results suggest a PECODR-related structure exists in medical abstracts and that there might be lexical patterns specific to these elements. More sophisticated computer-assisted lexical-semantic analysis might refine these results, and pave the way to automating PECODR indexing, and improve information retrieval in primary care.

  9. Recent results from TRISTAN

    Energy Technology Data Exchange (ETDEWEB)

    Enomoto, Ryoji [National Laboratory for High Energy Physics, Ibaraki (Japan)

    1997-01-01

    TRISTAN results on {gamma}{gamma} physics from 1994 to 1995 are reviewed in this report. We have systematically investigated jet production, the {gamma}-structure function, and charm pair production in {gamma}{gamma} processes. The results are discussed, and future prospects are presented.

  10. Gene expression patterns in heterozygous Plk4 murine embryonic fibroblasts

    Directory of Open Access Journals (Sweden)

    Nantais Jordan

    2009-07-01

    Full Text Available Abstract Background The polo-like kinases (Plks are a group of serine/threonine kinases which have roles in many aspects of cellular function including the regulation of mitotic activity and cellular stress responses. This study focuses on Plk4, the most divergent member of the Plk family, which is necessary for proper cellular proliferation. More specifically, alterations in Plk4 levels cause significantly adverse mitotic defects including abnormal centrosome duplication and aberrant mitotic spindle formation. We sought to clarify the effect of reduced Plk4 levels on the cell by examining transcript profiles of Plk4 wild-type and heterozygous mouse embryonic fibroblasts (MEFs. Subsequently, the levels of several key proteins involved in the DNA damage response were examined. Results 143 genes were found to be significantly up-regulated in the heterozygous MEFs compared to their wild-type counterparts, while conversely, 9 genes were down-regulated. Numerous genes with increased transcript levels in heterozygous MEFs were identified to be involved in p53-dependent pathways. Furthermore, examination of the promoter regions of all up- and down-regulated genes revealed that the majority contained putative p53 responsive elements. An analysis of transcript levels in MEFs after exposure to either ionizing or ultraviolet radiation revealed a significant change between wild type and heterozygous MEFS for Plk4 transcript levels upon only UV exposure. Furthermore, changes in protein levels of several important cell check-point and apoptosis regulators were examined, including p53, Chk1, Chk2, Cdc25C and p21. In heterozygous MEFs, p53, p21 and Chk2 protein levels were at significantly higher levels. Furthermore, p53 activity was increased 5 fold in the Plk4 heterozygous MEFs. Conclusion Global transcript profiles and levels of key proteins involved in cellular proliferation and DNA damage pathways were examined in wild-type and Plk4 heterozygous MEFs. It

  11. Ibis DDT test results

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document contains test results from a study done to determine the organochlorine levels in the livers of white-faced ibis from Stillwater Wildlife Management...

  12. Gene expression results

    Data.gov (United States)

    U.S. Environmental Protection Agency — qPCR results for Vitellogenin This dataset is associated with the following publication: Armstrong, B., J. Lazorchak , K. Jensen , H. Haring , M.E. Smith, R. Flick...

  13. Atmospheric Deposition Modeling Results

    Data.gov (United States)

    U.S. Environmental Protection Agency — This asset provides data on model results for dry and total deposition of sulfur, nitrogen and base cation species. Components include deposition velocities, dry...

  14. Microenterprise Results Reporting

    Data.gov (United States)

    US Agency for International Development — Microenterprise Results Reporting (MRR) is an annual report to the U.S. Congress providing funding and program data on USAID's microenterprise activities. The MRR...

  15. Transacsys PLC - Final Results

    CERN Multimedia

    2002-01-01

    Final results from Transacsys PLC. A subsidary of this company was set up to develop the CERN EDH system into a commercial product but incurred too much financial loss so the project was cancelled (1/2 page).

  16. Haiti DevResults

    Data.gov (United States)

    US Agency for International Development — DevResults is a web-based portfolio management system that tracks program data for the Haiti Mission that was awarded in April of 2013. (The Mozambique and/or...

  17. Cholesterol testing and results

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000386.htm Cholesterol testing and results To use the sharing features ... can tell you what your goal should be. Cholesterol Tests Some cholesterol is considered good and some ...

  18. ATLAS physics results

    CERN Document Server

    AUTHOR|(CDS)2074312

    2015-01-01

    The ATLAS experiment at the Large Hadron Collider at CERN has been successfully taking data since the end of 2009 in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV, and in heavy ion collisions. In these lectures, some of the most recent ATLAS results will be given on Standard Model measurements, the discovery of the Higgs boson, searches for supersymmetry and exotics and on heavy-ion results.

  19. Combining Affymetrix microarray results

    Directory of Open Access Journals (Sweden)

    Doerge RW

    2005-03-01

    Full Text Available Abstract Background As the use of microarray technology becomes more prevalent it is not unusual to find several laboratories employing the same microarray technology to identify genes related to the same condition in the same species. Although the experimental specifics are similar, typically a different list of statistically significant genes result from each data analysis. Results We propose a statistically-based meta-analytic approach to microarray analysis for the purpose of systematically combining results from the different laboratories. This approach provides a more precise view of genes that are significantly related to the condition of interest while simultaneously allowing for differences between laboratories. Of particular interest is the widely used Affymetrix oligonucleotide array, the results of which are naturally suited to a meta-analysis. A simulation model based on the Affymetrix platform is developed to examine the adaptive nature of the meta-analytic approach and to illustrate the usefulness of such an approach in combining microarray results across laboratories. The approach is then applied to real data involving a mouse model for multiple sclerosis. Conclusion The quantitative estimates from the meta-analysis model tend to be closer to the "true" degree of differential expression than any single lab. Meta-analytic methods can systematically combine Affymetrix results from different laboratories to gain a clearer understanding of genes' relationships to specific conditions of interest.

  20. Higgs Results from CMS

    Science.gov (United States)

    Bornheim, Adolf

    2014-03-01

    The Nobel Prize in physics 2013 has been awarded to François Englert and Peter W. Higgs for the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles which plays a crucial role in our understanding of electro-weak symmetry breaking. I will review the experimental results manifesting the discovery of the so called Higgs boson from the perspective of the Compact Muon Solenoid (CMS) collaboration. The review is based on the final results from the proton-proton collision data at 7 TeV and 8 TeV center-of-mass energy, collected in 2011 and 2012 in the initial run of the Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN). Results on the properties of the new particle with a mass around 125 GeV, all in agreement with the expectations for the Standard Model (SM) Higgs boson, are highlighted. Latest results on the couplings between the Higgs and fermionic fields, in particular the final results of searches for a Higgs boson decaying into a b-quark or a tau-lepton pair, are presented. Non-SM Higgs searches are briefly summarized. Future perspectives for Higgs physics with CMS at LHC for the next data taking period starting in 2015 and beyond are discussed. CMS Collaboration.

  1. Total 2003 Results

    International Nuclear Information System (INIS)

    This document presents the 2003 results of Total Group: consolidated account, special items, number of shares, market environment, 4. quarter 2003 results, full year 2003 results, upstream (key figures, proved reserves), downstream key figures, chemicals key figures, parent company accounts and proposed dividends, 2004 sensitivities, summary and outlook, operating information by segment for the 4. quarter and full year 2003: upstream (combined liquids and gas production by region, liquids production by region, gas production by region), downstream (refinery throughput by region, refined product sales by region, chemicals), impact of allocating contribution of Cepsa to net operating income by business segment: equity in income (loss) and affiliates and other items, Total financial statements: consolidated statement of income, consolidated balance sheet (assets, liabilities and shareholder's equity), consolidated statements of cash flows, business segments information. (J.S.)

  2. Recent results from PEP

    International Nuclear Information System (INIS)

    Preliminary results are presented for the data taken by the MARK II and MAC collaborations at the PEP storage ring. Results include measurements of QED processes, limits on the weak couplings g/sub V/ and g/sub A/, limits on anomalous lepton production, the measurement of the tau lifetime, scale violation in inclusive hadron production, Monte Carlo independent tests of QCD using energy-energy correlations and single jet energy moments, measurements of the properties of three jet events, and measurements of proton, neutral kaon, lambda and proton pair yields

  3. Recent results from PEP

    Energy Technology Data Exchange (ETDEWEB)

    Hollebeek, R.

    1981-10-01

    Preliminary results are presented for the data taken by the MARK II and MAC collaborations at the PEP storage ring. Results include measurements of QED processes, limits on the weak couplings g/sub V/ and g/sub A/, limits on anomalous lepton production, the measurement of the tau lifetime, scale violation in inclusive hadron production, Monte Carlo independent tests of QCD using energy-energy correlations and single jet energy moments, measurements of the properties of three jet events, and measurements of proton, neutral kaon, lambda and proton pair yields.

  4. Recent CMS Results

    OpenAIRE

    Dorigo, Tommaso

    2012-01-01

    The CMS experiment obtained a large number of groundbreaking results from the analysis of 7- and 8-TeV proton-proton collisions produced so far by the Large Hadron Collider at CERN. In this brief summary only a sample of those results will be discussed. A new particle with mass m(H) = 125.3 +- 0.4(stat.) +- 0.5(syst.) GeV and characteristics compatible with those expected for a standard model Higgs boson has been observed in its decays to photon pairs, WW pairs, and ZZ pairs. Searches for the...

  5. Recent CDF results

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Gervasio; /Cantabria Inst. of Phys.

    2007-11-01

    As of November of 2007, the CDF detector has recorded approximately 2.7 fb{sup -1} of data. This contribution describes some of the most recent and most relevant results from the CDF collaboration in all areas of its wide physics program, as well as some insights into the Tevatron reach for Higgs searches within the next few years.

  6. Quantitative QCD: recent results

    International Nuclear Information System (INIS)

    We discuss some recent results in the phenomenology of perturbative QCD. Special emphasis is put on the ambiguities of the theoretical predictions and on low they affect the determination of the physical parameters. Recent calculations concerning jet and photon production at large momentum transfer are reviewed and two examples of calculations in the next-to-next to leading logarithm approximation are mentioned. (author)

  7. Recent MILC spectrum results

    OpenAIRE

    Bernard, C.; Blum, T.; DeGrand, T. A.; DeTar, C.; Gottlieb, Steve; Heller, Urs M.; Hetrick, J.; McNeile, C.; K. Rummukainen(University of Helsinki, Helsinki, Finland); Sugar, R. L.; Toussaint, Doug; Wingate, M

    1996-01-01

    We report on results from three spectrum calculations with staggered quarks: 1) a quenched calculation with the standard action for the gluons and quarks; 2) a quenched calculation with improved actions for both the gluons and quarks; and 3) a calculation with two flavors of dynamical quarks using the standard actions for the gluons and quarks.

  8. Roadmap of Infinite Results

    DEFF Research Database (Denmark)

    Srba, Jiří

    2002-01-01

    This paper provides a comprehensive summary of equivalence checking results for infinite-state systems. References to the relevant papers will be updated continuously according to the development in the area. The most recent version of this document is available from the web-page http://www.brics.dk/~srba/roadmap....

  9. Chapter 5: Monitoring results

    DEFF Research Database (Denmark)

    Poel, Bart; Thomsen, Kirsten Engelund; Schultz, Jørgen Munthe

    2003-01-01

    The monitoring results from the IEA Task 13 project "Advanced solar low energy houses" are described in this chapter. The underlying information was collected in the form of questionnaires. The questionnaires were formulated in such a way that participants are provided with a uniform lay-out to f...

  10. Review of LEP results

    CERN Document Server

    Parodi, F

    2001-01-01

    I present a review of the results obtained during 10 years of activity in b-physics at LEP. Special emphasis is put on measurements that attained precisions not even envisaged at the beginning of the LEP programme (V/sub ub/ and Delta m/sub s/). Finally the impact of these measurements on the CKM parameters determination is presented. (16 refs).

  11. Top Quark Results

    CERN Document Server

    ATLAS collaboration; LHCb collaboration

    2016-01-01

    Measurements of top quarks from Run-I and Run-II of the LHC are presented. Results on differential and inclusive top quark production cross sections, measured by the ATLAS, CMS and LHCb experiments, and measurements of top quark properties and mass are reported.

  12. FLUCTUATION RESULTS FRO PHENIX.

    Energy Technology Data Exchange (ETDEWEB)

    MITCHELL, J.T.

    2005-04-21

    The PHENIX Experiment at the Relativistic Heavy Ion Collider has made measurements of event-by-event fluctuations in the net charge, the mean transverse momentum, and the charged particle multiplicity as a function of collision energy, centrality, and transverse momentum in heavy ion collisions. The results of these measurements will be reviewed and discussed.

  13. Final results from the $\

    CERN Document Server

    Vidal-Sitjes, G

    2001-01-01

    An updated analysis of the full NOMAD data corresponding to approx 1.35 x 10 sup 6 charged current interactions has been performed to search for neutrino oscillations through nu subtau appearance. This document updates the recently published results on the nu submu -> nu subtau and nu submu -> nu sub e oscillations search in NOMAD with a unified analysis of the hadronic channels.

  14. Copyright Survey Results.

    Science.gov (United States)

    Botterbusch, Hope R.

    1992-01-01

    Reports results of a survey of copyright concerns that was conducted by the Association for Educational Communications and Technology. Areas addressed include video and television; copyright legislation; printed materials; music; audiovisual materials; and computer software. A checklist of proper copyright procedures is included. (six references)…

  15. Solar results purchasing

    International Nuclear Information System (INIS)

    Solar Thermal water heating has made little market penetration in some European countries. The main barriers to market development are: Long payback periods for the technology; Difficulties for the end-user in meeting the initial capital costs of the installation; Lack of confidence in the delivered energy that can be expected from the technology. The third barrier has been addressed using the concept of Guaranteed Solar Results (GSR). This project has addressed the other two main barriers using the concept of Solar Results Purchasing, (SRP) which combines GSR with Third Party Financing. The work was carried out in the UK, France, and Spain. The project used a uniform approach across the three countries. Each team calculated solar performance using an English version of the SOLO programme developed by TECSOL in France to encode the methodology for GSR model contracts. (author)

  16. Recent results from HELIOS

    Directory of Open Access Journals (Sweden)

    Back B. B.

    2011-10-01

    Full Text Available Transfer and inelastic scattering reactions using light-ion beams and stable or long-lived targets have traditionally provided detailed information on the structure of nuclei near the line of beta stability. Such studies can now be extended to nuclei away from the line of β-stability as radioactive beams are becoming available at a number of facilities around the world, including the CARIBU facility at Argonne. These measurements must, however, be carried out in inverse kinematics, resulting in a loss of the effective experimental resolution when conventional detection schemes are employed. The HELIOS spectrometer is based on a new concept, that is especially well suited for such studies by reducing the resolution problem, providing simple particle identification, and giving high detection efficiency with moderate Si detector area. In this talk, the HELIOS concept and results from the first series of experiments will be presented.

  17. CLEO Results B Decays

    CERN Document Server

    Cassel, David G

    2001-01-01

    Measurements of many Standard Model constants are clouded by uncertainties in nonperturbative QCD parameters that relate measurable quantities to the underlying parton-level processes. Generally these QCD parameters have been obtained from model calculations with large uncertainties that are difficult to quantify. The CLEO Collaboration has taken a major step towards reducing these uncertainties in determining the CKM matrix elements Vcb and Vub using new measurements of the branching fraction and photon energy spectrum of B -> s gamma decays. This report includes: the new CLEO measurements of B -> s gamma decays, Vcb, and Vub; the first results from CLEO III data -- studies of B -> K pi, pi pi, and K Kbar decays; mention of some other recent CLEO B decay results; and plans for operating CESR and CLEO in the charm threshold region.

  18. RESULTS OF SLICE MEASUREMENTS

    CERN Document Server

    Rudolph, J

    2011-01-01

    The linear accelerator ELBE delivers high-brightness electron bunches to multiple user stations, including two IR-FEL oscillators [1], [2]. In the framework of an upgrade program the current thermionic injector is being replaced by a SRF-photoinjector [3], [4]. The SRF injector promises higher beam quality, especially required for future experiments with high power laser radiation. During the commissioning phase, the SRF-injector was running in parallel to the thermionic gun. After installation of a injection beamline (dogleg), beam from the SRF-injector can now be injected into the ELBE linac. Detailed characterization of the electron beam quality delivered by the new electron injector includes vertical slice emittance measurements in addition to measurements of projected emittance values. This report gives an overview of the status of the project and summarizes first measurement results as well as results of simulations performed with measurement settings.

  19. Recent results from CMS

    Directory of Open Access Journals (Sweden)

    Schöfbeck Robert

    2015-01-01

    Full Text Available The CMS experiment at the Large Hadron Collider at CERN collected a dataset of 19.5fb−1 during 8 TeV proton-proton operation. A large number of groundbreaking results were obtained from the analysis of this dataset, among them the discovery of the Higgs boson and precision measurements of important Standard Model parameters, for example the mass of the top quark. Subtle processes like the production of a Z boson by fusion of two W bosons have been measured for the first time. Moreover, many searches for physics beyond the Standard model have been carried out, both in the context of supersymmetry and beyond, which often provide tight constraints in model parameter space. This brief summary is a a short overview of the most important recent CMS results at 7 and 8 TeV.

  20. Dosimetric results on EURECA

    Energy Technology Data Exchange (ETDEWEB)

    Reitz, G.

    1995-02-01

    Detector packages were exposed on the European Retrievable Carrier (EURECA) as part of the Biostack experiment inside the Exobiology and Radiation Assembly (ERA) and at several locations around EURECA. The packages consist of different plastic nuclear track detectors, nuclear emulsions and thermoluminescence dosimeters (TLD`s). Evaluation of these detectors yields data on absorbed dose and particle and LET spectra. Preliminary results of absorbed dose measurements in the EURECA dosimeter packages are reported and compared to results of the LDEF experiments. The highest dose rate measured on EURECA is 63.3 plus or minus 0.4 mGy d(exp -1) behind a shielding thickness of 0.09 g cm(exp -2) in front of the detector package.

  1. Neutrino mass: Recent results

    International Nuclear Information System (INIS)

    Some recent developments in the experimental search for neutrino mass are discussed. Simpson and Hime report finding new evidence for a 17-keV neutrino in the β decay of 3H and 35S. New data from Los Alamos on the electron neutrino mass as measured in tritium beta decay give an upper limit of 13.5 eV at the 95% confidence level. This result is not consistent with the long-standing ITEP result of 26(5) eV within a ''model-independent'' range of 17 to 40 eV. It now appears that the electron neutrino is not sufficiently massive to close the universe by itself. 38 refs., 1 figs., 2 tabs

  2. Results from PLUTO

    International Nuclear Information System (INIS)

    Results on the reaction e+ e- → μ+ μ- are presented. The data were taken with the PLUTO detector at the c.m. energy of 34.7 GeV. In the integrated luminosity of 44000 nb-1 taken, a forward backward asymmetry of -(12.0 + or - 3.2)% is observed for abs. value costheta <1 which is in agreement with the standard model

  3. Results from AMANDA

    OpenAIRE

    Hill, Gary C.; collaboration, for the AMANDA

    2001-01-01

    The AMANDA (Antarctic Muon And Neutrino Detector Array) detector, located at the South Pole station, Antarctica, was recently expanded with the addition of six new strings, completing the phase referred to as AMANDA-II. This detector has been calibrated and in operation since January 2000. The first data analyses are currently underway. In this report we present an update on the results from the AMANDA-B10 detector, which operated during the austral winter 1997.

  4. Recent results from LEP

    Indian Academy of Sciences (India)

    A Gurtu

    2000-04-01

    Recent results from the LEP collider at CERN are presented: on the identification of +- → +- and the determination of the mass and width and limits on its anomalous couplings; the search for the Standard Model and non-minimal Higgs; search for SUSY and other new particles. Fits to all electroweak data leading to predictions of the Higgs mass within the Standard Model are presented.

  5. Overview of ATLAS results

    CERN Document Server

    Grabowska-Bold, Iwona; The ATLAS collaboration

    2016-01-01

    The ATLAS experiment at the Large Hadron Collider has undertaken a broad physics program to probe and characterize the hot nuclear matter created in relativistic lead-lead collisions. This talk presents recent results based on Run 2 data on production of jet, electroweak bosons and quarkonium, electromagnetic processes in ultra-peripheral collisions, and bulk particle collectivity from PbPb, pPb and pp collisions.

  6. Recent BABAR Results

    CERN Document Server

    Eigen, Gerald

    2015-01-01

    We present herein the most recent BABAR results on direct CP asymmetry measurements in B -> Xs gamma, on partial branching fraction and CP asymmetry measurements in B -> Xs l+l-, on a search for B -> pi/eta l+l- decays, on a search for lepton number violation in B -> X-l+l'+ modes and a study of B-> omega omega and B-> omega phi decays.

  7. Overview of HERMES results

    OpenAIRE

    Van Hulse Charlotte

    2016-01-01

    The HERMES experiment has collected a wealth of deep-inelastic scattering data using the 27.6 GeV polarized lepton beam at HERA and various pure gas targets, both unpolarized and polarized. This allowed for a series of diverse and unique measurements. Among them are measurements that provide information on the threedimensional structure of the nucleon, both in momentum space and in position space. Results of measurements of exclusive ω production on an unpolarized and transversely polarized n...

  8. Recent QCD Results

    CERN Document Server

    Lincoln, Don

    2009-01-01

    The study of the inelastic scattering of hadrons has progressed in the last decade. With the availability of high-statistics data sets from HERA and the Tevatron, our understanding of high energy and high jet multiplicity events has become rather precise. In this Proceedings, I present an overview of recent jet-only results, as well as measurements of events which combine both jets and a W or Z boson.

  9. Explaining embodied cognition results.

    Science.gov (United States)

    Lakoff, George

    2012-10-01

    From the late 1950s until 1975, cognition was understood mainly as disembodied symbol manipulation in cognitive psychology, linguistics, artificial intelligence, and the nascent field of Cognitive Science. The idea of embodied cognition entered the field of Cognitive Linguistics at its beginning in 1975. Since then, cognitive linguists, working with neuroscientists, computer scientists, and experimental psychologists, have been developing a neural theory of thought and language (NTTL). Central to NTTL are the following ideas: (a) we think with our brains, that is, thought is physical and is carried out by functional neural circuitry; (b) what makes thought meaningful are the ways those neural circuits are connected to the body and characterize embodied experience; (c) so-called abstract ideas are embodied in this way as well, as is language. Experimental results in embodied cognition are seen not only as confirming NTTL but also explained via NTTL, mostly via the neural theory of conceptual metaphor. Left behind more than three decades ago is the old idea that cognition uses the abstract manipulation of disembodied symbols that are meaningless in themselves but that somehow constitute internal "representations of external reality" without serious mediation by the body and brain. This article uniquely explains the connections between embodied cognition results since that time and results from cognitive linguistics, experimental psychology, computational modeling, and neuroscience.

  10. GIRAFFE test results summary

    Energy Technology Data Exchange (ETDEWEB)

    Yokobori, S.; Arai, K.; Oikawa, H. [Toshiba Corporation, Kawasaki (Japan)

    1996-03-01

    A passive system can provide engineered safety features enhancing safety system reliability and plant simplicity. Toshiba has conducted the test Program to demonstrate the feasibility of the SBWR passive safety system using a full-height, integral system test facility GIRAFFE. The test facility GIRAFFE models the SBWR in full height to correctly present the gravity driving head forces with a 1/400 volume scale. The GIRAFFE test Program includes the certification tests of the passive containment cooling system (PCCS) to remove the post-accident decay heat and the gravity driven cooling system (GDCS) to replenish the reactor coolant inventory during a LOCA. The test results have confirmed the PCCS and GDCS design and in addition, have demonstrated the operation of the pCCS with the presence of a lighter-than-steam noncondensable as well as with the presence of a heavier-than-steam, noncondensable. The GIRAFFE test Program has also provided the database to qualify a best estimate thermal-hydraulic computer code TRAC. The post test analysis results have shown that TRAC can accurately predict the PCCS heat removal Performance and the containment pressure response to a LOCA. This paper summarizes the GIRAFFE test results to investigate post-LOCA PCCS heat removal performance and post-test analysis using TRAC.

  11. Recent CMS Results

    CERN Document Server

    Dorigo, Tommaso

    2012-01-01

    The CMS experiment obtained a large number of groundbreaking results from the analysis of 7- and 8-TeV proton-proton collisions produced so far by the Large Hadron Collider at CERN. In this brief summary only a sample of those results will be discussed. A new particle with mass m(H) = 125.3 +- 0.4(stat.) +- 0.5(syst.) GeV and characteristics compatible with those expected for a standard model Higgs boson has been observed in its decays to photon pairs, WW pairs, and ZZ pairs. Searches for the rare decays B_d -> mu mu and B_s -> mu mu have allowed to set limits on the branching fractions which are close to standard model predictions, strongly constraining new physics models. The top quark has been studied with great detail, obtaining among other results the world's best measurement of its mass as m(top) = 173.49 +- 0.43(stat. + JES) +- 0.98(syst.) GeV. New physics models have been strongly constrained with the available data.

  12. Pressure locking test results

    Energy Technology Data Exchange (ETDEWEB)

    DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D. [Idaho National Engineering Lab., Idaho Falls, ID (United States)] [and others

    1996-12-01

    The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.{close_quotes} Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; the authors will publish the results of their thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions.

  13. Scientific results report 1980

    International Nuclear Information System (INIS)

    The report describes in concise form the research tasks and results of the work groups pulsed irradiation, reaction kinematics and insulators and plastics in the field of 'radiation chemistry' of the Hahn-Meitner Institute, Berlin. The main topic of investigation was the kinetics and dynamics of fast chemical processes, the setting-up of chemical reaction mechanisms and research of chemical physical properties of highly reactive species (radicals, ions, electrons). A list of publications and lectures as well as teaching contributions of the institute's scientists, diploma and doctor theses performed in the institute and guest lectures held there is also given. (RB)

  14. Latest LHCb results

    Directory of Open Access Journals (Sweden)

    Martinelli Maurizio

    2014-01-01

    Full Text Available The LHCb experiment is one of the major research projects at the Large Hadron Collider. Its acceptance and instrumentation is optimised to perform high-precision studies of flavour physics and particle production in a unique kinematic range at unprecedented collision energies. Using large data samples accumulated in the years 2010-2012, the LHCb collaboration has conducted a series of measurements providing a sensitive test of the Standard Model and strengthening our knowledge of flavour physics, QCD and electroweak processes. The status of the experiment and some of its recent results are presented here.

  15. Recent Results from SELEX

    CERN Document Server

    Russ, J

    2001-01-01

    The SELEX experiment (E781) is 3-stage magnetic spectrometer for the study of charm hadroproduction at large xF using 600 Gev Sigma-, pi- and p beams. New precise measurements of the Lambda_c, D0, and Ds lifetimes are presented. We also report results on Lambda_c and Ds production by Sigma-, pi- and p beams at xF>0.2. The data agree with expectations from color-drag models to explain charm particle/antiparticle production asymmetries.

  16. Latest LHCb results

    Science.gov (United States)

    Martinelli, Maurizio

    2014-11-01

    The LHCb experiment is one of the major research projects at the Large Hadron Collider. Its acceptance and instrumentation is optimised to perform high-precision studies of flavour physics and particle production in a unique kinematic range at unprecedented collision energies. Using large data samples accumulated in the years 2010-2012, the LHCb collaboration has conducted a series of measurements providing a sensitive test of the Standard Model and strengthening our knowledge of flavour physics, QCD and electroweak processes. The status of the experiment and some of its recent results are presented here.

  17. Results from AMANDA

    CERN Document Server

    Wiebusch, C; Bai, X; Barwick, S W; Becka, T; Becker, K H; Bertrand, D; Bernadini, E; Binon, Freddy G; Biron, A; Boser, S; Botner, O; Bouchta, A; Bouhali, O; Burgess, T; Carius, S; Castermans, T; Chen, A; Chirkin, D; Conrad, J; Cooley, J; Cowen, D F; Davour, A; De Clercq, C; De Young, T R; Desiati, P; Dewulf, J P; Doksus, P; Ekstrom, P; Feser, T; Gaisser, T K; Gaug, M; Gerhardt, L; Goldschmidt, A; Hallgren, A; Halzen, F; Hanson, K; Hardtke, R; Hauschildt, T; Hellwig, M; Herquet, P; Hill, G C; Hulth, P O; Hundertmark, S; Jacobsen, J; Karle, A; Koci, B; Köpke, L; Kowalski, M; Kühn, K; Lamoureux, J I; Leich, H; Leuthold, M J; Lindahl, P; Liubarsky, I; Madsen, J; Marciniewski, P; Matis, H S; McParland, C P; Minaeva, Y; Minocinovic, P; Mock, P C; Morse, R; Nahnhauer, R; Neunhoffer, T; Niessen, P; Nygren, D R; Ögelman, H B; Olbrechts, P; Pérez de los Heros, C; Pohl, A C; Price, P B; Przybylski, G T; Rawlins, K; Resconi, E; Rhode, W; Ribordy, M; Richter, S; Rodríguez-Martino, J; Ross, D; Sander, H G; Schmidt, T; Schneider, D; Schwarz, R; Silvestri, A; Solarz, M; Spiczak, G M; Spiering, C; Steele, D; Steffen, P; Stokstad, R G; Sudhoff, P; Sulanke, K H; Taboada, I; Thollander, L; Tilav, S; Walck, C; Weinheimer, C; Wiebusch, C; Wiedemann, C; Wischnewski, R; Wissing, H; Woschnagg, K; Yodh, G B; Young, S

    2002-01-01

    The Antarctic Muon and Neutrino Detector Array (AMANDA) is a high- energy neutrino telescope operating at the geographic South Pole. It is a lattice of photomultiplier tubes buried deep in the polar ice. The primary goal of this detector is to discover astrophysical sources of high energy neutrinos. We describe the detector methods of operation and present results from the AMANDA-B10 prototype. We demonstrate the improved sensitivity of the current AMANDA-II detector. We conclude with an outlook to the envisioned sensitivity of the future IceCube detector. (37 refs).

  18. Recent BABAR Results

    Energy Technology Data Exchange (ETDEWEB)

    Eigen, Gerald [University of Bergen, Bergen (Norway). Dept. of Physics

    2015-04-29

    We present herein the most recent BABAR results on direct CP asymmetry measurements in B → Xsγ, on partial branching fraction and CP asymmetry measurements in B → Xs+-, on a search for B → π/ηℓ+- decays, on a search for lepton number violation in B+ → X-+ℓ'+ modes and a study of B0 →ωω and B0 → ωφ decays.

  19. Latest results from PAMELA

    Energy Technology Data Exchange (ETDEWEB)

    Papini, P. [INFN, Sezione di Firenze, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); Adriani, O. [INFN, Sezione di Firenze, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); University of Florence, Department of Physics, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); Barbarino, G.C. [University of Naples ' Federico II' , Department of Physics, Via Cintia, I-80126 Naples (Italy); INFN, Sezione di Napoli, Via Cintia, I-80126 Naples (Italy); Bazilevskaya, G.A. [Lebedev Physical Institute, Leninsky Prospekt 53, RU-119991 Moscow (Russian Federation); Bellotti, R. [University of Bari, Department of Physics, Via Amendola 173, I-70126 Bari (Italy); INFN, Sezione di Bari, Via Amendola 173, I-70126 Bari (Italy); Boezio, M. [INFN, Sezione di Trieste, Padriciano 99, I-34012 Trieste (Italy); Bogomolov, E.A. [Ioffe Physical Technical Institute, Polytekhnicheskaya 26, RU-194021 St. Petersburg (Russian Federation); Bonechi, L. [INFN, Sezione di Firenze, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); University of Florence, Department of Physics, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); Bongi, M. [INFN, Sezione di Firenze, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); Bonvicini, V. [INFN, Sezione di Trieste, Padriciano 99, I-34012 Trieste (Italy); Borisov, S. [INFN, Sezione di Roma ' Tor Vergata' , Via della Ricerca Scientifica 1, I-00133 Rome (Italy); Moscow Engineering and Physics Institute, Kashirskoe Shosse 31, RU-11540 Moscow (Russian Federation); Bottai, S. [INFN, Sezione di Firenze, Via Sansone 1, I-50019 Sesto Fiorentino, Florence (Italy); Bruno, A. [University of Bari, Department of Physics, Via Amendola 173, I-70126 Bari (Italy); INFN, Sezione di Bari, Via Amendola 173, I-70126 Bari (Italy); Cafagna, F. [INFN, Sezione di Bari, Via Amendola 173, I-70126 Bari (Italy); Campana, D. [INFN, Sezione di Napoli, Via Cintia, I-80126 Naples (Italy)

    2009-10-15

    The PAMELA experiment is a satellite-borne apparatus designed to study charged particles in the cosmic radiation, with a particular focus on antiparticles. The detector is housed on the Resurs-DK1 satellite and it is taking data since June 2006. The main parts of the apparatus are a magnetic spectrometer, which is equipped with a silicon-microstrip tracking system and which is used to measure the rigidity and the charge of particles, and a silicon/tungsten electromagnetic calorimeter which provides particle identification. The main results about the antiparticles component of cosmic rays obtained during the first 500 days of data taking are summarized here.

  20. Recent CDF results

    Energy Technology Data Exchange (ETDEWEB)

    Conway, J.S. [Rutgers--the State Univ., Piscataway, NJ (United States). Dept. of Physics and Astronomy; CDF Collaboration

    1996-07-01

    Preliminary results form the CDF detector, based on analysis of data collected in Run 1a and Run 1b at the Tevatron, totaling 110 pb{sup - 1} integrated luminosity, place new limits on the masses and couplings of new particles including charged Higgs bosons, supersymmetric gauge particles and quarks, and new vector bosons. One of the observed events, having an {ital e}{sup +}{ital e}{sup -} pair, two photons, and large missing energy would not occur with significant rate in the Standard Model, leading to speculation regarding its origin and the possible existence of related events.

  1. Recent results from ARGUS

    International Nuclear Information System (INIS)

    The ARGUS experiment, running at the DORIS II storage ring, has been collecting data on e+e- collisions near 10 GeV region since the end of 1982. The ARGUS detector, designed specifically for large acceptance and high resolution spectroscopy in the UPSILON resonances region, has produced a prolific amount of new results in recent months. Some of these are presented here. The subject matters include topics from charm and beauty spectroscopy and weak decays of charm mesons, beauty mesons and the tauon

  2. Overview of ALICE results

    CERN Document Server

    Gagliardi, M

    2014-01-01

    The ALICE experiment at the CERN LHC studies the hot and dense medium formed in ultra-relativistic heavy-ion collisions, and the transition to Quark Gluon Plasma. Several observables are used to characterise the medium. In this contribution we report on the main ALICE results on global properties, particle spectra, anisotropies, heavy flavour and quarkonium production, obtained in Pb-Pb collisions at √ s rmNN =2 . 76 TeV. Measurements performed in p-Pb and pp collisions are also part of the ALICE physics program: selected highlights from such measurements are discussed.

  3. First LHC Results

    CERN Document Server

    Horn, Claus; The ATLAS collaboration

    2010-01-01

    Since four month the Large Hadron Collider (LHC) is producing proton-proton collisions with a center of mass energy of 7 TeV offering the potential of directly producing dark matter particles in an energy range never reached before in accelerator-based particle physics. First the performance and first Standard Model measurements of the general purpose experiments CMS and ATLAS is presented. This talk then focuses on their potential to detect dark matter candidates. Results from ongoing physics analyzes are presented and expectations for possible future discoveries are discussed.

  4. Recent results from CMS

    CERN Document Server

    Dordevic, Milos

    2016-01-01

    The highlights of the most recent CMS results with 13 TeV data will be presented in this overview. The Standard Model precision measurements, including the top quark production, will be shown first. This will be followed by the presentation of Higgs boson studies with the early 13 TeV data. Then the focus will shift to searches for physics beyond the Standard Model, including the searches for several Supersymmetric scenarios, using different analysis techniques. The talk will conclude with searches for the exotic resonances, with an emphasis on studies of the high-mass diphoton production.

  5. New results from CLEO

    CERN Document Server

    Dubrovin, M S; Huang, G S; Lee, J; Miller, D H; Pavlunin, V; Rangarajan, R; Sanghi, B; Shibata, E I; Shipsey, I P J; Cronin-Hennessy, D; Park, C S; Park, W; Thayer, J B; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Boulahouache, C; Blusk, S; Dambasuren, E; Dorjkhaidav, O; Mountain, R; Muramatsu, H; Nandakumar, R; Skwarnicki, T; Stone, S; Wang, J C; Csorna, S E; Danko, I; Bonvicini, G; Cinabro, D; Dubrovin, M; McGee, S; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Sun, W M; Weinstein, A J; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G T; Vogel, H; Watkins, M E; Adam, N E; Alexander, J P; Berkelman, K; Boisvert, V; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Galik, R S; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Mistry, N B; Patterson, J R; Peterson, D; Pivarski, J; Richichi, S J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Thayer, J G; Urner, D; Wilksen, T; Warburton, A; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Potlia, V; Stöck, H; Yelton, J; Benslama, K; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Lowrey, N; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Besson, D; Anderson, S; Frolov, V V; Gong, D T; Kubota, Y; Li, S Z; Poling, R A; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z V; Seth, K K; Tomaradze, A G; Zweber, P; Ahmed, S; Alam, M S; Ernst, J; Jian, L; Saleem, M; Wappler, F; Arms, K; Eckhart, E; Gan, K K; Gwon, C; Honscheid, K; Kagan, H; Kass, R; Pedlar, T K; Von Törne, E; Severini, H; Skubic, P L; Dytman, S A; Müller, J A; Nam, S; Savinov, V

    2005-01-01

    We present recent results from the CLEO Collaboration. The data used were collected from 1995 untill now at the Cornell Electron-positron Storage Ring (CESR). Measurements of the leptonic branching fractions for $\\psi(2S) \\to e^+ e^-, \\mu^+ \\mu^-$ and $\\Upsilon(1,2,3S) \\to \\mu^+ \\mu^-$, search for $D^0-\\bar{D^0}$ mixing using time dependent Dalitz plot analyses of the decay $D^0 \\to K^0_S\\pi^+\\pi^-$, and search for the process $e^+e^- \\to \\Lambda_b \\bar{\\Lambda_b}$ near threshold are discussed.

  6. First result from Qweak

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, David S. [William and Mary College, JLAB

    2014-06-01

    Initial results are presented from the recently-completed Q{sub weak} experiment at Jefferson Lab. The goal is a precise measurement of the proton's weak charge Q{sub w}{sup p}, to yield a test of the standard model and to search for evidence of new physics. The weak charge is extracted from the parity-violating asymmetry in elastic {rvec e}p scattering at low momentum transfer, Q{sup 2} = 0.025 GeV{sup 2}. A 180 {micro} A longitudinally-polarized 1.16 GeV electron beam was scattered from a 35 cm long liquid hydrogen at small angles, 6 {degrees} < {theta} < 12 {degrees} Scattered electrons were analyzed in a toroidal magnetic field and detected using an array of eight Cerenkov detectors arranged symmetrically about the beam axis. The initial result, from 4% of the complete data set, is Q{sub W}{sup p} = 0.064 ± 0.012, in excellent agreement with the standard model expectation. Full analysis of the data is expected to yield a value for the weak charge to about 5% precision.

  7. Organic Separation Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Russell, Renee L.; Rinehart, Donald E.; Peterson, Reid A.

    2014-09-22

    Separable organics have been defined as “those organic compounds of very limited solubility in the bulk waste and that can form a separate liquid phase or layer” (Smalley and Nguyen 2013), and result from three main solvent extraction processes: U Plant Uranium Recovery Process, B Plant Waste Fractionation Process, and Plutonium Uranium Extraction (PUREX) Process. The primary organic solvents associated with tank solids are TBP, D2EHPA, and NPH. There is concern that, while this organic material is bound to the sludge particles as it is stored in the tanks, waste feed delivery activities, specifically transfer pump and mixer pump operations, could cause the organics to form a separated layer in the tank farms feed tank. Therefore, Washington River Protection Solutions (WRPS) is experimentally evaluating the potential of organic solvents separating from the tank solids (sludge) during waste feed delivery activities, specifically the waste mixing and transfer processes. Given the Hanford Tank Waste Treatment and Immobilization Plant (WTP) waste acceptance criteria per the Waste Feed Acceptance Criteria document (24590-WTP-RPT-MGT-11-014) that there is to be “no visible layer” of separable organics in the waste feed, this would result in the batch being unacceptable to transfer to WTP. This study is of particular importance to WRPS because of these WTP requirements.

  8. Latest Double Chooz results

    Science.gov (United States)

    Lasserre, Thierry; Double Chooz Collaboration

    2016-05-01

    I report the latest results from the Double Chooz experiment on the θ13 neutrino mixing angle. Two detectors are located at distances of 400 m and 1050 m from the reactor cores of the Chooz nuclear power station (France) to measure the disappearance of electron antineutrinos. The far detector has been taking data since 2011, accumulating a live time of 467.90 days (66.5 GW-ton-year). In this article we focus on the latest measurement using neutrino-induced neutron capture on hydrogen. A new analysis improved the signal efficiency and reduced the backgrounds and systematic uncertainties, leading to sin2 2θ 13 = 0.095+0.039 -0.038. When combined with the Gadolinium-based analysis this leads to sin2 2θ13 = 0.088+0.33 -0.033. The distortion from the prediction above a visible energy of 4 MeV is confirmed. The near detector started data taking in 2014 and first results shall be reported in 2016.

  9. Unfavourable results in pollicisation

    Directory of Open Access Journals (Sweden)

    Mukund R Thatte

    2013-01-01

    Full Text Available Pollicisation of the index finger is perhaps one of the most complex and most rewarding operations in hand and plastic surgery. It however has a steep learning curve and demands very high skill levels and experience. There are multiple pitfalls and each can result in an unfavourable result. In essence we need to: Shorten the Index, recreate the carpo metacarpal joint from the metacarpo phalangeal (MP joint, rotate the digit by about 120° for pulp to pulp pinch, palmarly abduct by 40-50° to get a new first web gap, Shorten and readjust the tension of the extensors, re attach the intrinsics to form a thenar eminence capable of positioning the new thumb in various functional positions and finally close the flaps forming a new skin envelope. The author has performed over 75 pollicisations personally and has personal experience of some of the issues raised there. The steps mentioned therefore are an algorithm for helping the uninitiated into these choppy waters.

  10. Archeomagnetic Results From Spain

    Science.gov (United States)

    Chauvin, A.; Gomez-Paccard, M.; Lanos, P.; Osete, M.; McIntosh, G.; Thiriot, J.

    2007-05-01

    A first secular variation (SV) curve for the Iberian Peninsula was computed by hierarchical Bayesian method using a total of 134 archaeomagnetic directions with ages ranging from 775 BC to 1959 A.D. A general agreement is observed between the Iberian curve and the French and German SV curves, excepted between the 11th and 14th centuries. The analysis of these three reference curves indicates that SV in western Europe is characterized by three major directional changes at 125, 200, and 1350 A.D. It is suggested that these cusps are regional features of the geomagnetic field. Archeointensity studies were also conducted on 24 Spanish archeomagnetic sites (220 AD to 1959 AD). Intensity data were obtained using the original Thellier method with anisotropy and cooling rates corrections. Our new 24 data, together with 62 previously published results, were used to recover, by Bayesian modelling, the geomagnetic field intensity evolution over the past two millennia for western Europe. Our results indicate that the geomagnetic intensity remains more or less constant between the 1st and 4th centuries, and between the 13th and 15th centuries, whereas an important decrease occurs during the last 5 centuries. The evolution of the Earth's magnetic field intensity during High Middle Ages remains uncertain. The available geomagnetic global models predict reasonably well our data.

  11. Double Chooz: Latest results

    CERN Document Server

    Crespo-Anadón, J I

    2014-01-01

    The latest results from the Double Chooz experiment on the neutrino mixing angle $\\theta_{13}$ are presented. A detector located at an average distance of 1050 m from the two reactor cores of the Chooz nuclear power plant has accumulated a live time of 467.90 days, corresponding to an exposure of 66.5 GW-ton-year (reactor power $\\times$ detector mass $\\times$ live time). A revised analysis has boosted the signal efficiency and reduced the backgrounds and systematic uncertainties compared to previous publications, paving the way for the two detector phase. The measured $\\sin^2 2\\theta_{13} = 0.090^{+0.032}_{-0.029}$ is extracted from a fit to the energy spectrum. A deviation from the prediction above a visible energy of 4 MeV is found, being consistent with an unaccounted reactor flux effect, which does not affect the $\\theta_{13}$ result. A consistent value of $\\theta_{13}$ is measured in a rate-only fit to the number of observed candidates as a function of the reactor power, confirming the robustness of the ...

  12. Recent results from CMS

    CERN Document Server

    CERN. Geneva

    2016-01-01

    With the increase in center-of-mass energy, a new energy frontier has been opened by the Large Hadron Collider. More than 25 fb^-1 of proton-proton collisions at sqrt(s)=13 TeV have been delivered to both ATLAS and CMS experiments during 2016. This enormous dataset can be used to test the Standard Model in a complete new regime with tremendous precision and it has the potential to unveil new physics or set strong bounds on it. In this talk some of the most recent results made public by the CMS Collaboration will be presented. The focus will mainly be on searches for physics beyond the Standard Model, with particular emphasis on searches for dark matter candidates.

  13. VRAC: Simulation Results #1

    CERN Document Server

    Huc, Florian

    2009-01-01

    In order to make full use of geographic routing techniques developed for large scale networks, nodes must be localized. However, localization and virtual localization techniques in sensor networks are dependent either on expensive and sometimes unavailable hardware (e.g. GPS) or on sophisticated localization calculus (e.g. triangulation) which are both error-prone and with a costly overhead. Instead of localizing nodes in a traditional 2-dimensional space, we use directly the raw distance to a set of anchors to route messages in a multi-dimensional space. This should enable us to use any geographic routing protocol in a robust and efficient manner in a very large range of scenarios. We test this technique for two different geographic routing algorithms, namely GRIC and ROAM. The simulation results show that using the raw coordinates does not decrease their efficiency.

  14. Recent Results from Phobos

    Science.gov (United States)

    García, Edmundo; Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Busza, W.; Carroll, A.; Chai, Z.; Decowski, M. P.; García, E.; Gburek, T.; George, N.; Gulbrandsen, K.; Halliwell, C.; Hamblen, J.; Hauer, M.; Henderson, C.; Hofman, D. J.; Hollis, R. S.; Hołyński, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Khan, N.; Kulinich, P.; Kuo, C. M.; Lin, W. T.; Manly, S.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Reed, C.; Roland, C.; Roland, G.; Sagerer, J.; Seals, H.; Sedykh, I.; Smith, C. E.; Stankiewicz, M. A.; Steinberg, P.; Stephans, G. S. F.; Sukhanov, A.; Tonjes, M. B.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Vaurynovich, S. S.; Verdier, R.; Veres, G. I.; Wenger, E.; Wolfs, F. L. H.; Wosiek, B.; Woźniak, K.; Wysłouch, B.

    2007-02-01

    The PHOBOS detector is one of four heavy ion experiments at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. In this paper we will review some of the results of PHOBOS from the data collected in p+p, d+Au and Au+Au collisions at nucleon-nucleon center-of-mass energies up to 200 GeV. Evidence is found of the formation of a very high energy density and highly interactive system, which can not be described in terms of hadrons, and has a relatively low baryon density. There is evidence that the system formed is thermalized to a certain degree. Scaling with the number of participants and extended longitudinal scaling behavior are also observed in distributions of produced charged particles.

  15. Recent results from LHCf

    Directory of Open Access Journals (Sweden)

    Menjo H.

    2015-01-01

    Full Text Available The LHCf experiment is one of the LHC forward experiments. The aim of LHCf is to provide critical calibration data of hadronic intraction models used in air shower simulations. The LHCf has completed the operations for p-p collisions with a collision energy of √s = 0.9 and 7 TeV p-p in 2010 and for p-Pb collisions with a collision energy per nucleon of √sNN = 5.02. The recent LHCf result of forward neutron energy spectra at 7 TeV p-p collision and forward π0 spectra at p-Pb collisions are presented in this paper.

  16. EIGER characterization results

    Energy Technology Data Exchange (ETDEWEB)

    Dinapoli, Roberto, E-mail: roberto.dinapoli@psi.ch [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Bergamaschi, Anna; Greiffenberg, Dominic; Henrich, Beat; Horisberger, Roland; Johnson, Ian; Mozzanica, Aldo [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Radicci, Valeria [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); ESRF, 6 Rue Horowitz, 38043 Grenoble (France); Schmitt, Bernd; Shi, Xintian [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Tinti, Gemma [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); ESRF, 6 Rue Horowitz, 38043 Grenoble (France)

    2013-12-11

    Characterization and performance measurements have been done on several EIGER detector systems, produced with chips coming from two different lots, both with a lab X-ray source and at the Swiss Light Source (SLS). Results on the detector calibration, electronic noise, threshold dispersion, minimum achievable energy threshold, maximum detectable incoming photon flux and maximum frame rate are presented. An EIGER module is constructed from a ∼4×8cm{sup 2} monolithic silicon sensor bump-bonded to 2 ×4 readout chips and contains 0.5 Mpixel. The first EIGER 500 K systems have been produced and images taken with these detectors are shown. Modules can be tiled together to form large area detectors; both a 9 Mpixel and a 16 Mpixel systems are at present under development for the coherent small angle X-ray scattering and protein crystallography beamlines of the SLS.

  17. EIGER characterization results

    Science.gov (United States)

    Dinapoli, Roberto; Bergamaschi, Anna; Greiffenberg, Dominic; Henrich, Beat; Horisberger, Roland; Johnson, Ian; Mozzanica, Aldo; Radicci, Valeria; Schmitt, Bernd; Shi, Xintian; Tinti, Gemma

    2013-12-01

    Characterization and performance measurements have been done on several EIGER detector systems, produced with chips coming from two different lots, both with a lab X-ray source and at the Swiss Light Source (SLS). Results on the detector calibration, electronic noise, threshold dispersion, minimum achievable energy threshold, maximum detectable incoming photon flux and maximum frame rate are presented. An EIGER module is constructed from a ∼4×8 cm2 monolithic silicon sensor bump-bonded to 2 ×4 readout chips and contains 0.5 Mpixel. The first EIGER 500 K systems have been produced and images taken with these detectors are shown. Modules can be tiled together to form large area detectors; both a 9 Mpixel and a 16 Mpixel systems are at present under development for the coherent small angle X-ray scattering and protein crystallography beamlines of the SLS.

  18. New results in percolation

    International Nuclear Information System (INIS)

    In this reprint some new results in percolation are reported. As a basic model the two-dimensional system, consisting of the phases with different conductivities, is considered. The phases are placed in a random way and in the double periodic structure also. For two-phase case it is shown that effective conductivity essentially depends on the microgeometry of the medium and the generalization of the Dykhne formula for the parallelogram unit cell is obtained. The percolation under quantum Hall effect conditions is studied by the general approach, using the symmetry of the system. The features of current percolation in QHE regime are established, and the effective characteristics and the local current distributions are found. For the problem of nonlinear percolation the new duality relations for critical exponents, described effective nonlinear current- voltage characteristics, are found. These duality relations are checked by the numerical simulations. (author)

  19. Recent results from ANTARES

    Directory of Open Access Journals (Sweden)

    Trovato Agata

    2015-01-01

    Full Text Available Operating 40 km off the coast of France since 2007, the ANTARES detector is the largest deep-sea neutrino telescope in the Northern Hemisphere with an instrumented volume of more than 0.01 cubic kilometers. It consists of an array of 885 photomultipliers detecting the Cherenkov light induced by charged leptons produced by neutrino interactions in and around the detector. The primary goal of ANTARES is to search for astrophysical neutrinos in the TeV–PeV range. This comprises generic searches for any diffuse cosmic neutrino flux as well as more specific searches for astrophysical galactic and extragalactic sources. The search program also includes multi-messenger analyses based on time and/or space coincidences with other cosmic probes. The ANTARES observatory is sensitive to a wide-range of other phenomena, from atmospheric neutrino oscillations to dark matter annihilation. In this contribution, recent results from the ANTARES neutrino telescope will be presented.

  20. Overview of HERMES results

    Science.gov (United States)

    Van Hulse, Charlotte

    2016-03-01

    The HERMES experiment has collected a wealth of deep-inelastic scattering data using the 27.6 GeV polarized lepton beam at HERA and various pure gas targets, both unpolarized and polarized. This allowed for a series of diverse and unique measurements. Among them are measurements that provide information on the threedimensional structure of the nucleon, both in momentum space and in position space. Results of measurements of exclusive ω production on an unpolarized and transversely polarized nucleon target, sensitive to the distribution in transverse-position and longitudinalmomentum space, are discussed as well as the three-dimensional extraction of azimuthal asymmetries measured in semi-inclusive deep-inelastic scattering, sensitive to twist-2 and twist-3 distributions in three-dimensional momentum space.

  1. Overview of HERMES results

    Directory of Open Access Journals (Sweden)

    Van Hulse Charlotte

    2016-01-01

    Full Text Available The HERMES experiment has collected a wealth of deep-inelastic scattering data using the 27.6 GeV polarized lepton beam at HERA and various pure gas targets, both unpolarized and polarized. This allowed for a series of diverse and unique measurements. Among them are measurements that provide information on the threedimensional structure of the nucleon, both in momentum space and in position space. Results of measurements of exclusive ω production on an unpolarized and transversely polarized nucleon target, sensitive to the distribution in transverse-position and longitudinalmomentum space, are discussed as well as the three-dimensional extraction of azimuthal asymmetries measured in semi-inclusive deep-inelastic scattering, sensitive to twist-2 and twist-3 distributions in three-dimensional momentum space.

  2. Results and discussion

    International Nuclear Information System (INIS)

    The author deals with the experimental study of sorption, desorption and vertical migration of radionuclides in Sr-85 and Cs-137 in selected soil samples from around of NPP Bohunice and NPP Mochovce and other localities of the Slovakia. The influence of different materials [concurrent ions (K+, Ca2+, NH4+, pH), organic matter (peat) and zeolite, humidity] on kinetic of sorption and desorption of strontium and cesium as well as distribution coefficient (KD) and transfer coefficients in followed samples of soils were followed. Obtained adsorption isotherm are presented and discussed. Using the Tessiere's sequential extraction analysis a gross variability in binding of radionuclides on soils was found. The obtained results were processed with the correlation analysis and the compartment model

  3. Areva - 2011 Annual results

    International Nuclear Information System (INIS)

    Areva's backlog established at 45.6 billion euros at the end of 2011, significantly increasing at the end of a year marked by the Fukushima accident, confirms the commercial dynamism of the group alongside its customers and reinforces the visibility on its future business level. In a difficult context, the slight decline in revenue in 2011 demonstrates the robustness of Areva's integrated model, resting mainly on recurring business generated in relation to Areva's customers' nuclear installed base, and benefiting from the development of Areva's renewable energies operations. Free operating cash flow before tax, although down over the whole year in 2011, improved in the second half, showing the first effects of Areva's stronger focus on cash generation and debt management. After the success of Areva's bond issue in September 2011, the Group's liquidity remains high at the end of 2011. The Areva teams are now dedicating all of their efforts to the deployment of the 'Action 2016' strategic action plan, which had already yielded its first positive results at the end of 2011, with an improvement in the cost structure of Areva's operations, an increase in order intake, and the launch of several disposals of minority interests. Summary of the 2011 financial results: - Backlog: euro 45.6 bn, +3.1% vs. 2010, i.e +6.7% over 3 months; - Revenue: euro 8.872 bn, i.e -2.6% vs. 2010; - Operating income: - euro 1.923 bn; - Net income attributable to equity owners of the parent: - euro 2.424 bn; - EBITDA: euro 1.068 bn ( euro 420 m excluding Siemens impact); - Free operating cash flow before tax: - euro 2.397 bn (- euro 1.366 bn excluding Siemens impacts), improvement over the second half; - Decrease in net debt of euro 124 m for the year; - Significant drop in general and administrative expenses, with a noticeable reduction between the first and the second half; - Launch of several disposals of minority interests

  4. Report on Results 2000

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This report discusses work being carried out in Norway to promote energy efficiency and the production of new renewable energy. An overall review of the quantifiable results of last year's activities at national level is available. It will serve to initiate an annual reporting tradition. The report represents a step towards an ongoing process for improved targeting and management of national efforts. During the course of the year 2000, NVE has evaluated and adjusted its activities and established a system involving indicators and reporting procedures. It is also important to take notice of the long-term work being undertaken to influence people's attitudes, even though this work is difficult to assess. NVE is investing in i.a. measures aimed at children and young people. Apart from directly influencing future energy users, this investment is also having an effect due to the children's encouragement of their parents to engage in more energy and environment-friendly behaviour. Published in 2000, the IEA report ''Trends in Norwegian Stationary Energy Use'' shows that total Norwegian energy consumption per GDP is not much higher than in other IEA countries, when adjusted for cold climate and industrial structure. However, Norwegians do stand out as intensive users of electricity. The IEA report shows a reduction of 10 TWh in energy usage when compared to the projected post 1990 figures. Energy efficiency activities have contributed towards this reduction. However, the potential for a more rational use of energy in Norway is still substantial and well documented. Based on experience most enterprises could save around 10% of energy used just by making changes to their operations, i.e. without major investments. Furthermore, the potential is growing because of massive technological developments in respect of energy usage, production and distribution. With this in mind, it is necessary to take full advantage of the extensive knowledge

  5. Simpler images, better results

    Science.gov (United States)

    Chance, Britton

    1999-03-01

    The very rapid development of optical technology has followed a pattern similar to that of nuclear magnetic resonance: first, spectroscopy and then imaging. The accomplishments in spectroscopy have been significant--among them, early detection of hematomas and quantitative oximetry (assuming that time and frequency domain instruments are used). Imaging has progressed somewhat later. The first images were obtained in Japan and USA a few years ago, particularly of parietal stimulation of the human brain. Since then, rapid applications to breast and limb, together with higher resolution of the brain now make NIR imaging of functional activation and tumor detection readily available, reliable and affordable devices. The lecture has to do with the applications of imaging to these three areas, particularly to prefrontal imaging of cognitive function, of breast tumor detection, and of localized muscle activation in exercise. The imaging resolution achievable in functional activation appears to be FWHM of 4 mm. The time required for an image is a few seconds or even much less. Breast image detection at 50 microsecond(s) ec/pixel results in images obtainable in a few seconds or shorter times (bandwidths of the kHz are available). Finally, imaging of the body organs is under study in this laboratory, particularly in the in utero fetus. It appears that the photon migration theory now leads to the development of a wide number of images for human subject tissue spectroscopy and imaging.

  6. Results from PLUTO

    International Nuclear Information System (INIS)

    Recent results obtained with the PLUTO detector at the e+e- storage ring PETRA are reviewed. The validity of QED has been successfully tested in five independent reactions at spacelike momentum transfers up to -850 GeV2 and timelike momentum transfers up to 1000 GeV2. We are performing a detailed study of hadron production through 2 γ interactions. In particular we have measured the total hadronic γγ cross section and have determined the radiative width of the f0 meson to be GAMMA (f → γγ) = (2.3 +- 0.5 +- 0.35) keV. The first indication for the production of large P(t) jets in 2γ interactions is presented. We find no evidence for a tt threshold in the rate of inclusive muons. Finally we give a lower limit (95% c.1.) of 13 GeV on the mass of a spin 0 electron expected from supersymmetry

  7. ALOS-2 initial results

    Science.gov (United States)

    Kankaku, Yukihiro; Suzuki, Shinichi; Shimada, Masanobu

    2015-10-01

    The Advanced Land Observing Satellite-2 (ALOS-2) was launched from Tanegashima Space Center by H-IIA rocket successfully on 24th May 2014. ALOS-2 carries the Phased Array type L-band Synthetic Aperture Radar-2 (PALSAR-2) as the state-of-the-art L-band SAR system which succeeds to PALSAR onboard ALOS. PALSAR-2 uses almost whole bandwidth allocated for L-band active sensor of Earth Exploration Satellites Service specified by the Radio Regulation in order to realize the high resolution observation, and also, it transmits more than 6 kW power for lower Noise Equivalent Sigma Zero using 180 TRMs driven by Gallium Nitride (GaN) amplifier which is the first use in space. Furthermore, because ALOS-2 carries the SAR system only, PALSAR-2 antenna can be mounted under the satellite body. It enables to observe right-/left-looking observation by satellite maneuvering. And the high accuracy orbit control to maintain the satellite within 500 m radius tube against the reference orbit enables high coherence for the InSAR processing. Using these new technologies, ALOS-2 has been operating to fulfill the mission requirements such as disaster monitoring and so on. This document introduces the initial result of ALOS-2 from the first year operation.

  8. Lower gastrointestinal endoscopies results

    Directory of Open Access Journals (Sweden)

    Ahmet Bozdağ

    2014-12-01

    Full Text Available Objectives: Endoscopic examinations have great potential in early diagnosis of colorectal adenomas and carcinomas with reducing to colorectal cancer incidence and mortality. We aimed to evaluate for diagnostic purposeful lower gastrointestinal endoscopic procedures in the second step state hospital retrospectively Methods: Between June 2010 and June 2013, we evaluated 278 patients with rectal bleeding, constipation and abdominal pain detected by lower gastrointestinal endoscopic procedures retrospectively. Results: The mean age of the patients was 54.8 ± 16.8 (15-90 year, respectively. 172 (61.9% of the patients were male and 106 (38.1% of the patients were female. 116 (41.7% of the patients was performed rectosigmoidoscopy and 162 (58.3% of the patients was performed colonoscopy. 51(18.3% of our patients were normal. 10 (3.6% of patients had colorectal cancer, 11(3.9% of patients had inflammatory bowel disease, 8 (2.9% of patients had parasitosis, 31(11.1% of patients had colorectal polyps, 12 (4.3% , in patients had diverticular disease, 2 (0.7% patients had rectal ulcer, 25 (9% patients had anal fissure and 159 (57.2% of the patients had hemorrhoidal disease. Conclusion: Lower gastrointestinal endoscopy is a method been the gold standard with a low complication rate and that can be easily applied in the evaluation to pathology of colorectal and anal canal. J Clin Exp Invest 2014; 5 (4: 580-582

  9. ESR teleradiology survey: results.

    Science.gov (United States)

    2016-08-01

    With recent developments of teleradiology technology and services, it has become necessary to better evaluate its extent and use among different countries in Europe. With this goal in mind, the ESR launched two specific surveys intended to gather the current state of adoption and implementation of teleradiology in clinical practice. A special focus on differentiating between insourcing teleradiology services among partners of the same organisation and outsourcing to external services was an essential part of the design of these surveys. The first survey was addressed to 44 national societies of different countries in Europe, while the second survey was intended for all practicing radiologist ESR members. While the results of these surveys reported here may provide a wealth of information to better understand the trends in adoption of teleradiology in Europe, they only represent a snapshot at a certain point in time. The rapid development of telecommunication tools as well as a fundamental change in practice and healthcare economics will certainly influence these observations in the upcoming years. These data, however, will provide objective and relevant parameters for supporting the efforts of experts and policy makers in promoting appropriate criteria and guidelines for adequate use of teleradiology in clinical practice. Main Messages • Understand concepts and challenges of teleradiology • Provide insight into current trends and solutions for teleradiology • Compare differences in teleradiolgy strategies between countries in Europe • Establish a reference on statistical data of usage of teleradiology in Europe. PMID:27188379

  10. Climax granite test results

    International Nuclear Information System (INIS)

    The Lawrence Livermore Laboratory (LLL), as part of the Nevada Nuclear Waste Storage Investigations (NNWSI) program, is carrying out in situ rock mechanics testing in the Climax granitic stock at the Nevada Test Site (NTS). This summary addresses only those field data taken to date that address thermomechanical modeling for a hard-rock repository. The results to be discussed include thermal measurements in a heater test that was conducted from October 1977 through July 1978, and stress and displacement measurements made during and after excavation of the canister storage drift for the Spent Fuel Test (SFT) in the Climax granite. Associated laboratory and field measurements are summarized. The rock temperature for a given applied heat load at a point in time and space can be adequately modeled with simple analytic calculations involving superposition and integration of numerous point source solutions. The input, for locations beyond about a meter from the source, can be a constant thermal conductivity and diffusivity. The value of thermal conductivity required to match the field data is as much as 25% different from laboratory-measured values. Therefore, unless we come to understand the mechanisms for this difference, a simple in situ test will be required to obtain a value for final repository design. Some sensitivity calculations have shown that the temperature field is about ten times more sensitive to conductivity than to diffusivity under the test conditions.The orthogonal array was designed to detect anisotropy. After considering all error sources, anisotropic efforts in the thermal field were less than 5 to 10%

  11. Areva: 2014 annual results

    International Nuclear Information System (INIS)

    The scale of the net loss for 2014 illustrates the twofold challenge confronting AREVA: continuing stagnation of the nuclear operations, lack of competitiveness and difficulties in managing the risks inherent in large projects. The group understands how serious this situation is. A comprehensive strategic review of operations was undertaken beginning in November 2014 and is being carried out without compromise. As a result, AREVA is now able to announce a solid transformation plan that sets a challenging but economically realistic course for its teams. First, AREVA will refocus on its core business: mastery of key nuclear processes essential to operators around the globe. This strategic redeployment will lead to the revision of certain goals, whether in the management of new reactor projects or in renewable energies. AREVA's objective is to achieve excellence as a high value-added supplier of products and services. Secondly, AREVA, whose resources had been marshaled to support a spurt of growth in nuclear power, must now adapt to new market realities and become competitive once again. The group's most urgent task is recovery and securing its future by immediately launching a far-reaching competitiveness plan founded on organizational simplification, quality of operations, and a completely revamped approach to managing risk in large projects. Last but not least, AREVA must ensure sustainable financing for its activities. A financing plan will be clarified before publication of the half-year financial statements. This document presents the key financial data of the group, its strategic road-map and its operating and financing plans

  12. Oncogenic BRAF(V600E Induces Clastogenesis and UVB Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Dennis A. Simpson

    2015-06-01

    Full Text Available The oncogenic BRAF(V600E mutation is common in melanomas as well as moles. The roles that this mutation plays in the early events in the development of melanoma are poorly understood. This study demonstrates that expression of BRAF(V600E is not only clastogenic, but synergizes for clastogenesis caused by exposure to ultraviolet radiation in the 300 to 320 nM (UVB range. Expression of BRAF(V600E was associated with induction of Chk1 pS280 and a reduction in chromatin remodeling factors BRG1 and BAF180. These alterations in the Chk1 signaling pathway and SWI/SNF chromatin remodeling pathway may contribute to the clastogenesis and UVB sensitivity. These results emphasize the importance of preventing sunburns in children with developing moles.

  13. Overview of MAST results

    Science.gov (United States)

    Chapman, I. T.; Adamek, J.; Akers, R. J.; Allan, S.; Appel, L.; Asunta, O.; Barnes, M.; Ben Ayed, N.; Bigelow, T.; Boeglin, W.; Bradley, J.; Brünner, J.; Cahyna, P.; Carr, M.; Caughman, J.; Cecconello, M.; Challis, C.; Chapman, S.; Chorley, J.; Colyer, G.; Conway, N.; Cooper, W. A.; Cox, M.; Crocker, N.; Crowley, B.; Cunningham, G.; Danilov, A.; Darrow, D.; Dendy, R.; Diallo, A.; Dickinson, D.; Diem, S.; Dorland, W.; Dudson, B.; Dunai, D.; Easy, L.; Elmore, S.; Field, A.; Fishpool, G.; Fox, M.; Fredrickson, E.; Freethy, S.; Garzotti, L.; Ghim, Y. C.; Gibson, K.; Graves, J.; Gurl, C.; Guttenfelder, W.; Ham, C.; Harrison, J.; Harting, D.; Havlickova, E.; Hawke, J.; Hawkes, N.; Hender, T.; Henderson, S.; Highcock, E.; Hillesheim, J.; Hnat, B.; Holgate, J.; Horacek, J.; Howard, J.; Huang, B.; Imada, K.; Jones, O.; Kaye, S.; Keeling, D.; Kirk, A.; Klimek, I.; Kocan, M.; Leggate, H.; Lilley, M.; Lipschultz, B.; Lisgo, S.; Liu, Y. Q.; Lloyd, B.; Lomanowski, B.; Lupelli, I.; Maddison, G.; Mailloux, J.; Martin, R.; McArdle, G.; McClements, K.; McMillan, B.; Meakins, A.; Meyer, H.; Michael, C.; Militello, F.; Milnes, J.; Morris, A. W.; Motojima, G.; Muir, D.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A.; O'Brien, M.; O'Gorman, T.; Ono, Y.; Oliver, H.; Pamela, S.; Pangione, L.; Parra, F.; Patel, A.; Peebles, W.; Peng, M.; Perez, R.; Pinches, S.; Piron, L.; Podesta, M.; Price, M.; Reinke, M.; Ren, Y.; Roach, C.; Robinson, J.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Schekochihin, A.; Sharapov, S.; Sharples, R.; Shevchenko, V.; Silburn, S.; Simpson, J.; Storrs, J.; Takase, Y.; Tanabe, H.; Tanaka, H.; Taylor, D.; Taylor, G.; Thomas, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M.; Valovic, M.; Vann, R.; Walkden, N.; Wilson, H.; Wyk, L. V.; Yamada, T.; Zoletnik, S.; MAST; MAST Upgrade Teams

    2015-10-01

    The Mega Ampère Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number nRMP = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating nRMP = 3 RMPs. nRMP = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with nRMP = 4 than nRMP = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with ‘classical’ fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved

  14. AREVA annual results 2009

    International Nuclear Information System (INIS)

    AREVA expanded its backlog and increased its revenues compared with 2008, on strong installed base business and dynamic major projects, fostering growth in operating income of 240 million euros. As announced previously, Areva is implementing a financing plan suited to its objectives of profitable growth. The plan was implemented successfully in 2009, including the conclusion of an agreement, under very satisfactory terms, to sell its Transmission and Distribution business for 4 billion euros, asset sales for more than 1.5 billion euros, and successful bond issues of 3 billion euros. The plan will continue in 2010 with a capital increase, the completion of asset disposals and cost reduction and continued operational performance improvement programs. Areva bolstered its Renewable Energies business segment by supplementing its offshore wind power and biomass businesses with the acquisition of Ausra, a California-based leader in concentrated solar power technology. Despite the sale of T and D, Areva is maintaining its financial performance outlook for 2012: 12% average annual revenue growth to 12 billion euros in 2012, double digit operating margin and substantially positive free operating cash flow. Annual results 2009: - For the group as a whole, including Transmission and Distribution: Backlog: euros 49.4 bn (+2.5%), Revenues: euros 14 bn (+6.4%), Operating income: euros 501 m (+20.1%); - Nuclear and Renewable Energies perimeter: Backlog: euros 43.3 bn (+1.8%), Strong revenue growth: +5.4% to euros 8.5 bn, Operating income before provision for the Finnish project in the first half of 2009: euros 647 m, Operating income: euros 97 m, for a euros 240 m increase from 2008; - Net income attributable to equity holders of the parent: euros 552 m, i.e. euros 15.59 per share; - Net debt: euros 6,193 m; - Pro-forma net debt, including net cash to be received from the sale of T and D in 2010: euros 3,022 m; - Dividend of euros 7.06 per share to be proposed during the Annual

  15. A mitogen-activated protein kinase of the corn leaf pathogen Cochliobolus heterostrophus is involved in conidiation, appressorium formation, and pathogenicity: diverse roles for mitogen-activated protein kinase homologs in foliar pathogens.

    Science.gov (United States)

    Lev, S; Sharon, A; Hadar, R; Ma, H; Horwitz, B A

    1999-11-01

    Fungal pathogens perceive and respond to molecules from the plant, triggering pathogenic development. Transduction of these signals may use heterotrimeric G proteins, and it is thought that protein phosphorylation cascades are also important. We have isolated a mitogen-activated protein kinase homolog from the corn pathogen Cochliobolus heterostrophus to test its role as a component of the transduction pathways. The new gene, CHK1, has a deduced amino acid sequence 90% identical to Pmk1 of the rice blast fungus Magnaporthe grisea and 59% identical to Fus3 of Saccharomyces cerevisiae. A series of chk1 deletion mutants has poorly developed aerial hyphae, autolysis, and no conidia. No pseudothecia are formed when a cross between two Deltachk1 mutants is attempted. The ability of Deltachk1 mutants to infect corn plants is reduced severely. The growth pattern of hyphae on a glass surface is strikingly altered from that of the wild type, forming coils or loops, but no appressoria. This set of phenotypes overlaps only partially with that of pmk1 mutants, the homologous gene of the rice blast fungus. In particular, sexual and asexual sporulation both require Chk1 function in Cochliobolus heterostrophus, in contrast to Pmk1, but perhaps more similar to yeast, where Fus3 transmits the mating signal. Chk1 is required for efficient colonization of leaf tissue, which can be compared with filamentous invasive growth of yeast, modulated through another closely related mitogen-activated protein kinase, Kss1. Ubiquitous signaling elements thus are used in diverse ways in different plant pathogens, perhaps the result of coevolution of the transducers and their targets. PMID:10557357

  16. Atrazine Triggers DNA Damage Response and Induces DNA Double-Strand Breaks in MCF-10A Cells.

    Science.gov (United States)

    Huang, Peixin; Yang, John; Ning, Jie; Wang, Michael; Song, Qisheng

    2015-06-24

    Atrazine, a pre-emergent herbicide in the chloro-s-triazine family, has been widely used in crop lands and often detected in agriculture watersheds, which is considered as a potential threat to human health. Although atrazine and its metabolites showed an elevated incidence of mammary tumors in female Sprague-Dawley (SD) rats, no molecular evidence was found relevant to its carcinogenesis in humans. This study aims to determine whether atrazine could induce the expression of DNA damage response-related proteins in normal human breast epithelial cells (MCF-10A) and to examine the cytotoxicity of atrazine at a molecular level. Our results indicate that a short-term exposure of MCF-10A to an environmentally-detectable concentration of atrazine (0.1 µg/mL) significantly increased the expression of tumor necrosis factor receptor-1 (TNFR1) and phosphorylated Rad17 in the cells. Atrazine treatment increased H2AX phosphorylation (γH2AX) and the formation of γH2AX foci in the nuclei of MCF-10A cells. Atrazine also sequentially elevated DNA damage checkpoint proteins of ATM- and RAD3-related (ATR), ATRIP and phospho-Chk1, suggesting that atrazine could induce DNA double-strand breaks and trigger the DNA damage response ATR-Chk1 pathway in MCF-10A cells. Further investigations are needed to determine whether atrazine-triggered DNA double-strand breaks and DNA damage response ATR-Chk1 pathway occur in vivo.

  17. Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe.

    Science.gov (United States)

    Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C

    2007-11-01

    As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage. PMID:17947424

  18. Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer.

    Science.gov (United States)

    Yang, Shih-Hung; Kuo, Ting-Chun; Wu, Hsu; Guo, Jhe-Cyuan; Hsu, Chiun; Hsu, Chih-Hung; Tien, Yu-Wen; Yeh, Kun-Huei; Cheng, Ann-Lii; Kuo, Sung-Hsin

    2016-08-28

    Pancreatic cancer is highly lethal. Current research that combines radiation with targeted therapy may dramatically improve prognosis. Cancerous cells are characterized by unstable genomes and activation of DNA repair pathways, which are indicated by increased phosphorylation of numerous factors, including H2AX, ATM, ATR, Chk1, Chk2, DNA-PKcs, Rad51, and Ku70/Ku80 heterodimers. Radiotherapy causes DNA damage. Cancer cells can be made more sensitive to the effects of radiation (radiosensitization) through inhibition of DNA repair pathways. The synergistic effects, of two or more combined non-lethal treatments, led to co-administration of chemotherapy and radiosensitization in BRCA-defective cells and patients, with promising results. ATM/Chk2 and ATR/Chk1 pathways are principal regulators of cell cycle arrest, following DNA double-strand or single-strand breaks. DNA double-stranded breaks activate DNA-dependent protein kinase, catalytic subunit (DNA-PKcs). It forms a holoenzyme with Ku70/Ku80 heterodimers, called DNA-PK, which catalyzes the joining of nonhomologous ends. This is the primary repair pathway utilized in human cells after exposure to ionizing radiation. Radiosensitization, induced by inhibitors of ATM, ATR, Chk1, Chk2, Wee1, PP2A, or DNA-PK, has been demonstrated in preclinical pancreatic cancer studies. Clinical trials are underway. Development of agents that inhibit DNA repair pathways to be clinically used in combination with radiotherapy is warranted for the treatment of pancreatic cancer. PMID:27621574

  19. Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders

    OpenAIRE

    Schaevitz, LS; Picker, JD; J. Rana; Kolodny, NH; Shane, B; Berger-Sweeney, JE; Coyle, JT

    2012-01-01

    Interactions between genetic and environmental risk factors underlie a number of neuropsychiatric disorders, including schizophrenia (SZ) and autism (AD). Due to the complexity and multitude of the genetic and environmental factors attributed to these disorders, recent research strategies focus on elucidating the common molecular pathways through which these multiple risk factors may function. In this study, we examine the combined effects of a haplo-insufficiency of glutamate carboxypeptidas...

  20. Endoglin haploinsufficiency attenuates radiation-induced deterioration of kidney function in mice

    NARCIS (Netherlands)

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.

    2013-01-01

    Background and Purpose: Endoglin is a transforming growth receptor beta (TGF-beta) co-receptor, which plays a crucial role in the development of late normal tissue damage. Mice with halved endoglin levels (Eng(+/-) mice) develop less inflammation, vascular damage and fibrosis after kidney irradiatio

  1. Haploinsufficiency of Def Activates p53-Dependent TGFβ Signalling and Causes Scar Formation after Partial Hepatectomy

    OpenAIRE

    Zhihui Zhu; Jun De Chen; Jing-Wei Xiong; Jinrong Peng

    2014-01-01

    The metazoan liver exhibits a remarkable capacity to regenerate lost liver mass without leaving a scar following partial hepatectomy (PH). Whilst previous studies have identified components of several different signaling pathways that are essential for activation of hepatocyte proliferation during liver regeneration, the mechanisms that enable such regeneration to occur without accompanying scar formation remain poorly understood. Here we use the adult zebrafish liver, which can regenerate wi...

  2. Atm-haploinsufficiency enhances susceptibility to carcinogen-induced mammary tumors.

    OpenAIRE

    Lu, Shu; Shen, Kate; Wang, Yaolin; Santner, Steven J.; Chen, Jie; Brooks, S. C.; Wang, Y. Alan

    2006-01-01

    Biomarkers of exposure & effect:: validationBiomarker: A-T carriersExposure/effect represented: DMBAStudy type (in vitro, animals, humans): Atm male miceMode of exposure (if in vivo) (acute, chronic, root of exposure): administration by oral gavageMethod of analysis: PCRDose-response: Nearly twice as many Atm heterozygotes developed mammary tumors (64.7%) as the wild-type mice (37.5%). RR for DMBA-induced mammary tumors is 1.7 for Atm heterozygotesAtm heterozygotes developed mammary tumors wi...

  3. Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients.

    Science.gov (United States)

    Lehalle, Daphné; Gordon, Christopher T; Oufadem, Myriam; Goudefroye, Géraldine; Boutaud, Lucile; Alessandri, Jean-Luc; Baena, Neus; Baujat, Geneviève; Baumann, Clarisse; Boute-Benejean, Odile; Caumes, Roseline; Decaestecker, Charles; Gaillard, Dominique; Goldenberg, Alice; Gonzales, Marie; Holder-Espinasse, Muriel; Jacquemont, Marie-Line; Lacombe, Didier; Manouvrier-Hanu, Sylvie; Marlin, Sandrine; Mathieu-Dramard, Michèle; Morin, Gilles; Pasquier, Laurent; Petit, Florence; Rio, Marlène; Smigiel, Robert; Thauvin-Robinet, Christel; Vasiljevic, Alexandre; Verloes, Alain; Malan, Valérie; Munnich, Arnold; de Pontual, Loïc; Vekemans, Michel; Lyonnet, Stanislas; Attié-Bitach, Tania; Amiel, Jeanne

    2014-04-01

    Mandibulofacial dysostosis, Guion-Almeida type (MFDGA) is a recently delineated multiple congenital anomalies/mental retardation syndrome characterized by the association of mandibulofacial dysostosis (MFD) with external ear malformations, hearing loss, cleft palate, choanal atresia, microcephaly, intellectual disability, oesophageal atresia (OA), congenital heart defects (CHDs), and radial ray defects. MFDGA emerges as a clinically recognizable entity, long underdiagnosed due to highly variable presentations. The main differential diagnoses are CHARGE and Feingold syndromes, oculoauriculovertebral spectrum, and other MFDs. EFTUD2, located on 17q21.31, encodes a component of the major spliceosome and is disease causing in MFDGA, due to heterozygous loss-of-function (LoF) mutations. Here, we describe a series of 36 cases of MFDGA, including 24 previously unreported cases, and we review the literature in order to delineate the clinical spectrum ascribed to EFTUD2 LoF. MFD, external ear anomalies, and intellectual deficiency occur at a higher frequency than microcephaly. We characterize the evolution of the facial gestalt at different ages and describe novel renal and cerebral malformations. The most frequent extracranial malformation in this series is OA, followed by CHDs and skeletal abnormalities. MFDGA is probably more frequent than other syndromic MFDs such as Nager or Miller syndromes. Although the wide spectrum of malformations complicates diagnosis, characteristic facial features provide a useful handle.

  4. Rad21-cohesin haploinsufficiency impedes DNA repair and enhances gastrointestinal radiosensitivity in mice

    NARCIS (Netherlands)

    H. Xu (Huiling); K. Balakrishnan (Kannan); J. Malaterre (Jordane); M. Beasley (Matthew); Y. Yan (Yuqian); J. Essers (Jeroen); E. Appeldoorn (Esther); J.M. Thomaszewski (Jonathan); M. Vazquez (Melisa); S. Verschoor (Sandra); M.F. Lavin (Martin); I. Bertonchello (Ivan); R.G. Ramsay (Robert); M.J. Mckay (Michael)

    2010-01-01

    textabstractApproximately half of cancer-affected patients receive radiotherapy (RT). The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation respo

  5. Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning disability

    NARCIS (Netherlands)

    Johansson, S.; Berland, S.; Gradek, G.A.; Bongers, E.; Leeuw, N. de; Pfundt, R.P.; Fannemel, M.; Rodningen, O.; Brendehaug, A.; Haukanes, B.I.; Hovland, R.; Helland, G.; Houge, G.

    2014-01-01

    MEIS2 is a homeodomain-containing transcription factor of the TALE superfamily that has been proven important for development. We confirm and extend a recent single clinical report stating that deletions in MEIS2 can cause cleft palate [Crowley et al. (2010); Am J Med Genet 152A:1326-1327]. Here we

  6. Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma

    NARCIS (Netherlands)

    Choorapoikayil, Suma; Kuiper, Raoul V.; de Bruin, Alain; den Hertog, Jeroen

    2012-01-01

    PTEN is an essential tumor suppressor that antagonizes Akt/PKB signaling. The zebrafish genome encodes two Pten genes, ptena and ptenb. Here, we report that zebrafish mutants that retain a single wild-type copy of ptena or ptenb (ptena(+/)-ptenb(-/-) or ptena(-/-)ptenb(+/-)) are viable and fertile.

  7. Variant haploinsufficiency and phenotypic non-penetrance in PRPF31-associated retinitis pigmentosa.

    Science.gov (United States)

    Rose, A M; Bhattacharya, S S

    2016-08-01

    Retinitis pigmentosa (RP) is a genetically heterogenous group of inherited disorders, characterized by death of the retinal photoreceptor cells, leading to progressive visual impairment. One form of RP is caused by mutations in the ubiquitously expressed splicing factor, PRPF31, this form being known as RP11. An intriguing feature of RP11 is the presence of non-penetrance, which has been observed in the majority of PRPF31 mutation-carrying families. In contrast to variable expressivity, which is highly pervasive, true non-penetrance is a very rare phenomenon in Mendelian disorders. In this article, the molecular mechanisms underlying phenotypic non-penetrance in RP11 are explored. It is an elegant example of how our understanding of monogenic disorders has evolved from studying only the disease gene, to considering a mutation on the genetic background of the individual - the logical evolution in this genomic era. PMID:26853529

  8. Aesthetic rhinoplasty: Avoiding unfavourable results

    Directory of Open Access Journals (Sweden)

    Kulwant S Bhangoo

    2013-01-01

    Full Text Available Rhinoplasty is one of the most challenging surgical procedures in plastic surgery. It is not surprising that a significant number of patients end up with unfavourable outcomes. Many of these unfavourable outcomes could be the result of poor judgment and wrong decision making. Most frequently, the unfavourable outcome is the result of errors in surgical technique. In this paper, unfavourable outcomes resulting from errors in surgical technique are discussed under the heading of each operative step. Poor placement of intra-nasal incision can result in internal valve obstruction. Bad columellar scars can result from errors during open rhinoplasty. Unfavourable results associated with skeletonisation are mentioned. Tip plasty, being the most difficult part of rhinoplasty, can result in lack of tip projection, asymmetry and deformities associated with placement of tip grafts. Over-resection of the lower lateral cartilages during tip plasty can also result in pinched nose, alar collapse causing external valve obstruction and other alar rim deformities. Humpectomy can result in open roof deformity, inverted V deformity and over-resection resulting in saddle nose. The so-called poly beak deformity is also a preventable unfavourable outcome when dealing with a large dorsal hump. Complications resulting from osteotomies include narrowing of nasal airway, open roof deformity, inverted V deformity and asymmetry of the bony wall resulting from incomplete or green stick fractures. Judicious use of grafts can be very rewarding. By the same token, grafts also carry with them the risk of complications. Allografts can result in recurrent infection, atrophy of the overlying skin and extrusion resulting in crippling deformities. Autografts are recommended by the author. Unfavourable results from autografts include displacement of graft, visibility of the graft edges, asymmetry, warping, and resorption.

  9. Testbeam Results of Endcap RPC's

    CERN Document Server

    Ahmed, Ijaz; Hoorani, Hafeez; Aftab, Zia; Jan, J. A; Shariq Khan, M; Solaija, Tariq

    2006-01-01

    In this paper, results are presented from the beamtest in 2002 of the full-scale RE-2/2 prototype RPC chamber assembled in Pakistan. The results are mainly related with the efficiency, time resolution, and rate capability of this non-oiled RPC. The CMS collaboration has imposed strict criteria on the performance parameters for RPC's. These results show that prototype RPC's meet with all the CMS criteria and are suitable for installation in CMS detector.

  10. ISOCAM experiment cryogenic test results

    Science.gov (United States)

    de Sa, L.; Collaudin, B.

    The thermal requirements for ISOCAM, an IR camera to be mounted aboard the ISO satellite, are reviewed, and model predictions are matched with test results. The degree of model validation suggested by analytical prediction vs test results is described. Predictions of thermal conduction through mounting screws, from ball bearings, and of the heat distribution in the rotor and stator of a cryogenic stepper motor correlate well with actual test results. It is shown that ISOCAM meets the thermal requirements necessary for successful on-orbit operation. The model predicted such phenomena as 'chopped' motor function and the twofold increase in temperature resulting from continuous motor operation.

  11. Quadriceps tendon rupture - treatment results

    Directory of Open Access Journals (Sweden)

    Popov Iva

    2013-01-01

    Full Text Available Introduction. Quadriceps tendon rupture is a rare but rather serious injury. If this injury is not promptly recognized and early operated, it may lead to disability. This research was aimed at pointing out the results and complications of the quadriceps tendon rupture surgical treatment. Material and Methods. This retrospective multicentric study was conducted in a group of 29 patients (mostly elderly men. Lysholm knee scoring scale was used to evaluate the surgical results. The post-operative results were compared in relation to the type of tendon rupture reconstructions (acute or chronic, various surgical techniques, type of injuries (unilateral or bilateral as well as the presence or absence of comorbid risk factors in the patients. Results. The average value of a Lysholm score was 87.6. Excellent and satisfactory Lysholm score results dominated in our sample of patients. Better post-operative results were recorded in the group of patients without risk factors, in case of a bilateral injury, and in case of an acute injury. The best result was obtained after performing the reconstruction using anchors, and the worst result came after using Codivilla technique. Discussion and Conclusion. Early diagnosis and surgical treatment are an absolute imperative in management of this injury. We have not proven that a certain surgical technique has an advantage over the others. A comorbid risk factor is related to a lower Lysholm score. Despite a few cases of complications, we can conclude that the surgical treatment yields satisfactory results.

  12. Some Results behind Dividend Problems

    Institute of Scientific and Technical Information of China (English)

    Ming Zhou; Li Wei; Jun-yi Guo

    2006-01-01

    We consider the basic dividend problem of the compound Poisson model with constant barrier strategy. Some results concealed behind the dividend problem are made explicit in the present work. Different methods and some of which are firstly given in this paper. All these results presented certain direct relationship between some important actuary variables in classical risk theory is also revealed.

  13. Complexity Results in Epistemic Planning

    DEFF Research Database (Denmark)

    Bolander, Thomas; Jensen, Martin Holm; Schwarzentruber, Francois

    2015-01-01

    Epistemic planning is a very expressive framework that extends automated planning by the incorporation of dynamic epistemic logic (DEL). We provide complexity results on the plan existence problem for multi-agent planning tasks, focusing on purely epistemic actions with propositional preconditions......-hardness of the plan verification problem, which strengthens previous results on the complexity of DEL model checking....

  14. MER ARA pyroshock test results

    Science.gov (United States)

    Chang, Kurng Y.

    2004-01-01

    This paper presents the shock test results achieved in the MER ARA/brush motor pyroshock qualification. The results of MER flight system pyrofiring tests in comparison with the ARA shock test requirements are discussed herein. Alternate test methods were developed in an effort to qualify the critical MER equipment for adequate performance in the actual flight pyroshock condition.

  15. Top physics results at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Vickey, Trevor; /Illinois U., Urbana

    2005-05-01

    The most recent results on top quark physics at CDF are reported. Measurements of cross-section and mass are presented, and the status of single top quark production searches are discussed. The results obtained from probing various top quark properties are also presented.

  16. Customer interruption cost and results

    Energy Technology Data Exchange (ETDEWEB)

    Eua-Arporn, B.; Bisarnbutra, S. [Chulalongkorn Univ., Bangkok (Thailand)

    1997-12-31

    Results of a comprehensive study on short-term direct impacts and consumer interruption costs, incurred as a result of power supply interruption, were discussed. The emphasis was on questionnaire development, general responses and the average customer damage function of some selected sectors. The customer damage function was established for each category of customers (agriculture, industry, mining, wholesale, retail merchandising, residential, etc) as well as for different locations. Results showed that the average customer damage function depended mostly on customer category. Size and location were not significant factors. 5 refs., 7 tabs.

  17. Retrospective Evaluation of Colonoscopy Results

    Directory of Open Access Journals (Sweden)

    Yaşar M et al.

    2010-09-01

    Full Text Available Aim: The aim of this study is the retrospective evaluation of colonoscopy results between 2005 January- 2009 December in General Surgery Department of Düzce University.Materials and Methods: Admitted to our department with lower gastrointestinal symptoms, and colonoscopy is indicated 500 male and 538 female total 1038 patients were performed flexible colonoscopic examinations after bowel cleansing.Results: According to results of colonoscopic findings, 42.9% No pathology, 32.5% Hemorrhoids, 17.6% Anal fissures were detected.Conclusion: As a result of this study, half of patients admitted to our surgical clinic with lower gastrointestinal complaints have no pathology and in the other half of patients have various pathologies such as hemorrhoids and anal fissures.

  18. Results from NA61/SHINE

    Directory of Open Access Journals (Sweden)

    Unger M.

    2013-06-01

    Full Text Available In this paper we summarize recent results from NA61/SHINE relevant for heavy ion physics, neutrino oscillations and the interpretation of air showers induced by ultra-high energy cosmic rays.

  19. Disclosure of stress test results

    OpenAIRE

    Berlin, Mitchell

    2015-01-01

    Should regulatory bank examinations be made public? Regulators have argued that the confidentiality of the examination process promotes frank exchanges between bankers and examiners and that public disclosure of examination results could have a chilling effect. I examine the tradeoffs in a world in which examination results can be kept confidential, but regulatory interventions are observable by market participants, as they typically are for stress tests. Inducing banks to communicate truthfu...

  20. Electroweak results from the tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Wood, D. [Fermi National Accelerator Laboratory, Batavia, IL (United States)

    1997-01-01

    Electroweak results are presented from the CDF and DO experiments based on data collected in recent runs of the Fermilab Tevatron Collider. The measurements include the mass and width of the W boson, the production cross sections of the W and Z bosons, and the W charge asymmetry. Additional results come from studies of events with pairs of electroweak gauge bosons and include limits on anomalous couplings.

  1. Recent results on howard's algorithm

    DEFF Research Database (Denmark)

    Miltersen, P.B.

    2012-01-01

    is generally recognized as fast in practice, until recently, its worst case time complexity was poorly understood. However, a surge of results since 2009 has led us to a much more satisfactory understanding of the worst case time complexity of the algorithm in the various settings in which it applies....... In this talk, we shall survey these recent results and the open problems that remains....

  2. Selection of LHCb Physics Results

    Science.gov (United States)

    Schmidt, Burkhard

    2013-05-01

    LHCb is a dedicated flavour physics experiment at the LHC searching for physics beyond the Standard Model through precision measurements of CP-violating observables and the study of very rare decays of beauty- and charm-flavoured hadrons. In this article a selection of recent LHCb results is presented. Unless otherwise stated, the results are based on an integrated luminosity of 1 fb-1 accumulated during the year 2011 at √s = 7 TeV.

  3. New CDF results on diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Mesropian, Christina; /Rockefeller U.

    2006-12-01

    We report new diffraction results obtained by the CDF collaboration in proton-antiproton collisions at the Fermilab Tevatron collider at {radical}s=1.96 TeV. The first experimental evidence of exclusive dijet and diphoton production is presented. The exclusive results are discussed in context of the exclusive Higgs production at LHC. We also present the measurement of the Q{sup 2} and t dependence of the diffractive structure function.

  4. Results-Oriented Educational Leadership

    OpenAIRE

    Grãdinaru Cãtãlin; Toma Sorin-George

    2014-01-01

    All types of organizations, including educational ones, are results-oriented as increasing competition drives them towards achieving performance. Educational system reform has always represented a fundamental issue that concerns many stakeholders. In this respect, the implementation of a results-oriented approach in education demands responsible and efficient leadership. The aims of our paper are to briefly present the school as an educational organization, and to emphasize the relationship b...

  5. Heavy flavour results from ATLAS

    Directory of Open Access Journals (Sweden)

    Bell P. J.

    2012-06-01

    Full Text Available A selection of heavy-flavour physics results from the ATLAS experiment is presented, based on data collected in proton-proton collisions at the LHC during 2010. Differential cross-sections for the production of heavy flavours, charmonium and bottomonium states and D-mesons are presented and compared to various theoretical models. Results of B-hadron lifetime measurements are also reported.

  6. Planck 2013 results. I. Overview of products and scientific results

    CERN Document Server

    Ade, P.A.R.; Armitage-Caplan, C.; Arnaud, M.; Ashdown, M.; Atrio-Barandela, F.; Aumont, J.; Baccigalupi, C.; Banday, A.J.; Barreiro, R.B.; Bartelmann, M.; Bartlett, J.G.; Battaner, E.; Benabed, K.; Benoit, A.; Benoit-Levy, A.; Bernard, J.P.; Bersanelli, M.; Bielewicz, P.; Bobin, J.; Bock, J.J.; Bonaldi, A.; Bond, J.R.; Borrill, J.; Bouchet, F.R.; Boulanger, F.; Bowyer, J.W.; Bridges, M.; Bucher, M.; Burigana, C.; Butler, R.C.; Cappellini, B.; Cardoso, J.F.; Carr, R.; Casale, M.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.R.; Chen, X.; Chiang, L.Y.; Chiang, H.C.; Christensen, P.R.; Church, S.; Clements, D.L.; Colombi, S.; Colombo, L.P.L.; Couchot, F.; Coulais, A.; Crill, B.P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R.D.; Davis, R.J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.M.; Desert, F.X.; Dickinson, C.; Diego, J.M.; Dole, H.; Donzelli, S.; Dore, O.; Douspis, M.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Ensslin, T.A.; Eriksen, H.K.; Falgarone, E.; Finelli, F.; Foley, S.; Forni, O.; Frailis, M.; Franceschi, E.; Freschi, M.; Fromenteau, S.; Gaier, T.C.; Galeotta, S.; Gallegos, J.; Gandolfo, B.; Ganga, K.; Giard, M.; Giardino, G.; Giraud-Heraud, Y.; Gonzalez-Nuevo, J.; Gorski, K.M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Haissinski, J.; Hansen, F.K.; Hanson, D.; Harrison, D.; Helou, G.; Henrot-Versille, S.; Hernandez-Monteagudo, C.; Herranz, D.; Hildebrandt, S.R.; Hivon, E.; Hobson, M.; Holmes, W.A.; Hornstrup, A.; Hovest, W.; Huffenberger, K.M.; Jaffe, T.R.; Jaffe, A.H.; Jewell, J.; Jones, W.C.; Juvela, M.; Kangaslahti, P.; Keihanen, E.; Keskitalo, R.; Kisner, T.S.; Kneissl, R.; Knoche, J.; Knox, L.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lahteenmaki, A.; Lamarre, J.M.; Lasenby, A.; Laureijs, R.J.; Lawrence, C.R.; Le Jeune, M.; Leach, S.; Leahy, J.P.; Leonardi, R.; Leon-Tavares, J.; Leroy, C.; Lesgourgues, J.; Liguori, M.; Lilje, P.B.; Linden-Vornle, M.; Lopez-Caniego, M.; Lowe, S.; Lubin, P.M.; Macias-Perez, J.F.; Maffei, B.; Maino, D.; Mandolesi, N.; Maris, M.; Marshall, D.J.; Martin, P.G.; Martinez-Gonzalez, E.; Masi, S.; Matarrese, S.; Matthai, F.; Mazzotta, P.; McDonald, A.; McGehee, P.; Meinhold, P.R.; Melchiorri, A.; Melin, J.B.; Mendes, L.; Mennella, A.; Migliaccio, M.; Miniscalco, R.; Mitra, S.; Miville-Deschenes, M.A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J.A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C.B.; Norgaard-Nielsen, H.U.; North, C.; Noviello, F.; Novikov, D.; Novikov, I.; O'Dwyer, I.J.; Osborne, S.; Oxborrow, C.A.; Paci, F.; Pagano, L.; Pajot, F.; Paladini, R.; Paoletti, D.; Partridge, B.; Pasian, F.; Patanchon, G.; Pearson, D.; Pearson, T.J.; Perdereau, O.; Perotto, L.; Perrotta, F.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Platania, P.; Pointecouteau, E.; Polenta, G.; Ponthieu, N.; Popa, L.; Poutanen, T.; Pratt, G.W.; Prezeau, G.; Prunet, S.; Puget, J.L.; Rachen, J.P.; Reach, W.T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ringeval, C.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rossetti, M.; Roudier, G.; Rowan-Robinson, M.; Rubino-Martin, J.A.; Rusholme, B.; Salerno, E.; Sandri, M.; Santos, D.; Savini, G.; Scott, D.; Seiffert, M.D.; Shellard, E.P.S.; Smoot, G.F.; Spencer, L.D.; Starck, J.L.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sunyaev, R.; Sureau, F.; Sutton, D.; Suur-Uski, A.S.; Sygnet, J.F.; Tauber, J.A.; Tavagnacco, D.; Taylor, D.; Terenzi, L.; Texier, D.; Toffolatti, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Tuovinen, J.; Turler, M.; Tuttlebee, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, B.; Varis, J.; Vibert, L.; Vielva, P.; Villa, F.; Vittorio, N.; Wade, L.A.; Wandelt, B.D.; Watson, R.; Watson, C.; White, M.; White, S.D.M.; Wilkinson, A.; Yvon, D.; Zacchei, A.; Zonca, A.

    2014-01-01

    The ESA's Planck satellite, dedicated to studying the early universe, was launched on May 2009 and has been surveying the microwave and submillimetre sky since August 2009. In March 2013, ESA and the Planck Collaboration publicly released the initial cosmology products based on the first 15.5 months of Planck operations, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper describes the mission and its performance, and gives an overview of the processing and analysis of the data, the characteristics of the data, the main scientific results, and the science data products and papers in the release. Scientific results include robust support for the standard, six parameter LCDM model of cosmology and improved measurements for the parameters that define this model, including a highly significant deviation from scale invariance of the primordial power spectrum. The Planck values for some of these parameters and others derived from them are significantly different fr...

  7. Planck 2015 results. I. Overview of products and scientific results

    Science.gov (United States)

    Planck Collaboration; Adam, R.; Ade, P. A. R.; Aghanim, N.; Akrami, Y.; Alves, M. I. R.; Argüeso, F.; Arnaud, M.; Arroja, F.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Ballardini, M.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Bartolo, N.; Basak, S.; Battaglia, P.; Battaner, E.; Battye, R.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bertincourt, B.; Bielewicz, P.; Bikmaev, I.; Bock, J. J.; Böhringer, H.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burenin, R.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Carvalho, P.; Casaponsa, B.; Castex, G.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.-R.; Chiang, H. C.; Chluba, J.; Chon, G.; Christensen, P. R.; Church, S.; Clemens, M.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Comis, B.; Contreras, D.; Couchot, F.; Coulais, A.; Crill, B. P.; Cruz, M.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Di Valentino, E.; Dickinson, C.; Diego, J. M.; Dolag, K.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Eisenhardt, P. R. M.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Falgarone, E.; Fantaye, Y.; Farhang, M.; Feeney, S.; Fergusson, J.; Fernandez-Cobos, R.; Feroz, F.; Finelli, F.; Florido, E.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschet, C.; Franceschi, E.; Frejsel, A.; Frolov, A.; Galeotta, S.; Galli, S.; Ganga, K.; Gauthier, C.; Génova-Santos, R. T.; Gerbino, M.; Ghosh, T.; Giard, M.; Giraud-Héraud, Y.; Giusarma, E.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Grainge, K. J. B.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hamann, J.; Handley, W.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Heavens, A.; Helou, G.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huang, Z.; Huffenberger, K. M.; Hurier, G.; Ilić, S.; Jaffe, A. H.; Jaffe, T. R.; Jin, T.; Jones, W. C.; Juvela, M.; Karakci, A.; Keihänen, E.; Keskitalo, R.; Khamitov, I.; Kiiveri, K.; Kim, J.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Knox, L.; Krachmalnicoff, N.; Kunz, M.; Kurki-Suonio, H.; Lacasa, F.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Le Jeune, M.; Leahy, J. P.; Lellouch, E.; Leonardi, R.; León-Tavares, J.; Lesgourgues, J.; Levrier, F.; Lewis, A.; Liguori, M.; Lilje, P. B.; Lilley, M.; Linden-Vørnle, M.; Lindholm, V.; Liu, H.; López-Caniego, M.; Lubin, P. M.; Ma, Y.-Z.; Macías-Pérez, J. F.; Maggio, G.; Maino, D.; Mak, D. S. Y.; Mandolesi, N.; Mangilli, A.; Marchini, A.; Marcos-Caballero, A.; Marinucci, D.; Maris, M.; Marshall, D. J.; Martin, P. G.; Martinelli, M.; Martínez-González, E.; Masi, S.; Matarrese, S.; Mazzotta, P.; McEwen, J. D.; McGehee, P.; Mei, S.; Meinhold, P. R.; Melchiorri, A.; Melin, J.-B.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mikkelsen, K.; Millea, M.; Mitra, S.; Miville-Deschênes, M.-A.; Molinari, D.; Moneti, A.; Montier, L.; Moreno, R.; Morgante, G.; Mortlock, D.; Moss, A.; Mottet, S.; Münchmeyer, M.; Munshi, D.; Murphy, J. A.; Narimani, A.; Naselsky, P.; Nastasi, A.; Nati, F.; Natoli, P.; Negrello, M.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Olamaie, M.; Oppermann, N.; Orlando, E.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paladini, R.; Pandolfi, S.; Paoletti, D.; Partridge, B.; Pasian, F.; Patanchon, G.; Pearson, T. J.; Peel, M.; Peiris, H. V.; Pelkonen, V.-M.; Perdereau, O.; Perotto, L.; Perrott, Y. C.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pogosyan, D.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Racine, B.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Roman, M.; Romelli, E.; Rosset, C.; Rossetti, M.; Rotti, A.; Roudier, G.; Rouillé d'Orfeuil, B.; Rowan-Robinson, M.; Rubiño-Martín, J. A.; Ruiz-Granados, B.; Rumsey, C.; Rusholme, B.; Said, N.; Salvatelli, V.; Salvati, L.; Sandri, M.; Sanghera, H. S.; Santos, D.; Saunders, R. D. E.; Sauvé, A.; Savelainen, M.; Savini, G.; Schaefer, B. M.; Schammel, M. P.; Scott, D.; Seiffert, M. D.; Serra, P.; Shellard, E. P. S.; Shimwell, T. W.; Shiraishi, M.; Smith, K.; Souradeep, T.; Spencer, L. D.; Spinelli, M.; Stanford, S. A.; Stern, D.; Stolyarov, V.; Stompor, R.; Strong, A. W.; Sudiwala, R.; Sunyaev, R.; Sutter, P.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Tavagnacco, D.; Terenzi, L.; Texier, D.; Toffolatti, L.; Tomasi, M.; Tornikoski, M.; Tramonte, D.; Tristram, M.; Troja, A.; Trombetti, T.; Tucci, M.; Tuovinen, J.; Türler, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, F.; Vassallo, T.; Vibert, L.; Vidal, M.; Viel, M.; Vielva, P.; Villa, F.; Wade, L. A.; Walter, B.; Wandelt, B. D.; Watson, R.; Wehus, I. K.; Welikala, N.; Weller, J.; White, M.; White, S. D. M.; Wilkinson, A.; Yvon, D.; Zacchei, A.; Zibin, J. P.; Zonca, A.

    2016-09-01

    The European Space Agency's Planck satellite, which is dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013. In February 2015, ESA and the Planck Collaboration released the second set of cosmology products based ondata from the entire Planck mission, including both temperature and polarization, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the main characteristics of the data and the data products in the release, as well as the associated cosmological and astrophysical science results and papers. The data products include maps of the cosmic microwave background (CMB), the thermal Sunyaev-Zeldovich effect, diffuse foregrounds in temperature and polarization, catalogues of compact Galactic and extragalactic sources (including separate catalogues of Sunyaev-Zeldovich clusters and Galactic cold clumps), and extensive simulations of signals and noise used in assessing uncertainties and the performance of the analysis methods. The likelihood code used to assess cosmological models against the Planck data is described, along with a CMB lensing likelihood. Scientific results include cosmological parameters derived from CMB power spectra, gravitational lensing, and cluster counts, as well as constraints on inflation, non-Gaussianity, primordial magnetic fields, dark energy, and modified gravity, and new results on low-frequency Galactic foregrounds.

  8. Results from PHENIX at RHIC

    CERN Document Server

    Tannenbaum, M J

    2009-01-01

    Results from PHENIX at RHIC in p-p and Au+Au collisions are presented from the perspective of measurements in p-p collisions at the CERN ISR which serve as a basis for many of the techniques used. Notable results include the equality of the suppression of inclusive pi0 and direct electrons (from the decay of heavy quarks) in the range of transverse momentuum 4 < pT < 9 GeV/c in central Au+Au collisions. This result appears to strongly disfavor the explanation of suppression as due to radiative energy loss of partons traversing a Quark Gluon Plasma but opens up a fundamental discussion of how Fermions get mass, whether all six quarks are nearly massless in a QGP and how to test this.

  9. Catastrophic disruption experiments: Recent results

    Science.gov (United States)

    Martelli, G.; Ryan, E. V.; Nakamura, A. M.; Giblin, I.

    1994-01-01

    This paper presents a review of the progress in the field of catastrophic disruption experiments over the past 4 years, since the publication of the review paper by Fujiwara et al. (1989). We describe the development of new techniques to produce shattering impacts relevant to the study of the collisional evolution of the asteroids, and summarize the results from numerous experiments which have been performed to date, using a variety of materials for both the impactor and the targets. Some of these, such as ice-on-ice, loose aggregates and pressurized targets, are quite new and have provided novel and exciting results. Some of the gaps existing previously in the data on fragment ejection-angle distributions, as well as translational and rotational velocity fields (including fine fragments) have been filled, and these new results will be surveyed.

  10. Supersymmetry results at the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Manca, Giulia; /Liverpool U.

    2005-05-01

    The Run II physics programme of the Tevatron is proceeding with more than 300 pb{sup -1} of analysis quality data, collected at a center-of-mass energy of 1.96 TeV. Searches for supersymmetric particles are starting to set new limits, improving over the LEP and Run I results and exploring new regions of parameter space. They present recent results in Supersymmetry with the upgraded CDF and D0 detectors and give some prospects for the future of these searches.

  11. First results from SAGE II

    International Nuclear Information System (INIS)

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first five runs of SAGE II give a capture rate of 76-18+21 (stat) -7+5 (sys) SNU. combined with the SAGE I result, the capture rate is 74-12+13 (stat) -7+5 (sys) SNU. This represents only 56%--60% of the capture rate predicted by different Standard Solar Models

  12. VERITAS: Status and Early Results

    International Nuclear Information System (INIS)

    A new generation of observatories have revolutionized the study of the very high energy gamma-ray sky. The recently-commissioned VERITAS observatory, an array of four 12 m diameter imaging atmospheric Cherenkov telescopes designed to search for gamma-ray sources in the energy band between 100 GeV and 50 TeV, is one of these new instruments. VERITAS has been taking scientific data with three or more telescopes since November 2006. We discuss the thrust of the VERITAS observation program and present results from these early observations, including new results on the sources IC433, LSI+61 303, 1ES 1218+304 and M87. (author)

  13. Neutrinos: summary of new results

    International Nuclear Information System (INIS)

    After a short presentation of the neutrino mass-mixing parameters, the core of the paper will be devoted to the recent experimental results from SNO, KamLAND and K2K. As a conclusion, I will discuss possible CP violation measurements with neutrinos. The paper is structured as follows: 1 Neutrino Oscillations Physics; 2 New results in solar neutrinos; 2.1 The SNO experiment; 2.2 The KamLAND experiment; 4 Opening the road toward a measurement of neutrino CP violation?

  14. Audit result and its users

    OpenAIRE

    Shalimova Nataliya S.

    2014-01-01

    The article identifies essence of the “audit result” and “users of audit result” notions and characteristics of the key audit results user. It shows that in order to give a wide characteristic of users it is expedient to unite all objects, which could be used (audit report, fact of refusal to conduct audit and information that is submitted to managers in the process of audit) with the term “audit result” and classify it depending on the terms of submission by final and intermediate result. Th...

  15. Communicating Performance Assessments Results - 13609

    International Nuclear Information System (INIS)

    The F-Area Tank Farms (FTF) and H-Area Tank Farm (HTF) are owned by the U.S. Department of Energy (DOE) and operated by Savannah River Remediation LLC (SRR), Liquid Waste Operations contractor at DOE's Savannah River Site (SRS). The FTF and HTF are active radioactive waste storage and treatment facilities consisting of 51 carbon steel waste tanks and ancillary equipment such as transfer lines, evaporators and pump tanks. Performance Assessments (PAs) for each Tank Farm have been prepared to support the eventual closure of the underground radioactive waste tanks and ancillary equipment. PAs provide the technical bases and results to be used in subsequent documents to demonstrate compliance with the pertinent requirements for final closure of the Tank Farms. The Tank Farms are subject to a number of regulatory requirements. The State regulates Tank Farm operations through an industrial waste water permit and through a Federal Facility Agreement approved by the State, DOE and the Environmental Protection Agency (EPA). Closure documentation will include State-approved Tank Farm Closure Plans and tank-specific closure modules utilizing information from the PAs. For this reason, the State of South Carolina and the EPA must be involved in the performance assessment review process. The residual material remaining after tank cleaning is also subject to reclassification prior to closure via a waste determination pursuant to Section 3116 of the Ronald W. Reagan National Defense Authorization Act of Fiscal Year 2005. PAs are performance-based, risk-informed analyses of the fate and transport of FTF and HTF residual wastes following final closure of the Tank Farms. Since the PAs serve as the primary risk assessment tools in evaluating readiness for closure, it is vital that PA conclusions be communicated effectively. In the course of developing the FTF and HTF PAs, several lessons learned have emerged regarding communicating PA results. When communicating PA results it is

  16. Recent results in neutrino physics

    CERN Document Server

    Naumov, Dmitry V

    2011-01-01

    This manuscript is a shorthand version of my talk given at Odessa Gamov School on Astronomy, Cosmology and Beyond (22-28 August 2011, Odessa, Ukraine). Within this note we very briefly review the main achievements, new results and open problems in neutrino physics of today.

  17. Latest results from B factories

    CERN Document Server

    Ben Haim, Eli

    2015-01-01

    I will briefly review recent results from Babar and Belle. For example, I will discuss probes for new physics in radiative penguin decays and the CP asymmetry in B0-B0bar mixing. I will also discuss direct searches for new physics, such as a light Higgs resonance or long lived particles.

  18. ATLAS H(125) difermion results

    CERN Document Server

    Shabalina, Elizaveta; The ATLAS collaboration

    2016-01-01

    We present a summary of the recent measurements of the Standard Model Higgs production in fermionic decay modes. New results are presented for the dimuon Higgs decays, for Higgs decaying in a $b\\bar{b}$ pair in the VH and ttH production modes and in the VBF channel with photon production.

  19. Recent results from KLOE experiment

    CERN Document Server

    Ambrosino, F; Antonelli, M; Archilli, F; Bacci, C; Beltrame, P; Bencivenni, G; Bertolucci, S; Bini, C; Bloise, C; Bocchetta, S; Bossi, F; Branchini, P; Caloi, R; Campana, P; Capon, G; Capussela, T; Ceradini, F; Cesario, F; Chi, S; Chiefari, G; Ciambrone, P; Crucianelli, F; De Lucia, E; De Santis, A; De Simone, P; De Zorzi, G; Denig, A; Di Domenico, A; Di Donato, C; Di Micco, B; Doria, A; Dreucci, M; Felici, G; Ferrari, A; Ferrer, M L; Fiore, S; Forti, C; Franzini, P; Gatti, C; Gauzzi, P; Giovannella, S; Gorini, E; Graziani, E; Kluge, W; Kulikov, V; Lacava, F; Lanfranchi, G; Lee-Franzini, J; Leone, D; Martini, M; Massarotti, P; Mei, W; Meola, S; Miscetti, S; Moulson, M; Müller, S; Murtas, F; Napolitano, M; Nguyen, F; Palutan, M; Pasqualucci, E; Passeri, A; Patera, V; Perfetto, F; Primavera, M; Santangelo, P; Saracino, G; Sciascia, B; Sciubba, A; Sibidanov, A; Spadaro, T; Testa, M; Tortora, L; Valente, P; Venanzoni, G; Versaci, R; Xu, G

    2008-01-01

    We report the newest results from the KLOE experiment on hadronic physics, such as the parameters of scalars f0 and a0, the eta meson mass measurements and dynamics, the first observation of the eta -> p+p-e+e- rare decay, and study of e+e- -> omega p0 cross section around the phi resonance.

  20. Striking results with bouncing balls

    NARCIS (Netherlands)

    A. Heck; T. Ellermeijer; E. Kędzierska

    2008-01-01

    In a laboratory activity students study the behaviour of a bouncing ball. With the help of a high-speed camera they can study the motion in detail. Computer modelling enables them to relate the measurement results to the theory. They experience that reality (measurements) is not automatically in lin

  1. New ATLAS Higgs physics results

    CERN Document Server

    CERN. Geneva

    2014-01-01

    New Higgs physics results from the ATLAS experiment using the full Run-1 LHC dataset, corresponding to an integrated luminosity of approximately 25 fb-1, of proton-proton collisions at 7 TeV and 8 TeV, will be presented.

  2. B0s Oscillation Results

    CERN Document Server

    Willocq, S

    2002-01-01

    We review new studies of the time dependence of B0s - B0s-bar mixing by the ALEPH, DELPHI and SLD Collaborations, with an emphasis on the different analysis methods used. Combining all available results yields a preliminary lower limit on the oscillation frequency of dms > 14.4 ps-1 at the 95% C.L.

  3. Recent Results from the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Demorden, L.

    1998-06-01

    We review recent results from fixed-target and collider experiments at the Fermilab Tevatron. Among the topics discussed are jet production rates, {alpha}{sub S} measurements, the {anti d}/{anti u} ratio in the proton sea, diffraction, heavy quark physics and leptoquark searches.

  4. Results from PLUTO at PETRA

    International Nuclear Information System (INIS)

    Results obtained at the e+e- storage ring PETRA by the PLUTO collaboration at c.m. energies of 13, 17 and 27.4 GeV are presented. New limits on QED cut-off parameters are determined from Bhabha scattering; at 27.4 GeV the limits are Λsub(+) > 38 GeV and Λsub(-) > 60 GeV. The measured values of the total hadronic cross section, and the study of the jet character of the hadronic events are well consistent with the expected production of b mesons (with qsub(b) = 1/3), but do not require additional new quarks with charge 2/3. Hadronic events from two-photon exchange processes are observed with comparable rates as events from one-photon exchange. First results on the hadronic cross section in γγ collisions are given. (orig.)

  5. PHENIX recent heavy flavor results

    CERN Document Server

    ,

    2014-01-01

    Cold nuclear matter (CNM) effects provide an important baseline for the interpretation of data in heavy ion collisions. Such effects include nuclear shadowing, Cronin effect, and initial patron energy loss, and it is interesting to study the dependence on impact parameter and kinematic region. Heavy quark production is a good measurement to probe the CNM effects particularly on gluons, since heavy quarks are mainly produced via gluon fusions at RHIC energy. The PHENIX experiment has experiment has ability to study the CNM effects by measuring heavy quark production in $d$$+$Au collisions at variety of kinematic ranges. Comparisons of heavy quark production at different rapidities allow us to study modification of gluon density function in the Au nucleus depending on momentum fraction. Furthermore, comparisons to the results from heavy ion collisions (Au$+$Au and Cu$+$Cu) measured by PHENIX provide insight into the role of CNM effects in such collisions. Recent PHENIX results on heavy quark production are disc...

  6. Recent results on tau decays

    International Nuclear Information System (INIS)

    New preliminary ARGUS results on τ decays are presented. We have measured the inclusive 3-prong branching ratio as well as the exclusive branching ratios for 6 major τ decay channels: τ- → ε-ν-bareντ.τ- → μ-ν-barμντ.τ- → π- /K-ντ.τ- → π-π-π-ντ.τ- → π-π0ντ and τ- → π- π- π+ π0 ντ†. Our results are in contradiction to the recent CELLO measurements, which indicate that the τ decay problem disappeared. A search was made for 26 different neutrinoless τ decays. No evidence has been found, that the τ decay problem might be connected to such neutrinoless decays. In addition, the hadronic final states of τ decays into π π0ντ and π-π-π+ντ have been analyzed. (author)

  7. First Physics Results from ALICE

    International Nuclear Information System (INIS)

    ALICE is the LHC experiment dedicated to the study of heavy-ion collisions. The main purpose of ALICE is to investigate the properties of a state of deconfined nuclear matter, the Quark Gluon Plasma. Heavy flavour measurements will play a crucial role in this investigation. The physics programme of ALICE has started by studying proton-proton collisions at unprecedented high energies. We will present the first results on open heavy flavour and quarkonia in proton-proton collisions at √s = 7 TeV measured by the ALICE experiment at both mid- and forward-rapidities. We will conclude with the prospects for heavy flavour and quarkonium measurements in both proton-proton and nucleus-nucleus collisions. Also presented are first results of neutral meson reconstruction and its perspectives, as well as further physics studies. (author)

  8. Forget about data, deliver results

    Science.gov (United States)

    Walter, Roland

    2015-12-01

    High-energy astrophysics space missions have pioneered and demonstrated the power of legacy data sets for generating new discoveries, especially when analysed in ways original researchers could not have anticipated. The only way to ensure that the data of present observatories can be effectively used in the future is to allow users to perform on-the-fly data analysis to produce straightforwardly scientific results for any sky position, time and energy intervals without requiring mission specific software or detailed instrumental knowledge. Providing a straightforward interface to complex data and data analysis makes the data and the process of generating science results available to the public and higher education and promotes the visibility of the investment in science to the society. This is a fundamental step to transmit the values of science and to evolve towards a knowledge society.

  9. Basic results on braid groups

    CERN Document Server

    Gonzalez-Meneses, Juan

    2010-01-01

    These are Lecture Notes of a course given by the author at the French-Spanish School "Tresses in Pau", held in Pau (France) in October 2009. It is basically an introduction to distinct approaches and techniques that can be used to show results in braid groups. Using these techniques we provide several proofs of well known results in braid groups, namely the correctness of Artin's presentation, that the braid group is torsion free, or that its center is generated by the full twist. We also recall some solutions of the word and conjugacy problems, and that roots of a braid are always conjugate. We also describe the centralizer of a given braid. Most proofs are classical ones, using modern terminology. I have chosen those which I find simpler or more beautiful.

  10. First results from SAGE II

    Energy Technology Data Exchange (ETDEWEB)

    Aburashitov, J.N.; Faizov, E.L.; Gavrin, V.N.; Gusev, A.O.; Kalikhov, A.V.; Knodel, T.V.; Knyshenko, I.I.; Kornoukhov, V.N.; Mirmov, I.N.; Pshukov, A.M.; Shalagin, A.M.; Shikhin, A.A.; Timofeyev, P.V.; Veretenkin, E.P.; Vermul, V.M.; Zatsepin, G.T. [Institute for Nuclear Research, Russian Academy of Sciences Moscow, 117312 (Russian Federation); Bowles, T.J.; Nico, J.S.; Teasdale, W.A.; Wark, D.L.; Wilkerson, J.F. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Cleveland, B.T.; Daily, T.; Davis, R. Jr.; Lande, K.; Lee, C.K.; Wildenhain, P.W. [University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Elliott, S.R. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Cherry, M.L. [Louisiana State University, Baton Rouge, Louisiana 70803 (United States)

    1995-07-10

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first five runs of SAGE II give a capture rate of 76{sup +21}{sub {minus}18}(stat){sup +5}{sub {minus}7}(sys) SNU. Combined with the SAGE I result, the capture rate is 74{sup +13}{sub {minus}12}(stat){sup +5}{sub {minus}7}(sys) SNU. This represents only 56%--60% of the capture rate predicted by different Standard Solar Models. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  11. First Physics Results from ALICE

    Energy Technology Data Exchange (ETDEWEB)

    Peressounko, Dmitri [Russian Research Centre - RRC ' Kurchatov Institute' , Kurchatov sq.1, Moscow, 123182 (Russian Federation); Castillo Castellanos, Javier [service de physique nucleaire - SPhN, IRFU, CEA-Saclay, 91191 Gif-sur-Yvette Cedex (France); Belikov, Iouri [Institut Pluridisciplinaire Hubert Curien - IPHC, 23 rue du loess - BP28, 67037 Strasbourg cedex 2 (France)

    2010-07-01

    ALICE is the LHC experiment dedicated to the study of heavy-ion collisions. The main purpose of ALICE is to investigate the properties of a state of deconfined nuclear matter, the Quark Gluon Plasma. Heavy flavour measurements will play a crucial role in this investigation. The physics programme of ALICE has started by studying proton-proton collisions at unprecedented high energies. We will present the first results on open heavy flavour and quarkonia in proton-proton collisions at {radical}s = 7 TeV measured by the ALICE experiment at both mid- and forward-rapidities. We will conclude with the prospects for heavy flavour and quarkonium measurements in both proton-proton and nucleus-nucleus collisions. Also presented are first results of neutral meson reconstruction and its perspectives, as well as further physics studies. (author)

  12. Results from the NOMAD experiment

    CERN Document Server

    Lupi, A

    2000-01-01

    he NOMAD experiment has been searching for νμ ↔ ντ oscillations by looking for the appearance of τ− in events from the CERN-SPS neutrino beam. With some improvements in the analysis techniques with respect to the previous published results and including data from 1995 to 1997, no evidence for oscillations is found, resulting in an updated limit in the oscillation probability of P(νμ↔ντ) < 0.6 × 10−3 at 90% C.L. This corresponds to a limit on the oscillation mixing angle of sin22θμτ < 1.2 × 10−3 for large Δm2.

  13. Overview of recent ATLAS results

    CERN Document Server

    Nikolic-Audit, Irena; The ATLAS collaboration

    2013-01-01

    The ATLAS experiment at the LHC collider has been successfully taking data since the end of 2009 in proton-proton collisions at center of mass energies of 7 and 8 TeV, and in heavy ion collisions. The ATLAS detector has been designed to cover a wide range of physics topics, from the search for the Higgs boson (which will be covered in a separate contribution), precision measurements of Standard Model physics, heavy flavor physics, and to maximize the potential for the discovery of new physics. In this talk, some of the most important recent ATLAS results will be given for the Standard Model measurements, the searches for supersymetry and exotica and for the heavy ion results.

  14. VERITAS: Status and Latest Results

    CERN Document Server

    Maier, G

    2007-01-01

    VERITAS is an atmospheric Cherenkov telescope array designed to study astrophysi cal sources of very-high-energy gamma radiation. Located in southern Arizona, USA, the array consists of four 12m-diameter imaging Cherenkov telescopes. All four telescopes have been deployed at the basecamp of the Whipple Observatory and began full operation in early 2007. This paper describes the operational status of VERITAS, outlines the initial performance parameters of the instrument, and presents the latest results that have been obtained.

  15. Results from the FDIRC prototype

    International Nuclear Information System (INIS)

    We present results from a novel Cherenkov imaging detector called the Focusing DIRC (FDIRC). This detector was designed as a prototype of the particle identification system for the SuperB experiment, and comprises 1/12 of the SuperB barrel azimuthal coverage with partial electronics implementation. The prototype was tested in the SLAC Cosmic Ray Telescope (CRT) which provides 3-D muon tracking with an angular resolution of ∼1.5 mrad, track position resolution of 5–6 mm, start time resolution of 70 ps, and a muon low-energy cutoff of ∼2 GeV provided by an iron range stack. The quartz focusing photon camera couples to a full-size BaBar DIRC bar box and is read out by 12 Hamamatsu H8500 MaPMTs providing 768 pixels. We used IRS2 waveform digitizing electronics to read out the MaPMTs. We present several results from our on-going development activities that demonstrate that the new optics design works very well, including: (a) single photon Cherenkov angle resolutions with and without chromatic corrections, (b) S/N ratio between the Cherenkov peak and background, which consists primarily of ambiguities in possible photon paths to a given pixel, (c) dTOP=TOPmeasured–TOPexpected resolutions, and (d) performance of the detector in the presence of high-rate backgrounds. We also describe data analysis methods and point out limits of the present performance. - Highlights: • We present results from a novel Cherenkov imaging detector called the Focusing DIRC (FDIRC). • The prototype was tested in the SLAC Cosmic Ray Telescope (CRT) which provides 3-D muon tracking. • We present several results from our on-going development activities that demonstrate that new optics design works very well. • We describe data analysis methods and point out limits of the present performance

  16. LHC Results Highlights (CLASHEP 2013)

    CERN Document Server

    Gonzalez, O

    2015-01-01

    The good performance of the LHC provided enough data at 7 TeV and 8 TeV to allow the experiments to perform very competitive measurements and to expand the knowledge about the fundamental interaction far beyond that from previous colliders. This report summarizes the highlights of the results obtained with these data samples by the four large experiments, covering all the topics of the physics program and focusing on those exploiting the possibilities of the LHC.

  17. SPQR -- Spectroscopy: Prospects, Questions & Results

    Energy Technology Data Exchange (ETDEWEB)

    Pennington, Michael R. [JLAB

    2014-06-01

    Tremendous progress has been made in mapping out the spectrum of hadrons over the past decade with plans to make further advances in the decade ahead. Baryons and mesons, both expected and unexpected, have been found, the results of precision experiments often with polarized beams, polarized targets and sometimes polarization of the final states. All these hadrons generate poles in the complex energy plane that are consequences of strong coupling QCD. They reveal how this works.

  18. Results from the B Factories

    Energy Technology Data Exchange (ETDEWEB)

    Bevan, A.; /Queen Mary, U. of London

    2009-01-08

    These proceedings are based on lectures given at the Helmholtz International Summer School Heavy Quark Physics at the Bogoliubov Laboratory of Theoretical Physics, Dubna, Russia, during August 2008. I review the current status of CP violation in B meson decays from the B factories. These results can be used, along with measurements of the sides of the Unitarity Triangle, to test the CKM mechanism. In addition I discuss experimental studies of B decays to final states with 'spin-one' particles.

  19. Recent results from ATLAS experiment

    CERN Document Server

    Smirnov, Sergei; The ATLAS collaboration

    2016-01-01

    The 2nd LHC run has started in 2015 with a pp centre-of-mass collision energy of 13 TeV and ATLAS has taken more than 20 fb-1 of data at the new energy by 2016 summer. In this talk, an overview is given on the ATLAS data taking and the improvements made to the ATLAS experiment during the 2-year shutdown 2013/2014. Selected new results from the recent data analysis from ATLAS is also presented.

  20. Evaluating the RELM Test Results

    OpenAIRE

    Sachs, Michael K.; Ya-Ting Lee; Turcotte, Donald L.; Holliday, James R.; Rundle, John B.

    2012-01-01

    We consider implications of the Regional Earthquake Likelihood Models (RELM) test results with regard to earthquake forecasting. Prospective forecasts were solicited for M≥4.95 earthquakes in California during the period 2006–2010. During this period 31 earthquakes occurred in the test region with M≥4.95. We consider five forecasts that were submitted for the test. We compare the forecasts utilizing forecast verification methodology developed in the atmospheric sciences, specifically for torn...

  1. SPQR -- Spectroscopy: Prospects, Questions & Results

    CERN Document Server

    Pennington, M R

    2014-01-01

    Tremendous progress has been made in mapping out the spectrum of hadrons over the past decade with plans to make further advances in the decade ahead. Baryons and mesons, both expected and unexpected, have been found, the results of precision experiments often with polarized beams, polarized targets and sometimes polarization of the final states. All these hadrons generate poles in the complex energy plane that are consequences of strong coupling QCD. They reveal how this works.

  2. Recent HERMES Results on DVCS

    OpenAIRE

    Krauss, B.; collaboration, for the HERMES

    2005-01-01

    The interference of Deeply Virtual Compton Scattering (DVCS) and Bremsstrahlung leads to a beam-charge asymmetry that can be observed for exclusive photon production in the collision of high energy leptons and nucleons/nuclei. Recent results for a hydrogen and a deuterium target are reported and a consistent tendency for a rise of the cosine phi coefficient with momentum transfer |t| has been found.

  3. Geometric Results for Compressible Magnetohydrodynamics

    OpenAIRE

    Arter, Wayne

    2013-01-01

    Recently, compressible magnetohydrodynamics (MHD) has been elegantly formulated in terms of Lie derivatives. This paper exploits the geometrical properties of the Lie bracket to give new insights into the properties of compressible MHD behaviour, both with and without feedback of the magnetic field on the flow. These results are expected to be useful for the solution of MHD equations in both tokamak fusion experiments and space plasmas.

  4. Audit result and its users

    Directory of Open Access Journals (Sweden)

    Shalimova Nataliya S.

    2014-01-01

    Full Text Available The article identifies essence of the “audit result” and “users of audit result” notions and characteristics of the key audit results user. It shows that in order to give a wide characteristic of users it is expedient to unite all objects, which could be used (audit report, fact of refusal to conduct audit and information that is submitted to managers in the process of audit with the term “audit result” and classify it depending on the terms of submission by final and intermediate result. The article offers to define audit results user as a person, persons or category of persons for whom the auditor prepares the audit report and, in cases, envisaged by international standards of the audit and domestic legislative and regulatory acts, provides other additional information concerning audit issues. In order to identify the key audit results user the article distributes all audit tasks into two groups depending on possibilities of identification of users. The article proves that the key user should be identified especially in cases of a mandatory audit and this process should go in interconnection with the mechanism of allocation of a key user of financial reports. It offers to consider external users with direct financial interests, who cannot request economic subjects directly to provide information and who should rely on general financial reports and audit report when receiving significant portion of information they need, as the key user. The article makes proposals on specification of the categorical mechanism in the sphere of audit, which are the basis for audit quality assessment, identification of possibilities and conditions of appearance of the necessary and sufficient trust to the auditor opinion.

  5. Planck 2015 results. I. Overview of products and scientific results

    CERN Document Server

    Adam, R; Aghanim, N.; Akrami, Y.; Alves, M.I.R.; Arnaud, M.; Arroja, F.; Aumont, J.; Baccigalupi, C.; Ballardini, M.; Banday, A.J.; Barreiro, R.B.; Bartlett, J.G.; Bartolo, N.; Basak, S.; Battaglia, P.; Battaner, E.; Battye, R.; Benabed, K.; Benoit, A.; Benoit-Levy, A.; Bernard, J.P.; Bersanelli, M.; Bertincourt, B.; Bielewicz, P.; Bonaldi, A.; Bonavera, L.; Bond, J.R.; Borrill, J.; Bouchet, F.R.; Boulanger, F.; Bucher, M.; Burigana, C.; Butler, R.C.; Calabrese, E.; Cardoso, J.F.; Carvalho, P.; Casaponsa, B.; Castex, G.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.R.; Chiang, H.C.; Chluba, J.; Christensen, P.R.; Church, S.; Clemens, M.; Clements, D.L.; Colombi, S.; Colombo, L.P.L.; Combet, C.; Comis, B.; Contreras, D.; Couchot, F.; Coulais, A.; Crill, B.P.; Cruz, M.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R.D.; Davis, R.J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.M.; Desert, F.X.; Di Valentino, E.; Dickinson, C.; Diego, J.M.; Dolag, K.; Dole, H.; Donzelli, S.; Dore, O.; Douspis, M.; Ducout, A.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Eisenhardt, P.R.M.; Elsner, F.; Ensslin, T.A.; Eriksen, H.K.; Falgarone, E.; Fantaye, Y.; Farhang, M.; Feeney, S.; Fergusson, J.; Fernandez-Cobos, R.; Feroz, F.; Finelli, F.; Florido, E.; Forni, O.; Frailis, M.; Fraisse, A.A.; Franceschet, C.; Franceschi, E.; Frejsel, A.; Frolov, A.; Galeotta, S.; Galli, S.; Ganga, K.; Gauthier, C.; Genova-Santos, R.T.; Gerbino, M.; Ghosh, T.; Giard, M.; Giraud-Heraud, Y.; Giusarma, E.; Gjerlow, E.; Gonzalez-Nuevo, J.; Gorski, K.M.; Grainge, K.J.B.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J.E.; Hamann, J.; Handley, W.; Hansen, F.K.; Hanson, D.; Harrison, D.L.; Heavens, A.; Helou, G.; Henrot-Versille, S.; Hernandez-Monteagudo, C.; Herranz, D.; Hildebrandt, S.R.; Hivon, E.; Hobson, M.; Holmes, W.A.; Hornstrup, A.; Hovest, W.; Huang, Z.; Huffenberger, K.M.; Hurier, G.; Ilic, S.; Jaffe, A.H.; Jaffe, T.R.; Jin, T.; Jones, W.C.; Juvela, M.; Karakci, A.; Keihanen, E.; Keskitalo, R.; Kiiveri, K.; Kim, J.; Kisner, T.S.; Kneissl, R.; Knoche, J.; Krachmalnicoff, N.; Kunz, M.; Kurki-Suonio, H.; Lacasa, F.; Lagache, G.; Lahteenmaki, A.; Lamarre, J.M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Lawrence, C.R.; Le Jeune, M.; Leahy, J.P.; Lellouch, E.; Leonardi, R.; Leon-Tavares, J.; Lesgourgues, J.; Levrier, F.; Lewis, A.; Liguori, M.; Lilje, P.B.; Linden-Vornle, M.; Lindholm, V.; Liu, H.; Lopez-Caniego, M.; Lubin, P.M.; Ma, Y.Z.; Macias-Perez, J.F.; Maggio, G.; Mak, D.S.Y.; Mandolesi, N.; Mangilli, A.; Marchini, A.; Marcos-Caballero, A.; Marinucci, D.; Marshall, D.J.; Martin, P.G.; Martinelli, M.; Martinez-Gonzalez, E.; Masi, S.; Matarrese, S.; Mazzotta, P.; McEwen, J.D.; McGehee, P.; Mei, S.; Meinhold, P.R.; Melchiorri, A.; Melin, J.B.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mikkelsen, K.; Mitra, S.; Miville-Deschenes, M.A.; Molinari, D.; Moneti, A.; Montier, L.; Moreno, R.; Morgante, G.; Mortlock, D.; Moss, A.; Mottet, S.; Muenchmeyer, M.; Munshi, D.; Murphy, J.A.; Narimani, A.; Naselsky, P.; Nastasi, A.; Nati, F.; Natoli, P.; Negrello, M.; Netterfield, C.B.; Norgaard-Nielsen, H.U.; Noviello, F.; Novikov, D.; Novikov, I.; Olamaie, M.; Oppermann, N.; Orlando, E.; Oxborrow, C.A.; Paci, F.; Pagano, L.; Pajot, F.; Paladini, R.; Pandolfi, S.; Paoletti, D.; Partridge, B.; Pasian, F.; Patanchon, G.; Pearson, T.J.; Peel, M.; Peiris, H.V.; Pelkonen, V.M.; Perdereau, O.; Perotto, L.; Perrott, Y.C.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pogosyan, D.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G.W.; Prezeau, G.; Prunet, S.; Puget, J.L.; Rachen, J.P.; Racine, B.; Reach, W.T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Roman, M.; Romelli, E.; Rosset, C.; Rossetti, M.; Rotti, A.; Roudier, G.; d'Orfeuil, B.Rouille; Rowan-Robinson, M.; Rubino-Martin, J.A.; Ruiz-Granados, B.; Rumsey, C.; Rusholme, B.; Said, N.; Salvatelli, V.; Salvati, L.; Sandri, M.; Sanghera, H.S.; Santos, D.; Saunders, R.D.E.; Sauve, A.; Savelainen, M.; Savini, G.; Schaefer, B.M.; Schammel, M.P.; Scott, D.; Seiffert, M.D.; Serra, P.; Shellard, E.P.S.; Shimwell, T.W.; Shiraishi, M.; Smith, K.; Souradeep, T.; Spencer, L.D.; Spinelli, M.; Stanford, S.A.; Stern, D.; Stolyarov, V.; Stompor, R.; Strong, A.W.; Sudiwala, R.; Sunyaev, R.; Sutter, P.; Sutton, D.; Suur-Uski, A.S.; Sygnet, J.F.; Tauber, J.A.; Tavagnacco, D.; Terenzi, L.; Texier, D.; Toffolatti, L.; Tomasi, M.; Tornikoski, M.; Tristram, M.; Troja, A.; Trombetti, T.; Tucci, M.; Tuovinen, J.; Turler, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, B.; Vassallo, T.; Vidal, M.; Viel, M.; Vielva, P.; Villa, F.; Wade, L.A.; Walter, B.; Wandelt, B.D.; Watson, R.; Wehus, I.K.; Welikala, N.; Weller, J.; White, M.; White, S.D.M.; Wilkinson, A.; Yvon, D.; Zacchei, A.; Zibin, J.P.; Zonca, A.

    2015-01-01

    The European Space Agency's Planck satellite, dedicated to studying the early Universe and its subsequent evolution, was launched 14~May 2009 and scanned the microwave and submillimetre sky continuously between 12~August 2009 and 23~October 2013. In February~2015, ESA and the Planck Collaboration released the second set of cosmology products based on data from the entire Planck mission, including both temperature and polarization, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the main characteristics of the data and the data products in the release, as well as the associated cosmological and astrophysical science results and papers. The science products include maps of the cosmic microwave background (CMB), the thermal Sunyaev-Zeldovich effect, and diffuse foregrounds in temperature and polarization, catalogues of compact Galactic and extragalactic sources (including separate catalogues of Sunyaev-Zeldovich clusters and Galactic col...

  6. Presentation of RTE results 2003

    International Nuclear Information System (INIS)

    In 2003, RTE recorded a clear improvement in its financial results, and continued its debt reduction programme. The financial year 2003 was marked by a clear improvement in RTE's financial performance: results exceeded objectives, with turnover growing strongly, net income reached levels almost three times higher than those recorded in 2002, the economic rate of return rose to 7.1%, and debt was reduced by 470 Meuros. These results are explained by the substantial improvement in productivity, which has risen by 5% per year on average over the last three years. Net income has almost tripled due to RTE's improved productivity completed by a significant rise in its turnover and stabilizing operating costs RTE's finances therefore remain healthy, enabling the company to continue its debt reduction programme. Satisfactory economic and financial rates of return. Deadlines facing RTE in 2004: in application of the second European Directive, adopted on 26 June 2003, RTE faces two major deadlines in 2004: - the implementation of the 2. phase in the process of opening up the French electricity market, - its legal independence. On 1 July 2004, the market will be opened up to competition for all professional customers. At that date RTE, like all other electricity transmission system operators (TSOs) in the European Union, should be a legally independent body. The new central role of TSOs in Europe: how are electricity transmission system operators in other EU countries organised?

  7. SAVNET. Current developments and results

    International Nuclear Information System (INIS)

    Complete text of publication follows. Important results have been acquired using the measurements of VLF amplitude and phase signals from the South America VLF Network (SAVNET) stations. This network, which is an international project lead by Brazil in cooperation with Peru and Argentina, started operating in April 2006, and now counts on eight stations (Atibaia, Palmas, Santa Maria and Estacao Antarctica Comandante Ferraz in Brazil; Piura, Punta-Lobos and Ica, in Peru; CASLEO, in Argentina). Researches, through the last decades, have been demonstrated the versatility of the VLF technique for many scientific and technological purposes. In this work, we summarize some recent relevant results with SAVNET data bases. Studying the daily C-region post sunrise hump (PSRH) parameter time series, two periods with distinct behavior patterns were observed: one, from March to October, which is characterized by a slow variability well related to the mean solar illumination over the VLF propagation paths; and another period with more variability possibly related to the temperature and Nitric Oxide concentration variations as by space instruments, between October and March. Furthermore, the analysis of phase and amplitude daily variations show seasonal effects which were removed and the remaining signals compared to the incident solar Lyman-α radiation. These results along with future initiatives using SAVNET will be outlined in this presentation.

  8. Presentation of the results 97

    International Nuclear Information System (INIS)

    Gaz de France (GDF) presents in a press kit the main results achieved in 1997. The European community has formulated a project of definition of rules concerning the natural gas market. Minima values for annual consumptions have been defined and the consumption and use of natural gas in EC countries is described. The financial results of GDF in 1997 are compared with previous years. Net sales grew by nearly 1 billion french francs to reach 55 billion. Overall sales were down by 4% but the share of natural gas in french energy consumption increased and sales to industrial users went up in particular due to new cogeneration plants installed in 1996. A comparison of gas prices in Europe is given for the years 1985 to 1998. The efforts of GDF to offer increased quality of services concerning in particular safety aspects as checking programs and installation of new safeguard appliances are described. The efforts of GDF to increase the energy market share of natural gas resulted in the development of new products like cogeneration, air conditioning and fuels for automotive needs. (C.B.)

  9. Results Evaluation in Reduction Rhinoplasty

    Directory of Open Access Journals (Sweden)

    Arima, Lisandra Megumi

    2011-01-01

    Full Text Available Introduction: Final results evaluation after rhinoplasty is a not a topic widely studied from the patient's viewpoint. Objective:Evaluate the satisfaction of the patients submitted to reduction rhinoplasty, from the questionnaire Rhinoplasty Outcomes Evaluation (ROE. Method: Longitudinal study, retrospective cut type, of the preoperative and postoperative satisfaction. The sample was composed by 28 patients who were submitted to rhinoplasty and answered the ROE questionnaire. Three variables were obtained: satisfaction note that the patient had with his/her image before the surgery; note of satisfaction with the current appearance; the difference of the average satisfaction notes between postoperative and preoperative approaches. Results: The postoperative note was higher than the preoperative in all patients. We noticed a difference between the average of the postoperative and preoperative of 48.3 (p75 considered to be an excellent outcome (67.9%. Conclusions: The ROE questionnaire is a helpful tool to show the satisfaction of the patient submitted to reduction rhinoplasty. About 92% of the patients submitted to reduction rhinoplasty consider the postoperative result to be good or excellent.

  10. German experimental programs and results

    International Nuclear Information System (INIS)

    Reactor pressure vessels and piping of the primary circuit form part of the safety research related components in nuclear power plant. The integrity of these components in the presence of defects of limited size has to be guaranteed under both operational and accident loading conditions. In the period from 1973 to today, on the one hand, within the framework of reactor safety research, the Federal Minister for Education, Science, Research and Technology (Bonn) sponsored a series of research projects which are listed and are logically linked to each other. On the other hand the utilities, manufacturers and vendors of nuclear power plants performed series of tests with pipes and components to solve their specific problems. Having regard to the results of the supporting projects the experimental verification of Leak-Before-Break behavior was to be demonstrated, the postulation of fracture preclusion for piping (straight pipe, bends and branches) confirmed and thereby the safety margin against massive failure also quantified. A general overview is given of the types of defects and loadings, and of the main objectives. As the results reveal, they can be called upon for the safety assessment of ferritic and austenitic piping, in the primary and secondary circuits of nuclear power plant. Moreover, because of the great spread of the test parameters, they are also important for the design and assessment of piping in other technical plant. On the strength of the test results, it appears to be justified to rule out catastrophic fractures (2F-fractures) even on pipes of dimensions corresponding to those of a main coolant pipe of a pressurized water reactor plant on the basis of a mechanical deterministic safety analysis in correspondence with the Basis Safety Concept (Principle of Fracture Exclusion)

  11. ISO: highlights of recent results

    Science.gov (United States)

    Metcalfe, L.; Salama, A.

    ESA's Infrared Space Observatory (ISO) mission, operating in the wavelength range from 2.5 to 240 microns, made over 26000 scientific observations during its 2.5 year operational lifetime. ISO's results broke new ground on all scales. New asteroid counts and improved asteroid thermophysical models augmented important advances in Solar System chemistry to comprise a striking body of results addressing our planetary system. In turn, parallels between the chemical composition of Solar System dust and dust around other stars revealed by the comparison of stellar spectra with cometary spectra, together with results on the incidence and stability of stellar disks, recall the birth of our Solar System and point to fundamental similarities with other star systems. Numerous important facts concerning the chemistry of the ISM have unfolded, such as the ubiquity of water and of the probably-organic carriers of the Unidentified Infrared Bands (UIBs). The large systematic body of data on galactic stars has permitted fascinating advances in the characterisation of important aspects of stellar evolution. Investigations of nearby normal galaxies complement template specimens of interacting galaxies. These in turn exemplify galaxy evolutionary processes in the early Universe associated with a huge burst of dust-obscured star formation at redshifts of just below one. This global surge of star formation has vital implications for the interpretation and explanation of major components of the Extragalactic Background Light (EBL) and for charting the global history of star formation and the relative importance of sources which derive their energy from accretion processes. Representative examples of key aspects of ISO's recent scientific output will be presented, once again affirming ISO's place at the forefront of successful space-borne astronomy missions.

  12. Engineering model cryocooler test results

    International Nuclear Information System (INIS)

    This paper reports that recent testing of diaphragm-defined, Stirling-cycle machines and components has demonstrated cooling performance potential, validated the design code, and confirmed several critical operating characteristics. A breadboard cryocooler was rebuilt and tested from cryogenic to near-ambient cold end temperatures. There was a significant increase in capacity at cryogenic temperatures and the performance results compared will with code predictions at all temperatures. Further testing on a breadboard diaphragm compressor validated the calculated requirement for a minimum axial clearance between diaphragms and mating heads

  13. Results from IceCube

    Directory of Open Access Journals (Sweden)

    DeYoung Tyce

    2016-01-01

    Full Text Available Data from the IceCube Neutrino Observatory have revealed the existence of a flux of high energy neutrinos of extraterrestrial origin, which is observed in a number of analyses spanning different energy ranges, fields of view, and neutrino flavors. The current data are consistent with an isotropic, equal-flavor flux described by a simple power law spectrum, but deviations from this simple model cannot yet be constrained with high precision. The existing observations in this area are reviewed, along with recent results on dark matter searches and observations of cosmic rays.

  14. Data bases for LDEF results

    Science.gov (United States)

    Bohnhoff-Hlavacek, Gail

    1993-01-01

    The Long Duration Exposure Facility (LDEF) carried 57 experiments and 10,000 specimens for some 200 LDEF experiment investigators. The external surface of LDEF had a large variety of materials exposed to the space environment which were tested preflight, during flight, and post flight. Thermal blankets, optical materials, thermal control paints, aluminum, and composites are among the materials flown. The investigations have produced an abundance of analysis results. One of the responsibilities of the Boeing Support Contract, Materials and Systems Special Investigation Group, is to collate and compile that information into an organized fashion. The databases developed at Boeing to accomplish this task is described.

  15. First half 2005 financial results

    International Nuclear Information System (INIS)

    With manufacturing facilities in over 40 countries and a sales network in over 100, AREVA offers customers technological solutions for nuclear power generation and electricity transmission and distribution. The group also provides interconnect systems to the telecommunications, computer and automotive markets. This document presents the first half 2005 financial results of the group: 1 - overall performance: sales revenue, operating income, consolidated net income, operating cash flow, balance sheet; 2 - outlook; 3 - performance by business division: front-end division, reactors and services division, back end division, transmission and distribution division, connectors division

  16. Overview of recent ALICE results

    CERN Document Server

    Gunji, Taku

    2016-01-01

    The ALICE experiment explores the properties of strongly interacting QCD matter at extremely high temperatures created in Pb-Pb collisions at LHC and provides further insight into small-system physics in (high-multiplicity) pp and p-Pb collisions. The ALICE collaboration presented 27 parallel talks, 50 posters, and 1 flash talk at Quark Matter 2015 and covered various topics including collective dynamics, correlations and fluctuations, heavy flavors, quarkonia, jets and high $p_{\\rm T}$ hadrons, electromagnetic probes, small system physics, and the upgrade program. This paper highlights some of the selected results.

  17. Recent electroweak results from ATLAS

    CERN Document Server

    Schmitz, Simon; The ATLAS collaboration

    2016-01-01

    Recent measurements and searches in the electroweak sector of the Standard Model by the ATLAS experiment at the LHC are reported. The results are based on $20.3\\,\\rm fb^{-1}$ of proton-proton collisions at $\\sqrt{s}=8\\,\\rm TeV$ for $WW$, $WZ$, $ZZ$, $Z\\gamma$ and $Z\\gamma\\gamma$ production as well as on $3.2\\,\\rm fb^{-1}$ of proton-proton collisions at $\\sqrt{s}=13\\,\\rm TeV$ for $WZ$ and $ZZ$ production.

  18. Latest DVCS Results from HERMES

    CERN Document Server

    Yaschenko, Sergey

    2010-01-01

    Hard exclusive leptoproduction of real photons on nucleons and nuclei, Deeply Virtual Compton Scattering (DVCS), is one of the theoretically cleanest ways to access Generalized Parton Distributions (GPDs). During 1996–2006 the HERMES experiment at DESY, Hamburg, collected data on DVCS utilizing the HERA polarized electron or positron beams with energies of 27.6 GeV, and longitudinally and transversely polarized or unpolarized gas targets (H, D or heavier nuclei). The azimuthal asymmetries measured in the DVCS process allow access to the imaginary and/or real part of certain combinations of GPDs. An overview of the latest HERMES results on DVCS is presented.

  19. RSG Deployment Case Testing Results

    Energy Technology Data Exchange (ETDEWEB)

    Owsley, Stanley L.; Dodson, Michael G.; Hatchell, Brian K.; Seim, Thomas A.; Alexander, David L.; Hawthorne, Woodrow T.

    2005-09-01

    The RSG deployment case design is centered on taking the RSG system and producing a transport case that houses the RSG in a safe and controlled manner for transport. The transport case was driven by two conflicting constraints, first that the case be as light as possible, and second that it meet a stringent list of Military Specified requirements. The design team worked to extract every bit of weight from the design while striving to meet the rigorous Mil-Spec constraints. In the end compromises were made primarily on the specification side to control the overall weight of the transport case. This report outlines the case testing results.

  20. Long Trace Profiler survey results

    International Nuclear Information System (INIS)

    Today the Long Trace Profiler (LTP) is widely accepted as a viable way to measure X-ray mirrors, and at some institutions is the only instrument available for measuring long, high-curvature aspheres. Although some questions of absolute accuracy over the entire LTP measurement range remain unanswered, a comparison of LTPs can still be made to assess measurement variation. Recently a round robin survey of some LTPs within the United States has been made using a single set of mirrors. These mirrors were used to characterize the performance of an LTP over its advertised range of operation. The results of this survey are presented here

  1. Long Trace Profiler survey results

    Energy Technology Data Exchange (ETDEWEB)

    Irick, Steve.

    1999-07-01

    Today the Long Trace Profiler (LTP) is widely accepted as a viable way to measure X-ray mirrors, and at some institutions is the only instrument available for measuring long, high-curvature aspheres. Although some questions of absolute accuracy over the entire LTP measurement range remain unanswered, a comparison of LTPs can still be made to assess measurement variation. Recently a round robin survey of some LTPs within the United States has been made using a single set of mirrors. These mirrors were used to characterize the performance of an LTP over its advertised range of operation. The results of this survey are presented here.

  2. THE ECONOMIC RESULTS OF GLOBALIZATION

    OpenAIRE

    Mustafa Talas; Yaşar Kaya

    2014-01-01

    Globalization is the fact that it is one of the most important issue in the world in recent years. It has shown to us that globalization has got concrete results in economical life. It is possible to tell that this fact is a scroll which effects social and political systems. Globalizatin has been seen that it would have effect on both its follower and its contrary. Besides economy has exhibited the strong direction of globalization. People, culture and economies has connected each other a...

  3. FFTF status and test results

    International Nuclear Information System (INIS)

    A general description of the FFTF is presented concerning the construction progress; status of startup and selected startup test results; and planned experiment program during and subsequent to the startup testing program. The FFTF is a 400 MWt, sodium cooled test reactor plant consisting of a fast-neutron reactor fueled by mixed plutonium oxide-uranium oxide fuel elements, three independent heat transport loops, extensive instrumentation, fuel handling equipment, and auxiliary systems which support the main reactor and cooling systems. The FFTF contains no steam generators, electrical generating equipment, or breeding blankets. Heat generated in the reactor is released to the ambient atmosphere by twelve large sodium-to-air heat exchangers

  4. Results from the NOMAD experiment

    CERN Document Server

    Popov, B A

    2000-01-01

    The NOMAD experiment has sought nu /sub mu / implies/implied by nu /sub tau / oscillations by looking for the emergence of tau /sup -/ in events from the CERN SPS neutrino beam. With some improvements in the techniques of analysis in relation to the results published previously and with the inclusion of data from the 1998 run, no evidence for the oscillations has been found, which results in an updated limit on the oscillation probability [P( nu /sub mu / to nu /sub tau /)<0.5* 10/sup -3/ at a 90% C.L.]. The corresponding limit on the oscillation mixing angle is given by sin/sup 2/2 theta /sub mu tau /<1.0*10/sup -3/ for large Delta m/sup 2/. By using a 1% contamination of nu /sub e/ in the neutrino beam, we can also rule out nu /sub e/ implies/implied by nu /sub tau / oscillations and constrain the probability of the relevant transition as P( nu /sub 3/ to nu /sub tau /)<3*10/sup -2/ at a 90% C.L. (sin/sup 2/2Q/sub e tau /<6*10/sup -2/ at large Delta m/sup 2/). (10 refs).

  5. Unfavourable results following reduction mammoplasty

    Directory of Open Access Journals (Sweden)

    Lakshmi Saleem

    2013-01-01

    Full Text Available Breast reduction is a common cosmetic surgical procedure. It aims not only at bringing down the size of the breast proportionate to the build of the individual, but also to overcome the discomfort caused by massive, ill-shaped and hanging breasts. The operative procedure has evolved from mere reduction of breast mass to enhanced aesthetic appeal with a minimum of scar load. The selection of technique needs to be individualised. Bilateral breast reduction is done most often. Haematoma, seroma, fat necrosis, skin loss, nipple loss and unsightly, painful scars can be the complications of any procedure on the breast. These may result from errors in judgement, wrong surgical plan and imprecise execution of the plan. Though a surfeit of studies are available on breast reduction, very few dwell upon its complications. The following article is a distillation of three decades of experience of the senior author (L.S. in reduction mammoplasty. An effort is made to understand the reasons for unfavourable results. To conclude, most complications can be overcome with proper selection of procedure for the given patient and with gentle tissue handling.

  6. Unfavourable results in thumb reconstruction

    Directory of Open Access Journals (Sweden)

    Samir M Kumta

    2013-01-01

    Full Text Available The history of thumb reconstruction parallels the history of hand surgery. The attributes that make the thumb unique, and that the reconstructive surgeon must assess and try to restore when reconstructing a thumb, are: Position, stability, strength, length, motion, sensibility and appearance. Deficiency in any of these attributes can reduce the utility of the reconstructed thumb. A detailed assessment of the patient and his requirements needs to be performed before embarking on a thumb reconstruction. Most unsatisfactory results can be attributed to wrong choice of procedure. Component defects of the thumb are commonly treated by tissue from adjacent fingers, hand or forearm. With refinements in microsurgery, the foot has become a major source of tissue for component replacement in the thumb. Bone lengthening, osteoplastic reconstruction, pollicisation, and toe to hand transfers are the commonest methods of thumb reconstruction. Unfavourable results can be classified as functional and aesthetic. Some are common to all types of procedures. However each type of reconstruction has its own unique set of problems. Meticulous planning and execution is essential to give an aesthetic and functionally useful thumb. Secondary surgeries like tendon transfers, bone grafting, debulking, arthrodesis, may be required to correct deficiencies in the reconstruction. Attention needs to be paid to the donor site as well.

  7. New results from B physics

    International Nuclear Information System (INIS)

    Recent results are reported on exclusive decays of Β mesons. For the first time the decay B- → D*0 l-ν-bar was analyzed with a full reconstruction of the D*0 meson. The branching ratios of all exclusive semileptonic decays B-bar → D(*)l-ν-bar have been measured, using partial reconstruction of the charmed final state. First evidence was obtained for the exclusive semileptonic b → u decay B- → ρ0 l- ν-bar, with a branching ratio BR(B- → ρ0l-ν-bar) = (1.13 ± 0.36 ± 0.27) . 10-3. The hadronic double charm decays B-bar → D(*)-sD(*) have been observed in all possible eight decay modes, with branching ratios between 1% and 3%. By comparing the inclusive and exclusive results to theoretical predictions, values around 270 MeV are obtained for the weak decay constant fDs. B meson decays into χc mesons have been measured inclusively and in the exclusive channel B- → χclK-. (author)

  8. Heel pain--operative results.

    Science.gov (United States)

    Baxter, D E; Thigpen, C M

    1984-01-01

    In 6 years through 1982, the authors performed 34 operative cases in 26 patients with recalcitrant heel pain. The operative procedure involves an isolated neurolysis of the mixed nerve supplying the abductor digiti quinti muscle as it passes beneath the abductor hallucis muscle and beneath the medial ridge of the calcaneus. The deep fascia of the abductor hallucis muscle is released routinely, and an impinging heel spur or tight plantar fascia is partially removed or released if it is causing entrapment of the nerve. The biomechanical pathogenesis of heel pain in relation to pes planus and pes cavus predisposing to an entrapment neuropathy is described, and the anatomy of the heel in relation to the nerve distribution is clarified and well illustrated. Of the 34 operated heels, 32 had good results and two had poor results. Heel pain can cause total disability in the working population and may jeopardize one's employment or professional athletic career. The authors believe operative treatment has a place in the care of recalcitrant heel pain and that an entrapment neuropathy is an etiological factor in heel pain.

  9. Toxocariasis Resulting in Seeming Allergy

    Directory of Open Access Journals (Sweden)

    Rosanna Qualizza

    2009-09-01

    Full Text Available Toxocara canis is an intestinal nematode affecting dogs and cats that causes human infestations by ingestion of embryonated eggs excreted in dogs' faeces. Humans are transport hosts, in whom the larvae do not develop to adult worms, but may migrate to various tissues and organs, and survive for several years, giving rise to several clinical symptoms, which include allergy-like presentations. We report three cases presenting as dermatitis, rhinitis, asthma, and conjunctivitis which were diagnosed and unsuccessfully treated as allergy. The correct diagnosis was established after detecting anti-Toxocara antibodies by Western blotting. All clinical symptoms showed improvement after starting treatment with mebendazole and subsequent courses of the antiparasitic drug resulted in full recovery. This suggests the possible role of Toxocara canis in inducing chronic symptoms of allergic type. This is particularly important for asthma, where it has been demonstrated that Toxocara canis infection causes allergic inflammation in the lungs associated with bronchial hyperreactivity. On the other hand, in our patients with asthma and with dermatitis the positive results from allergy tests were a confounding factor in delaying the correct diagnosis, which was finally obtained by the detection of antibodies to Toxocara canis.

  10. APS undulator radiation: First results

    International Nuclear Information System (INIS)

    The first undulator radiation has been extracted from the Advanced Photon Source (APS). The results from the characterization of this radiation are very satisfactory. With the undulator set at a gap of 15.8 mm (K=1.61), harmonics as high as the 17th were observed using a crystal spectrometer. The angular distribution of the third-harmonic radiation was measured, and the source was imaged using a zone plate to determine the particle beam emittance. The horizontal beam emittance was found to be 6.9 ± 1.0 nm-rad, and the vertical emittance coupling was found to be less than 3%. The absolute spectral flux was measured over a wide range of photon energies, and it agrees remarkably well with the theoretical calculations based on the measured undulator magnetic field profile and the measured beam emittance. These results indicate that both the emittance of the electron beam and the undulator magnetic field quality exceed the original specifications

  11. [Assessment of bariatric surgery results].

    Science.gov (United States)

    Barros, Lívia Moreira; Frota, Natasha Marques; Moreira, Rosa Aparecida Nogueira; de Araújo, Thiago Moura; Caetano, Joselany Áfio

    2015-03-01

    The objective was to evaluate the results of bariatric surgery in patients in the late postoperative period using the Bariatric Analysis and Reporting Outcome System (BAROS). This cross-sectional study was conducted from November 2011 to June 2012 at a hospital in the state of Ceará, Brazil. Data were collected from 92 patients using the BAROS protocol, which analyzes weight loss, improved comorbidities, complications, reoperations and Quality of Life (QoL). Data were analysed using the chi-squared test, Fischer's exact test and the Mann-Whitney test. There was a reduction in the Body Mass Index (47.2±6.8 kg/m2 in the pre-operatory and 31.3±5.0 kg/m2 after surgery, p<0.001). The comorbidity with the highest resolution was arterial hypertension (p<0.001), and QV improved in 94.6% of patients. The main complications were hair loss, incisional hernia and cholelithiasis. The surgery provided satisfactory weight loss and improvements in the comorbidities associated to a better QL. Use of the BAROS protocol allows nurses to plan interventions and maintain the good results. PMID:26098798

  12. Double Chooz and recent results

    Science.gov (United States)

    Meregaglia, A.; Double Chooz Collaboration

    2016-07-01

    The reactor bar{{ν}}e^{} disappearance experiment Double Chooz, located in France near the power plant of Chooz, has as main goal the measurement of the θ_{{13}}^{} mixing angle. For the first time, in 2011, the experimental results gave an indication for a non-zero value of such an oscillation parameter. The mixing angle was successively measured using only the far detector finding the best fit value of sin2(2 θ_{{13}}^{}) = 0.090+0.033-0.029 . The near detector started data taking in December 2014 and it will allow to reduce the systematic errors so far dominated by the reactor flux uncertainty. In this paper a review of the experiment is presented focusing on the so-called Gadolinium-III results (DOUBLE CHOOZ COLLABORATION (ABE Y. et al.), JHEP, 10 (2014) 086; 02 (2015) 074). Furthermore additional physics measurements are presented such as the capability of Double Chooz to identify the ortho-positronium state on event by event basis.

  13. Altered translation of GATA1 in Diamond-Blackfan anemia

    OpenAIRE

    Ludwig, Leif S.; Gazda, Hanna T.; Eng, Jennifer C.; Eichhorn, Stephen W.; Thiru, Prathapan; Ghazvinian, Roxanne; George, Tracy I.; Gotlib, Jason R.; Beggs, Alan H.; Sieff, Colin A.; Lodish, Harvey F.; Lander, Eric S.; Sankaran, Vijay G

    2014-01-01

    Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA),1,2 congenital asplenia,3 and T-cell leukemia.4 Yet how mutations in such ubiquitously expressed proteins result in cell-type and tissue specific defects remains a mystery.5 Here, we show that GATA1 mutations that reduce full-length protein levels of this critical hematopoietic transcription factor can cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the...

  14. Telomere length is inherited with resetting of the telomere set-point

    OpenAIRE

    Chiang, Y. Jeffrey; Calado, Rodrigo T.; Karen S Hathcock; Lansdorp, Peter M.; Young, Neal S; Richard J Hodes

    2010-01-01

    We have studied models of telomerase haploinsufficiency in humans and mice to analyze regulation of telomere length and the significance of “set points” in inheritance of telomere length. In three families with clinical syndromes associated with short telomeres resulting from haploinsufficient mutations in TERT, the gene encoding telomerase reverse transcriptase, we asked whether restoration of normal genotypes in offspring of affected individuals would elongate inherited short telomeres. Tel...

  15. Results of bentonite grouting experiment

    International Nuclear Information System (INIS)

    The Bentonite grouting, which will not solidify, is mainly expected to reduce the hydraulic conductivity of underground water in the expected damage zone by filling the fractures or cracks, so the evaluation of the degree of hydraulic conductivity, stability and the improvement area becomes important. The study and basic experiments for sealing of the adits have been promoted, up to now, from the aspects of the characteristics and long term stability of candidate materials, and design and construction (Pusch et al., 1987; Tanai and Masuda, 1991). However, in Japan, the application examples of clay type materials for grouting are extremely few and is limited to the construction experience of the national oil underground storage at Kuji (Miyanaga and Ebara, 1993), with the exception of some test cases (Boergesson et al., 1991) from overseas. This report summarize basic characteristics of the clay type material relevant to the hydraulic conductivity, from the result of the clay grouting experiment conducted at the rock site. (author)

  16. Results from ISTC frame work

    Energy Technology Data Exchange (ETDEWEB)

    Fukahori, Tokio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    Under International Science Research Center (ISTC) projects, JAERI Nuclear Data Center has been taking a role of collaborator and monitor for following items; (1) Measurement of the Fission Neutron Spectra of the Minor Actinides and Spontaneous Fission of Curium Isotopes (ISTC no. 183: V.I. Khlopin Radium Institute, KRI, St. Petersburg, Russia), (2) Measurement and Analysis of the Basic Nuclear Data for Minor Actinides (ISTC no. 304: Institute of Physics and Power Engineering, IPPE, Obninsk, Russia), and Evaluation of Actinide Nuclear Data (ISTC no. CIS-3: Radiation Physics and Chemistry Problems Institute, RPCPI, Minsk, Belarus). These are related to the Japanese OMEGA Project and expected to supply minor actinide (MA) nuclear data, since Russia has good quality MA samples, experimental technique and nuclear data evaluation experiences. In this report, out-line and some results of above three projects are reviewed. (author)

  17. Results from the AMANDA detector

    CERN Document Server

    Ackermann, M; Albrecht, H; Bai, X; Bartelt, M; Barwick, S W; Bay, R; Becka, T; Becker, J K; Becker, K H; Bernardini, E; Bertrand, D; Boersma, D J; Boser, S; Botner, O; Bouchta, A; Bouhali, O; Braun, J; Burgess, C; Burgess, T; Castermans, T; Chirkin, D; Collin, B; Conrad, J; Cooley, J; Cowen, D F; Davour, A; De Clercq, C; Pérez de los Heros, C; De Young, T R; Desiati, P; Ekstrom, P; Feser, T; Gaisser, T K; Ganugapati, R; Geenen, H; Gerhardt, L; Goldschmidt, A; Gross, A; Hallgren, A; Halzen, F; Hanson, K; Hardtke, R; Harenberg, T; Hauschildt, T; Helbing, K; Hellwig, M; Herquet, P; Hill, G C; Hodges, J; Hubert, D; Hughey, B; Hulth, P O; Hultqvist, K; Hundertmark, S; Jacobsen, J; Kampert, K H; Karle, A; Kelley, J; Kestel, M; Köpke, L; Kowalski, M; Krasberg, M; Kühn, K; Leich, H; Leuthold, M; Liubarsky, I; Madsen, J; Mandli, K; Marciniewski, P; Martino, J R; Matis, H S; McParland, C P; Messarius, T; Minaeva, Y; Miocinovic, P; Morse, R; Munich, K; Nahnhauer, R; Nam, J W; Neunhoffer, T; Niessen, P; Nygren, D R; Ogelman, H; Olbrechts, P; Pohl, A C; Porrata, R; Price, P B; Przybylski, G T; Rawlins, K; Resconi, E; Rhode, W; Ribordy, M; Richter, S; Sander, H G; Schinarakis, K; Schlenstedt, S; Schneider, D; Schwarz, R; Silvestri, A; Solarz, M; Spiczak, G M; Spiering, C; Stamatikos, M; Steele, D; Steffen, P; Stokstad, R G; Sulanke, K H; Taboada, I; Thollander, L; Tilav, S; Wagner, W; Walck, C; Walter, M; Wang, Y R; Wiebusch, C; Wischnewski, R; Wissing, H; Woschnagg, K; Yodh, G

    2004-01-01

    The Antarctic Muon And Neutrino Detector Array (AMANDA) is a high- energy neutrino telescope based at the geographic south pole. It is a lattice of photomultiplier tubes buried deep in the polar ice, which is used as interaction and detection medium. The primary goal of this detector is the observation of astronomical sources of high-energy neutrinos. This paper shows the latest results of the search for a diffuse flux of extraterrestrial nu /sub mu /s with energies between 10/sup 11/ eV and 10/sup 18/ eV, nu /sub mu /s emitted from point sources and nu /sub mu /s from dark matter annihilation in the Earth and the Sun.

  18. Recent Results from Telescope Array

    CERN Document Server

    Fukushima, M

    2015-01-01

    The Telescope Array (TA) is an experiment to observe Ultra-High Energy Cosmic Rays (UHECRs). TA's recent results, the energy spectrum and anisotropy based on the 6-year surface array data, and the primary composition obtained from the shower maximum Xmax are reported. The spectrum demonstrates a clear dip and cutoff. The shape of the spectrum is well described by the energy loss of extra-galactic protons interacting with the cosmic microwave background (CMB). Above the cutoff, a medium-scale (20 degrees radius) flux enhancement was observed near the Ursa-Major. A chance probability of creating this hotspot from the isotropic flux is 4.0 sigma. The measured Xmax is consistent with the primary being proton or light nuclei for energies 10^18.2 eV - 10^19.2 eV.

  19. Results from KASCADE-Grande

    Energy Technology Data Exchange (ETDEWEB)

    Bertaina, M., E-mail: bertaina@to.infn.it [Dipartimento di Fisica Generale dell' Universita, Torino (Italy); Apel, W.D. [Institut fuer Kernphysik, KIT - Karlsruher Institut fuer Technologie (Germany); Arteaga-Velazquez, J.C. [Universidad Michoacana, Instituto de Fisica y Matematicas, Morelia (Mexico); Bekk, K. [Institut fuer Kernphysik, KIT - Karlsruher Institut fuer Technologie (Germany); Bluemer, J. [Institut fuer Kernphysik, KIT - Karlsruher Institut fuer Technologie (Germany); Institut fuer Experimentelle Kernphysik, KIT - Karlsruher Institut fuer Technologie (Germany); Bozdog, H. [Institut fuer Kernphysik, KIT - Karlsruher Institut fuer Technologie (Germany); Brancus, I.M. [National Institute of Physics and Nuclear Engineering, Bucharest (Romania); Buchholz, P. [Fachbereich Physik, Universitaet Siegen (Germany); Cantoni, E. [Dipartimento di Fisica Generale dell' Universita, Torino (Italy); Istituto di Fisica dello Spazio Interplanetario, INAF Torino (Italy); Chiavassa, A. [Dipartimento di Fisica Generale dell' Universita, Torino (Italy); Cossavella, F. [Institut fuer Experimentelle Kernphysik, KIT - Karlsruher Institut fuer Technologie (Germany); and others

    2012-11-11

    The KASCADE-Grande experiment, located at Karlsruhe Institute of Technology (Germany) is a multi-component extensive air-shower experiment devoted to the study of cosmic rays and their interactions at primary energies 10{sup 14}-10{sup 18} eV. Main goals of the experiment are the measurement of the all-particle energy spectrum and mass composition in the 10{sup 16}-10{sup 18} eV range by sampling charged (N{sub ch}) and muon (N{sub {mu}}) components of the air shower. The method to derive the energy spectrum and its uncertainties, as well as the implications of the obtained result, is discussed. An overview of the analyses performed by KASCADE-Grande to derive the mass composition of the measured high-energy comic rays is presented as well.

  20. Airfreight forecasting methodology and results

    Science.gov (United States)

    1978-01-01

    A series of econometric behavioral equations was developed to explain and forecast the evolution of airfreight traffic demand for the total U.S. domestic airfreight system, the total U.S. international airfreight system, and the total scheduled international cargo traffic carried by the top 44 foreign airlines. The basic explanatory variables used in these macromodels were the real gross national products of the countries involved and a measure of relative transportation costs. The results of the econometric analysis reveal that the models explain more than 99 percent of the historical evolution of freight traffic. The long term traffic forecasts generated with these models are based on scenarios of the likely economic outlook in the United States and 31 major foreign countries.

  1. Latest results from KLOE-2

    Directory of Open Access Journals (Sweden)

    Bloise Caterina

    2014-01-01

    Full Text Available The KLOE experiment at the Frascati φ–factory recently obtained results on i CPT and Lorentz invariance tests from the study of quantum interference of the neutral kaon pairs; ii precision measurement of the branching fraction, BR(K+ → π+π−π+(γ = 0.05565 ± 0.00031stat ± 0.00025syst, and iii on dark photon searches with the analysis of the e+e− → µµγ final state. We have also studied the transition form factors of the φ meson to the pseudoscalars, π0 and η, that is presented in a separate contribution to this volume.

  2. Research Results and Information Update

    Science.gov (United States)

    2011-01-01

    Research Results Monsoon behavior balanced by glaciers Research Discovers Frequent Mutations of Chromatin Significant Progress in Water Photochemistry Research Structural signature in amorphous alloy formation and plastic deformation The neural basis of Drosophila larval light/darkness preference Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity Determination of electron pairing symmetry of iron-based superconductor FeSe Long-Range Topological Order in Metallic Glass Information Update List of Projects Jointly Funded by NSFC and CNRS in 2011 List of Projects Jointly Funded by NSFC and ESRC in 2011 List of Projects Jointly Funded by NSFC and RS in 2011 List of Projects Jointly Funded by NSFC and RSE in 2011 Funding of Major Program Projects in 2010 Funding of Key Program Projects in 2010

  3. First results on fast baking

    Energy Technology Data Exchange (ETDEWEB)

    Visentin, B. [CEA-Saclay, DSM/DAPNIA/SACM - 91191 Gif/Yvette Cedex (France)]. E-mail: bvisentin@cea.fr; Gasser, Y. [CEA-Saclay, DSM/DAPNIA/SACM - 91191 Gif/Yvette Cedex (France); Charrier, J.P. [CEA-Saclay, DSM/DAPNIA/SACM - 91191 Gif/Yvette Cedex (France)

    2006-07-15

    High gradient performances of bulk niobium cavities go through a low-temperature baking during one or two days, the temperature parameter is adjusted in a narrow tuning range around 110 or 120deg, C. With such treatment, the intrinsic quality factor Q{sub 0} is improved at high fields. Assuming the oxygen diffusion is involved in this phenomenon, we have developed the 'fast baking' (145deg, C/3h) as an alternative method. Similar results have been achieved with this method compared to standard baking. Consequently, for the first time, a link between oxygen diffusion and high field Q-slope has been demonstrated. Furthermore, this method open the way to a simpler and better baking procedure for the large-scale cavity production due to:*time reduction and *possibility to combine baking and drying during cavity preparation.

  4. First results on fast baking

    Science.gov (United States)

    Visentin, B.; Gasser, Y.; Charrier, J. P.

    2006-07-01

    High gradient performances of bulk niobium cavities go through a low-temperature baking during one or two days, the temperature parameter is adjusted in a narrow tuning range around 110 or 120 °C. With such treatment, the intrinsic quality factor Q0 is improved at high fields. Assuming the oxygen diffusion is involved in this phenomenon, we have developed the “fast baking” (145 °C/3 h) as an alternative method. Similar results have been achieved with this method compared to standard baking. Consequently, for the first time, a link between oxygen diffusion and high field Q-slope has been demonstrated. Furthermore, this method open the way to a simpler and better baking procedure for the large-scale cavity production due to: time reduction and possibility to combine baking and drying during cavity preparation.

  5. RESULTS OF SUPPLEMENTAL MST STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Peters, T; David Hobbs, D; Samuel Fink, S

    2006-07-24

    The current design of the Salt Waste Processing Facility (SWPF) includes an auxiliary facility, the Actinide Finishing Facility, which provides a second contact of monosodium titanate (MST) to remove soluble actinides and strontium from waste if needed. This treatment will occur after cesium removal by Caustic-Side Solvent Extraction (CSSX). Although the process changes and safety basis implications have not yet been analyzed, provisions also exist to recover the MST from this operation and return to the initial actinide removal step in the SWPF for an additional (third) contact with fresh waste. A U.S. Department of Energy (DOE) request identified the need to study the following issues involving this application of MST: Determine the effect of organics from the solvent extraction (CSSX) process on radionuclide sorption by MST; Determine the efficiency of re-using MST for multiple contacts; and Examine fissile loading on MST under conditions using a waste containing significantly elevated concentrations of plutonium, uranium, neptunium, and strontium. This report describes the results of three experimental studies conducted to address these needs: (1) Addition of high concentrations of entrained CSSX solvent had no noticeable effect, over a two week period, on the sorption of the actinides and strontium by MST in a direct comparison experiment. (2) Test results show that MST still retains appreciable capacity after being used once. For instance, reused MST--in the presence of entrained solvent--continued to sorb actinides and strontium. (3) A single batch of MST was used to sequentially contact five volumes of a simulant solution containing elevated concentrations of the radionuclides of interest. After the five contacts, we measured the following solution actinide loadings on the MST: plutonium: 0.884 {+-} 0.00539 wt % or (1.02 {+-} 0.0112) E+04 {micro}g/g MST, uranium: 12.1 {+-} 0.786 wt % or (1.40 {+-} 0.104) E+05 {micro}g/g MST, and neptunium: 0.426 {+-} 0

  6. Recent results from dispersant testing

    Energy Technology Data Exchange (ETDEWEB)

    Fingas, M.; Fieldhouse, B.; Wang, Z.; Sigouin, L.; Landriault, M. [Environment Canada, Ottawa, ON (Canada). Emergencies Science Div; Mullin, J.V. [Department of the Interior, Herndon, VA (United States). Minerals Management Service

    2000-07-01

    A number of small studies were conducted at Environment Canada on the topic of dispersants and their effectiveness. Dispersant analytical procedures were reviewed and modified when necessary. Testing of new products was also performed along with the testing of long-term stored dispersants. A comparative evaluation of Corexit 9500 and 9527 dispersant formulations showed major modifications to the quantity of dispersed oil, although the Swirling Flask Test did not undergo major modifications. This method used to rely on colorimetric analysis, but was upgraded to gas chromatographic analysis. This move from one method to the other brought on additional changes that had not been considered when the initial change in method was made. Some aspects of the analysis were then improved and corrected to rectify small deficiencies. The authors reported on the results concerning the testing of several new dispersants products. The comparative study between the formulations of Corexit 9500 and 9527 indicated that the effectiveness of 9500 was greater than 9527, but showed no relation to the amount of effectiveness. In terms of statistics, 9527 proved to be more effective than 9500, 25 per cent of the time. The test series conducted on Corexit 9527, stored 20 years in the tank of a truck, varied in effectiveness, toxicity, and colour but did not affect significantly the overall effectiveness of the product in the field. 10 refs., 4 tabs., 2 figs., 1 append.

  7. Recent QCD results from ATLAS

    CERN Document Server

    Pleskot, Vojtech; The ATLAS collaboration

    2016-01-01

    ATLAS has has performed several measurements of phenomena connected to QCD at soft scales or at the transition to the hard regime. These include the measurements at different centre-of-mass energies in Run-1 and Run-2 of the elastic, inelastic and total cross sections in pp collisions, the properties of minimum bias and the underlying event interactions, particle production and their correlations, as well as of diffractive and exclusive events. These results are sensitive to non-perturbative models of soft QCD. Jet and photon production cross sections have been measured differentially for inclusive and multi-object final states at 7, 8 and 13 TeV pp collisions with the ATLAS detector and are compared to expectations based on next-to-leading order QCD calculations as well as Monte Carlo simulations. Further studies of jet production properties include the measurements of jet properties, and the determination of the strong coupling constant alpha_s. These measurements provide direct probes of short-distance phy...

  8. Excellent results for CERN runners

    CERN Multimedia

    Hervé Cornet, CERN Running club

    2015-01-01

    As in previous years, thirty or so runners from CERN took part in the Tour du Canton de Genève (more information here, in French only).   The men’s team that won the corporate challenge prize in the Tour du Canton de Genève: (standing, left to right) Patrick Villeton, Phil Hebda, Mika Vesterinen, Steffen Doebert; (sitting, left to right) Guillaume Michet and Camille Ruiz-Llamas. The Laboratory was represented in the corporate challenge by five teams, one of which came first in the men’s category. CERN’s other teams also put in good performances, with one finishing fourth in the men's category and another seventh in the mixed category. Runners from CERN did well in the individual classifications too. All the results can be found here. The Maxi Race team: (left to right) Sebastien Ponce, Alain Cauphy, Klaus Hanke and Christophe Biot. Elsewhere, four CERN runners competed in the finals of the Annecy Maxi Race (site in French only...

  9. Results from the NEXT prototypes

    CERN Document Server

    Oliveira, C A B

    2013-01-01

    NEXT-100 is an electroluminescent high pressure Time Projection Chamber currently under construction. It will search for the neutrino-less double beta decay in 136Xe at the Canfranc Underground Laboratory. NEXT-100 aims to achieve nearly intrinsic energy resolution and to highly suppress background events by taking advantage of the unique properties of xenon in the gaseous phase as the detection medium. In order to prove the principle of operation and to study which are the best operational conditions, two prototypes were constructed: NEXT-DEMO and NEXT-DBDM. In this paper we present the latest results from both prototypes. We report the improvement in terms of light collection (?~3x?) achieved by coating the walls of NEXT-DEMO with tetraphenyl butadiene (TPB), the outstanding energy resolution of 1 % (Full Width Half Maximum) from NEXT-DBDM as well as the tracking capabilities of this prototype (2.1 mm RMS error for point-like depositions) achieved by using a square array of 8x8 SiPMs.

  10. Results from the NEXT prototypes

    Science.gov (United States)

    Oliveira, C. A. B.; NEXT Collaboration

    2013-10-01

    NEXT-100 is an electroluminescent high pressure Time Projection Chamber currently under construction. It will search for the neutrino-less double beta decay in 136Xe at the Canfranc Underground Laboratory. NEXT-100 aims to achieve nearly intrinsic energy resolution and to highly suppress background events by taking advantage of the unique properties of xenon in the gaseous phase as the detection medium. In order to prove the principle of operation and to study which are the best operational conditions, two prototypes were constructed: NEXT-DEMO and NEXT-DBDM. In this paper we present the latest results from both prototypes. We report the improvement in terms of light collection (~ 3×) achieved by coating the walls of NEXT-DEMO with tetraphenyl butadiene (TPB), the outstanding energy resolution of 1 % (Full Width Half Maximum) from NEXT-DBDM as well as the tracking capabilities of this prototype (2.1 mm RMS error for point-like depositions) achieved by using a square array of 8 × 8 SiPMs.

  11. EUPORIAS: plans and preliminary results

    Science.gov (United States)

    Buontempo, C.

    2013-12-01

    Recent advances in our understanding and ability to forecast climate variability have meant that skilful predictions are beginning to be routinely made on seasonal to decadal (s2d) timescales. Such forecasts have the potential to be of great value to a wide range of decision-making, where outcomes are strongly influenced by variations in the climate. In 2012 the European Commission funded EUPORIAS, a four year long project to develop prototype end-to-end climate impact prediction services operating on a seasonal to decadal timescale, and assess their value in informing decision-making. EUPORIAS commenced on 1 November 2012, coordinated by the UK Met Office leading a consortium of 24 organisations representing world-class European climate research and climate service centres, expertise in impacts assessments and seasonal predictions, two United Nations agencies, specialists in new media, and commercial companies in climate-vulnerable sectors such as energy, water and tourism. The poster describes the setup of the project, its main outcome and some of the very preliminary results.

  12. LSND results and their implications

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, D.O. [California Univ., Santa Barbara, CA (United States). Dept. of Physics

    1996-11-01

    The combined 1993, 1994, and 1995 data from the LSND experiment shows a statistically compelling excess of events of the type expected for {nu}{sub {mu}} {yields}{nu}{sub e} neutrino oscillations. An electron between 36 and 60 MeV is identified by Cherenkov and scintillation light from {nu}{sub e}p{yields}e{sup +}n, and if a {gamma} is tightly constrained to be correlated with it from np{yields}d{gamma} (2.2 MeV), then 22 such events are observed, but only 4.6{+-}0.6 are expected from background. The probability that this is a fluctuation is <10{sup -7}. If subsequent analysis shows a similar effect from the independent channel {nu}{sub {mu}}{yields}{nu}{sub e}, then this would imply a neutrino mass difference which would contribute significantly to the dark matter of the universe. Explaining also the solar and atmospheric neutrino deficits results in a neutrino mass pattern which gives a cold + hot dark matter which fits the structure of the universe on all scales and requires a critical density universe and an universe age compatible with that of the oldest stars. This mass pattern involves a sterile neutrino, evidence for which may come from the need for it in producing heavy elements by supernovae and for blowing off the supernova mantle. (author) 3 figs., 18 refs.

  13. Visible Nulling Coronagraph Testbed Results

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Melnick, Gary; Tolls, Volker; Woodruff, Robert; Vasudevan, Gopal; Rizzo, Maxime; Thompson, Patrick

    2009-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a NASA Astrophysics Strategic Mission Concept study and a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC would provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 5-year mission lifetime. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables starlight suppression in broadband light from 480-960 nm. To demonstrate the VNC approach and advance it's technology readiness we have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed.

  14. Results of the 2009 elections

    CERN Multimedia

    Association du personnel

    The elections to renew the Staff Council for the 2010-2011 period are now behind us and we are very pleased to have had at least as many candidates as posts in five of the six electoral colleges. Furthermore, the average rate of participation of 56.8% in these elections is a very good result compared to previous years. We thank the candidates who have committed themselves to actively defending the interests of the staff, and all our members have shown, by voting, their full support of the candidates in their college and Department. This newly-elected Staff Council (see its composition on the following page) will therefore be truly representative of all the sectors and professions of the Organization, which will be a major asset when the Staff Association representatives begin discussions with the Management and Member States in 2010 on the key issues of the five-yearly review and the measures to be taken to absorb the deficit of our Pension Fund. Armed with this vote of confidence, we know that we can count o...

  15. Experimental results of helicon sources

    Institute of Scientific and Technical Information of China (English)

    MIAO Ting-Ting; SHANG Yong; LIU Zhan-Wen; ZHAO Hong-Wei; SUN Liang-Ting; ZHANG Xue-Zhen; ZHAO Huan-Yu; WANG Hui; MA Bao-Hua; LI Xi-Xia; ZHU Yu-Hua; FENG Yu-Cheng; LI Jing-Yu

    2009-01-01

    Helicon plasma sources are known as efficient generators of uniform and high density plasma.A helicon plasma source was developed for the investigation of plasma stripping and plasma lenses at the Institute of Modern Physics, CAS.In this paper, the characteristics of helicon plasma have been studied by using a Langmuir four-probe and a high plasma density up to 3.9×10~(13)/cm~3 has been achieved with the Nagoya type Ⅲ antenna.In the experiment, several important phenomena were found: (1) for a given magnetic induction intensity, the plasma density became greater with the increase of RF power; (2) helicon mode appeared at RF power between 300 W and 400 W; (3) the plasma density gradually tended to saturation as the RF power increased to the higher power; (4) a higher plasma density can be obtained by a good match between the RF power and the magnetic field distribution.The key issue is how to optimize the matching between the RF power and the magnetic field.Moreover, some tests on the extraction of ion beams were performed, and preliminary results are given.The problems which existed in the helicon ion source will be discussed and the increase in beam density will be expected by extraction system optimum.

  16. Theoretical Results on FIEGARCH Processes

    CERN Document Server

    Lopes, Sílvia R C

    2012-01-01

    Here we present a theoretical study on the main properties of FIEGARCH processes. We analyze the conditions for the existence, the invertibility, the stationarity and the ergodicity of these processes. We prove that, if $\\{X_t\\}_{t \\in \\mathds{Z}}$ is a FIEGARCH$(p,d,q)$ process then, under mild conditions, $\\{\\ln(X_t^2)\\}_{t \\in \\mathds{Z}}$ is an ARFIMA$(q,d,0)$ process. The convergence order for the polynomial coefficients that describes the volatility is presented and results related to the spectral representation and to the covariance structure of both processes $\\{\\ln(X_t^2)\\}_{t \\in \\mathds{Z}}$ and $\\{\\ln(\\sigma_t^2)\\}_{t \\in \\mathds{Z}}$ are also discussed. Expressions for the kurtosis and the asymmetry measures for any stationary FIEGARCH$(p,d,q)$ process are also derived. The $h$-step ahead forecast for the processes $\\{X_t\\}_{t \\in \\mathds{Z}}$, $\\{\\ln(\\sigma_t^2)\\}_{t \\in \\mathds{Z}}$ and $\\{\\ln(X_t^2)\\}_{t \\in \\mathds{Z}}$ are given with their respective mean square error forecast. The work also...

  17. Evaluating the RELM Test Results

    Directory of Open Access Journals (Sweden)

    Michael K. Sachs

    2012-01-01

    Full Text Available We consider implications of the Regional Earthquake Likelihood Models (RELM test results with regard to earthquake forecasting. Prospective forecasts were solicited for M≥4.95 earthquakes in California during the period 2006–2010. During this period 31 earthquakes occurred in the test region with M≥4.95. We consider five forecasts that were submitted for the test. We compare the forecasts utilizing forecast verification methodology developed in the atmospheric sciences, specifically for tornadoes. We utilize a “skill score” based on the forecast scores λfi of occurrence of the test earthquakes. A perfect forecast would have λfi=1, and a random (no skill forecast would have λfi=2.86×10-3. The best forecasts (largest value of λfi for the 31 earthquakes had values of λfi=1.24×10-1 to λfi=5.49×10-3. The best mean forecast for all earthquakes was λ̅f=2.84×10-2. The best forecasts are about an order of magnitude better than random forecasts. We discuss the earthquakes, the forecasts, and alternative methods of evaluation of the performance of RELM forecasts. We also discuss the relative merits of alarm-based versus probability-based forecasts.

  18. Preliminary results of ANAIS-25

    CERN Document Server

    Amaré, J; Cuesta, C; García, E; Ginestra, C; Martínez, M; Oliván, M A; Ortigoza, Y; de Solórzano, A Ortiz; Pobes, C; Puimedón, J; Sarsa, M L; Villar, P; Villar, J A

    2013-01-01

    The ANAIS (Annual Modulation with NaI(Tl) Scintillators) experiment aims at the confirmation of the DAMA/LIBRA signal using the same target and technique at the Canfranc Underground Laboratory. 250 kg of ultrapure NaI(Tl) crystals will be used as a target, divided into 20 modules, each coupled to two photomultipliers. Two NaI(Tl) crystals of 12.5 kg each, grown by Alpha Spectra from a powder having a potassium level under the limit of our analytical techniques, form the ANAIS-25 set-up. The background contributions are being carefully studied and preliminary results are presented: their natural potassium content in the bulk has been quantified, as well as the uranium and thorium radioactive chains presence in the bulk through the discrimination of the corresponding alpha events by PSA, and due to the fast commissioning, the contribution from cosmogenic activated isotopes is clearly identified and their decay observed along the first months of data taking. Following the procedures established with ANAIS-0 and ...

  19. Preliminary results of ANAIS-25

    Science.gov (United States)

    Amaré, J.; Cebrián, S.; Cuesta, C.; García, E.; Ginestra, C.; Martínez, M.; Oliván, M. A.; Ortigoza, Y.; Ortiz de Solórzano, A.; Pobes, C.; Puimedón, J.; Sarsa, M. L.; Villar, J. A.; Villar, P.

    2014-04-01

    The ANAIS (Annual Modulation with NaI(Tl) Scintillators) experiment aims at the confirmation of the DAMA/LIBRA signal using the same target and technique at the Canfranc Underground Laboratory. 250 kg of ultrapure NaI(Tl) crystals will be used as a target, divided into 20 modules, each coupled to two photomultipliers. Two NaI(Tl) crystals of 12.5 kg each, grown by Alpha Spectra from a powder having a potassium level under the limit of our analytical techniques, form the ANAIS-25 set-up. The background contributions are being carefully studied and preliminary results are presented: their natural potassium content in the bulk has been quantified, as well as the uranium and thorium radioactive chains presence in the bulk through the discrimination of the corresponding alpha events by PSA, and due to the fast commissioning, the contribution from cosmogenic activated isotopes is clearly identified and their decay observed along the first months of data taking. Following the procedures established with ANAIS-0 and previous prototypes, bulk NaI(Tl) scintillation events selection and light collection efficiency have been also studied in ANAIS-25.

  20. Overview of recent HERMES results

    Science.gov (United States)

    Marukyan, Hrachya

    2016-02-01

    An overview of more recent and important results from the HERMES experiment are presented in this paper. HERMES collected a wealth of data using the 27.6 GeV polarized HERA lepton beam and various polarized and unpolarized gaseous targets. This unique data set opens the door to the measurements of observables sensitive to the multidimensional structure of the nucleon. Among them are semi-inclusive deep-inelastic scattering measurements of azimuthal modulations sensitive to the transverse momentum distributions, such as the leading- twist Sivers and Collins distributions and distributions sensitive to the convolutions of the twist-2 and twist-3 functions. They all provide an information on the three-momentum-dependent quark distributions. Knowledge on the quark distribution as a function of longitudinal momentum and transverse position in impact-parameter space can be accessed, e.g., through exclusive ω—meson leptoproduction, particularly through the measurement of spin density matrix elements and the measurement of azimuthal modulations on transversely polarized proton target. The measurement of Bose-Einstein correlations of hadron pairs in quasi-real leptoproduction are also presented. The transverse polarization of Λ hyperons measured again in quasi-real leptoproduction regime are presented as well. Finally, the new analysis for the search on pentaquark at HERMES are mentioned.

  1. Results from bar pp colliders

    International Nuclear Information System (INIS)

    Recent results bar pp colliders are presented. From elastic scattering experiments at the Tevatron, an average value of σtot = 72.1±2 mb is reported, along with a new measurement of ρ = 0.13 ± 0.7. New measurements of jet direct photon and high pt W and Z production are compared to more precise, higher order predictions from perturbative QCD. Recently available data on the W mass and width give combined values for MW = 80.14±0.27 GeV/c2, and Γ(W) =2. 14 ± 0.08 GeV. From electroweak radiative corrections and MW, one finds Mtop = 130±40 GeV/c2, with a 95% C.L. upper limit at 210 GeV/c2. Current limits on Mtop are presented, along with a review of the prospects for top discovery. From jet data there is no evidence of quark substructure down to the distance scale of 1.4 x 10-17 cm, nor is there evidence for supersymmetry or heavy gauge bosons at bar pp colliders, allowing lower limits on MW, > 520 GeV/c2 and MZ 412 GeV/c2. 66 refs., 26 figs

  2. CALICE results and future plans

    International Nuclear Information System (INIS)

    The CALICE Collaboration is carrying out R for a highly granular calorimeter system, optimised for particle flow calorimetry at a future linear collider. Starting in 2006, a complete calorimeter chain (ECAL, HCAL and tail catcher) has been tested in muon, electron and hadron beams at CERN and Fermilab. Two electromagnetic calorimeters were tested, both based on tungsten absorber - one using ∼10000 1x1 cm2 silicon diode pads as the sensitive medium, and the other using small (1x4 cm2) scintillator strips. The hadron calorimeter had an iron-scintillator sandwich structure, using ∼10000 scintillator tiles read out using silicon photomultipliers (SiPMs). We report here on the analysis of shower data, and the comparison of the results with GEANT4 simulations. Muons are used to calibrate all the detectors, and the study of the response to electrons is a crucial first step in the understanding of all the detectors. One of the main objectives of the analysis is the study of the hadron response, since this can be more difficulty to simulate reliably. Amongst the topics discussed will be the energy response of the system to hadrons, and the use of techniques of software compensation to improve the energy resolution. The high granularity of the calorimeters permit the comparison between data and simulations in unprecedented resolution; for example, individual tracks within the shower can be reconstructed, the start of the shower can be identified with high precision, and the longitudinal and transverse distributions of energy studied. These measurements provide interesting new ways of assessing the accuracy of the various physics models available in GEANT4. We also use the data to test features of the showers which are important for particle flow algorithms. Much of the current work is now directed towards second generation prototypes in which more realistic mechanical designs and readout systems are employed. In 2010-11 a cubic prototype of a digital HCAL based on RPCs

  3. Public Administration reforms and results

    Directory of Open Access Journals (Sweden)

    Gunnar Helgi Kristinsson

    2014-12-01

    Full Text Available Research on administrative reforms during the past thirty years indicates that reform efforts of countries differ. The Anglo Saxon states were at the forefront of the New Public Management movement while countries on mainland Europe were more hesitant and moved further towards the Neo-Weberian state. Academics have tried to explain different reform efforts within countries by looking at political, historical and cultural issues, values and economic factors to name just a few. Three hypotheses are put forward to explain reform efforts in different states. This research involves analysing the implementation of two different reform trends, New Public Management and the Neo-Weberian tradition. The analysis indicates that countries vary in their commitment to reform rather than in the emphasis on either New Public Management or the Neo-Weberian State. Decentralization, clear objectives and consultation with communities and experts are closely related to national reform efforts. However, Iceland does distinguish itself from Europe and the Nordic countries. The analysis reveals that although decentralization is high in the Icelandic system, autonomy of agencies does not have a strong relation to a varied use of administrative instruments. The second part of the article focuses on the results and achievements of reform programmes. The achievement of reform programmes are examined in relation to theories of bounded rationality, street level bureaucracy (bottom up and consensus decision making. Three hypotheses are presented and tested to explain what causes reforms programmes to be successful in some countries and not in others. The analysis reveals that countries are more likely to succeed if bounded rationality is applied with careful preparation and when stakeholders are consulted.

  4. NCV Flow Diagnostic Test Results

    Science.gov (United States)

    Cappuccio, Mina

    1999-01-01

    There were two objectives for this test. First, was to assess the reasons why there is approximately 1.5 drag counts (cts) discrepancy between measured and computed drag improvement of the Non-linear Cruise Validation (NCV) over the Technology Concept Airplane (TCA) wing body (WB) configurations. The Navier-Stokes (N-S) pre-test predictions from Boeing Commercial Airplane Group (BCAG) show 4.5 drag cts of improvement for NCV over TCA at a lift coefficient (CL) of 0. I at Mach 2.4. The pre-test predictions from Boeing Phantom Works - Long Beach, BPW-LB, show 3.75 drag cts of improvement. BCAG used OVERFLOW and BPW-LB used CFL3D. The first test entry to validate the improvement was held at the NASA Langley Research Center (LARC) UPV;T, test number 1687. The experimental results showed that the drag improvement was only 2.6 cts, not accounting for laminar run and trip drag. This is approximately 1.5 cts less than predicted computationally. In addition to the low Reynolds Number (RN) test, there was a high RN test in the Boeing Supersonic Wind Tunnel (BSWT) of NCV and TCA. BSV@T test 647 showed that the drag improvement of NCV over TCA was also 2.6 cts, but this did account for laminar run and trip drag. Every effort needed to be done to assess if the improvement measured in LaRC UPWT and BSWT was correct. The second objective, once the first objective was met, was to assess the performance increment of NCV over TCA accounting for the associated laminar run and trip drag corrections in LaRC UPWT. We know that the configurations tested have laminar flow on portions of the wing and have trip drag due to the mechanisms used to force the flow to go from laminar to turbulent aft of the transition location.

  5. Our Results in Penile Fractures

    Directory of Open Access Journals (Sweden)

    Tufan Süelözgen

    2016-06-01

    Full Text Available Introduction Penile fracture is a urological emergency caused by direct trauma to an erected penis, tearing the tunica albuginea in the corpus cavernosum. The preferred treatment method is draining the hematoma and surgical repair of tunica albuginea tear as soon as possible following diagnosis. Materials and Methods Forty-nine patients who were diagnosed with penile fracture between January 2009 and December 2014 were reviewed. Physical examination was performed to see the extent of penile hematoma, the side of the penile curvature and the presence of blood in the external meatus. Two patients who were diagnosed with urethrorrhagia underwent retrograde urethrogram for urethral injury. In all patients, penile skin was peeled using a circular subcoronal degloving incision and tunica tear was repaired using absorbable suture materials. The patients were then followed for painful erections, penile deformities and erection angles. Results The average age of the 49 patients, who were included in the study, was 36.5 years (21-65. In their etiological questioning, most patients reported the fracture occurring during sexual intercourse. Retrograde urethrography was indicated in 2 patients with blood in the external meatus and were diagnosed with urethral injury. The patients were taken to emergency surgery. Tunica defects varied between 1 and 2 cm. Incomplete urethral injuries were primarily repaired around 18 French Foley catheter. None of the patients reported penile deformity or painful erections. Their erection angles were found to be within the normal range. Conclusion Even though it is a relatively rare condition, penile fractures are so important that might cause serious complications when not treated surgically. A thorough anamnesis and physical examination suffice for diagnosis.

  6. Corral Monitoring System assessment results

    International Nuclear Information System (INIS)

    This report describes the results of a functional and operational assessment of the Corral Monitoring Systems (CMS), which was designed to detect and document accountable items entering or leaving a monitored site. Its development was motivated by the possibility that multiple sites in the nuclear weapons states of the former Soviet Union might be opened to such monitoring under the provisions of the Strategic Arms Reduction Treaty. The assessment was performed at three levels. One level evaluated how well the planned approach addressed the target application, and which involved tracking sensitive items moving into and around a site being monitored as part of an international treaty or other agreement. The second level examined the overall design and development approach, while the third focused on individual subsystems within the total package. Unfortunately, the system was delivered as disassembled parts and pieces, with very poor documentation. Thus, the assessment was based on fragmentary operating data coupled with an analysis of what documents were provided with the system. The system design seemed to be a reasonable match to the requirements of the target application; however, important questions about site manning and top level administrative control were left unanswered. Four weaknesses in the overall design and development approach were detected: (1) poor configuration control and management, (2) inadequate adherence to a well defined architectural standard, (3) no apparent provision for improving top level error tolerance, and (4) weaknesses in the object oriented programming approach. The individual subsystems were found to offer few features or capabilities that were new or unique, even at the conceptual level. The CMS might possibly have offered a unique combination of features, but this level of integration was never realized, and it had no unique capabilities that could be readily extracted for use in another system

  7. Overview of ASDEX Upgrade results

    Science.gov (United States)

    Zohm, H.; Angioni, C.; Arslanbekov, R.; Atanasiu, C.; Becker, G.; Becker, W.; Behler, K.; Behringer, K.; Bergmann, A.; Bilato, R.; Bobkov, V.; Bolshukhin, D.; Bolzonella, T.; Borrass, K.; Brambilla, M.; Braun, F.; Buhler, A.; Carlson, A.; Conway, G. D.; Coster, D. P.; Drube, R.; Dux, R.; Egorov, S.; Eich, T.; Engelhardt, K.; Fahrbach, H.-U.; Fantz, U.; Faugel, H.; Finken, K. H.; Foley, M.; Franzen, P.; Fuchs, J. C.; Gafert, J.; Fournier, K. B.; Gantenbein, G.; Gehre, O.; Geier, A.; Gernhardt, J.; Goodman, T.; Gruber, O.; Gude, A.; Günter, S.; Haas, G.; Hartmann, D.; Heger, B.; Heinemann, B.; Herrmann, A.; Hobirk, J.; Hofmeister, F.; Hohenöcker, H.; Horton, L. D.; Igochine, V.; Jacchia, A.; Jakobi, M.; Jenko, F.; Kallenbach, A.; Kardaun, O.; Kaufmann, M.; Keller, A.; Kendl, A.; Kim, J.-W.; Kirov, K.; Kochergov, R.; Kollotzek, H.; Kraus, W.; Krieger, K.; Kurki-Suonio, T.; Kurzan, B.; Lang, P. T.; Lasnier, C.; Lauber, P.; Laux, M.; Leonard, A. W.; Leuterer, F.; Lohs, A.; Lorenz, A.; Lorenzini, R.; Maggi, C.; Maier, H.; Mank, K.; Manso, M.-E.; Mantica, P.; Maraschek, M.; Martines, E.; Mast, K.-F.; McCarthy, P.; Meisel, D.; Meister, H.; Meo, F.; Merkel, P.; Merkel, R.; Merkl, D.; Mertens, V.; Monaco, F.; Mück, A.; Müller, H. W.; Münich, M.; Murmann, H.; Na, Y.-S.; Neu, G.; Neu, R.; Neuhauser, J.; Nguyen, F.; Nishijima, D.; Nishimura, Y.; Noterdaeme, J.-M.; Nunes, I.; Pautasso, G.; Peeters, A. G.; Pereverzev, G.; Pinches, S. D.; Poli, E.; Proschek, M.; Pugno, R.; Quigley, E.; Raupp, G.; Reich, M.; Ribeiro, T.; Riedl, R.; Rohde, V.; Roth, J.; Ryter, F.; Saarelma, S.; Sandmann, W.; Savtchkov, A.; Sauter, O.; Schade, S.; Schilling, H.-B.; Schneider, W.; Schramm, G.; Schwarz, E.; Schweinzer, J.; Schweizer, S.; Scott, B. D.; Seidel, U.; Serra, F.; Sesnic, S.; Sihler, C.; Silva, A.; Sips, A. C. C.; Speth, E.; Stäbler, A.; Steuer, K.-H.; Stober, J.; Streibl, B.; Strumberger, E.; Suttrop, W.; Tabasso, A.; Tanga, A.; Tardini, G.; Tichmann, C.; Treutterer, W.; Troppmann, M.; Urano, H.; Varela, P.; Vollmer, O.; Wagner, D.; Wenzel, U.; Wesner, F.; Westerhof, E.; Wolf, R.; Wolfrum, E.; Würsching, E.; Yoon, S.-W.; Yu, Q.; Zasche, D.; Zehetbauer, T.; Zehrfeld, H.-P.

    2003-12-01

    Recent results from the ASDEX Upgrade experimental campaigns 2001 and 2002 are presented. An improved understanding of energy and particle transport emerges in terms of a 'critical gradient' model for the temperature gradients. Coupling this to particle diffusion explains most of the observed behaviour of the density profiles, in particular, the finding that strong central heating reduces the tendency for density profile peaking. Internal transport barriers (ITBs) with electron and ion temperatures in excess of 20 keV (but not simultaneously) have been achieved. By shaping the plasma, a regime with small type II edge localized modes (ELMs) has been established. Here, the maximum power deposited on the target plates was greatly reduced at constant average power. Also, an increase of the ELM frequency by injection of shallow pellets was demonstrated. ELM free operation is possible in the quiescent H-mode regime previously found in DIII-D which has also been established on ASDEX Upgrade. Regarding stability, a regime with benign neoclassical tearing modes (NTMs) was found. During electron cyclotron current drive (ECCD) stabilization of NTMs, bgrN could be increased well above the usual onset level without a reappearance of the NTM. Electron cyclotron resonance heating and ECCD have also been used to control the sawtooth repetition frequency at a moderate fraction of the total heating power. The inner wall of the ASDEX Upgrade vessel has increasingly been covered with tungsten without causing detrimental effects on the plasma performance. Regarding scenario integration, a scenario with a large fraction of noninductively driven current (geq50%), but without ITB has been established. It combines improved confinement (tgrE/tgrITER98 ap 1.2) and stability (bgrN les 3.5) at high Greenwald fraction (ne/nGW ap 0.85) in steady state and with type II ELMy edge and would offer the possibility for long pulses with high fusion power at reduced current in ITER.

  8. Corral Monitoring System assessment results

    Energy Technology Data Exchange (ETDEWEB)

    Filby, E.E.; Haskel, K.J.

    1998-03-01

    This report describes the results of a functional and operational assessment of the Corral Monitoring Systems (CMS), which was designed to detect and document accountable items entering or leaving a monitored site. Its development was motivated by the possibility that multiple sites in the nuclear weapons states of the former Soviet Union might be opened to such monitoring under the provisions of the Strategic Arms Reduction Treaty. The assessment was performed at three levels. One level evaluated how well the planned approach addressed the target application, and which involved tracking sensitive items moving into and around a site being monitored as part of an international treaty or other agreement. The second level examined the overall design and development approach, while the third focused on individual subsystems within the total package. Unfortunately, the system was delivered as disassembled parts and pieces, with very poor documentation. Thus, the assessment was based on fragmentary operating data coupled with an analysis of what documents were provided with the system. The system design seemed to be a reasonable match to the requirements of the target application; however, important questions about site manning and top level administrative control were left unanswered. Four weaknesses in the overall design and development approach were detected: (1) poor configuration control and management, (2) inadequate adherence to a well defined architectural standard, (3) no apparent provision for improving top level error tolerance, and (4) weaknesses in the object oriented programming approach. The individual subsystems were found to offer few features or capabilities that were new or unique, even at the conceptual level. The CMS might possibly have offered a unique combination of features, but this level of integration was never realized, and it had no unique capabilities that could be readily extracted for use in another system.

  9. Recent Results on Singularity Strengths

    Science.gov (United States)

    Nolan, Brien

    2002-12-01

    In this contribution, we review some recent results on strengths of singularities. In a space-time (M,g), let γ[τ0, 0) → M be an incomplete, inextendible causal geodesic, affinely parametrised by τ, tangent ěc k. Let Jτ1 :=set of Jacobi fields along γ, orthogonal to γ and vanishing at time τ1 ≥ τ0 i.e. ěc ξ ∈ J{τ 1 } iff D2ξa = -Rbcdakbkdξc, gabξakb = 0, and ěc ξ (τ 1 ) = 0. Vτ1(τ) := volume element defined by full set of independent elements of Jτ1 (2-dim for null geodesies, 3-dim for time-like); Vτ1 := ∥Vτ1∥. Definition (Tipler 1977): γ terminates in a gravitationally strong singularity if for all 0 > τ1 ≥ τ0, lim infτ→0- Vτ1(τ) = 0. γ... gravitationally weak ... lim infτ→0- Vτ1(τ) > 0. The interpretation is that at a strong singularity, an extended body, e.g. a gravitational wave detector, is crushed to zero volume by the singularity. Tipler's definition does not take account of the possibility that (i) V → ∞ or (ii) V → finite, non-zero value, but with infinite stretching/crushing in orthogonal directions ('spaghettifying singularity'). Extended definition (Nolan 1999): strong if either V → 0,∞ or if for every τ1, there is an element ěc ξ of Jτ1 satisfying ||ěc ξ || -> 0. Otherwise weak. (Ori 2000): singularity is 'deformationally strong' if either (i) it is Tipler-strong or (ii) for every τ1, there is an element ěc ξ of Jτ1 satisfying ||ěc ξ || -> ∞ . Otherwise, deformationally weak...

  10. Results of nonendoscopic endonasal dacryocystorhinostomy

    Directory of Open Access Journals (Sweden)

    Preechawai P

    2012-08-01

    Full Text Available Passorn PreechawaiDepartment of Ophthalmology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandBackground: Surgical scarring on the face and disrupted anatomy in the medial canthal area following external dacryocystorhinostomy (DCR can be avoided by an endonasal approach. This study examined the outcome of direct visualization endonasal DCR, performed by young surgeons and residents.Methods: A retrospective case series of 75 consecutive endonasal DCRs performed under direct visualization from July 2002 to July 2004 were reviewed. Surgery was performed by surgeons and residents who had received no special training in the procedure. Full success was defined as no symptoms of tearing after surgery and anatomical patency with fluorescein flow on nasal endoscopy or patency to lacrimal syringing. Partial success was defined as a tearing decrease compared with prior to surgery and with anatomical patency, and failure was defined as no significant improvement in persistent tearing. The average follow-up duration was 26.83 ± 16.26 (range 6–55 months.Results: Seventy-five DCRs were performed on 63 patients (four male, 59 female of mean age 49.44 ± 16.63 (range 21–85 years. The surgery was successful in 54/75 eyes (72%, 37/54 eyes (68.5%, and 30/42 eyes (71.4% at 6, 12, and 24 months, respectively. Partial success was achieved in 13/75 (17.3%, 9/54 (16.7%, and 9/42 (21.4%, and the failure rates were 10.7%, 14.8%, and 7.1% at 6, 12, and 24 months, respectively. The overall functional success with this technique was 74.7% and the overall anatomical patency was 92.0%. There were no serious complications arising from the surgery; three minor complications were documented, ie, an incorrectly placed silicone tube in the lower canaliculus, tube prolapse, and postoperative bleeding which needed nasal packing and eventually a developed retention cyst in the nasal cavity.Conclusion: Endonasal DCR under direct visualization is a

  11. 1999 Annual report -- Generating results

    International Nuclear Information System (INIS)

    results and a consolidated financial statement, with the usual supporting information attached

  12. First half 2010 financial results

    International Nuclear Information System (INIS)

    The Supervisory Board of the AREVA group presents in this document the financial statements submitted by the Executive Board for the semester ended June 30, 2010. Areva backlog continued to rise in the first half of the year. Areva's revenue is up by more than 6% for the first six months to more than 4 billion euros. The performance of Areva's recurring business continues to improve, reflecting optimization plans deployed in all of the group's business units. However, Areva booked in the first half a non cash reversible accounting adjustment on the value of certain mining assets, following the publication in the second quarter of new prospective data on uranium prices, as well as an additional provision on the EPR project in Finland. Cumulated provisions on OL3 rose to 2.6 billion euros. Capitalizing on lessons learned from this project, Areva has reduced strongly the engineering hours needed for the completion of the nuclear steam supply system for the Taishan 1 and 2 EPR reactors. Net income attributable to owners of the parent rose to 843 million euros, including the 1.3 billion euro gain on the disposal of the Transmission and Distribution business, or 23.82 euros per share. For the full year of 2010, the group anticipates a substantial revenue and backlog growth, an increase in operating income excluding particular items, a negative operating income, and a strong increase in net income attributable to owners of the parent, which includes the capital gain on disposal of the Transmission and Distribution business. First half 2010 financial results in brief: - Backlog of euro 44.1 bn: +euro 1.2 bn compared with June 30, 2009; - Revenue of euro 4.158 bn: +6.4% compared with first half 2009; - Operating income excl. particular items: euro 213 m, for a 5.1% margin; - Operating income: -euro 485 m; - Net income group share: euro 843 m including the euro 1.27 bn gain on the sale of the T and D business; - Earnings per share: euro 23.82; - Net debt of euro 5.152 bn

  13. An overview of KSTAR results

    Science.gov (United States)

    Kwak, Jong-Gu; Oh, Y. K.; Yang, H. L.; Park, K. R.; Kim, Y. S.; Kim, W. C.; Kim, J. Y.; Lee, S. G.; Na, H. K.; Kwon, M.; Lee, G. S.; Ahn, H. S.; Ahn, J.-W.; Bae, Y. S.; Bak, J. G.; Bang, E. N.; Chang, C. S.; Chang, D. H.; Chen, Z. Y.; Cho, K. W.; Cho, M. H.; Choi, M.; Choe, W.; Choi, J. H.; Chu, Y.; Chung, K. S.; Diamond, P.; Delpech, L.; Do, H. J.; Eidietis, N.; England, A. C.; Ellis, R.; Evans, T.; Choe, G.; Grisham, L.; Gorelov, Y.; Hahn, H. S.; Hahn, S. H.; Han, W. S.; Hatae, T.; Hillis, D.; Hoang, T.; Hong, J. S.; Hong, S. H.; Hong, S. R.; Hosea, J.; Humphreys, D.; Hwang, Y. S.; Hyatt, A.; Ida, K.; In, Y. K.; Ide, S.; Jang, Y. B.; Jeon, Y. M.; Jeong, J. I.; Jeong, N. Y.; Jeong, S. H.; Jin, J. K.; Joung, M.; Ju, J.; Kawahata, K.; Kim, C. H.; Kim, Hee-Su; Kim, H. S.; Kim, H. J.; Kim, H. K.; Kim, H. T.; Kim, J. H.; Kim, J.; Kim, J. C.; Kim, Jong-Su; Kim, Jung-Su; Kim, J. H.; Kim, Kyung-Min; Kim, K. J.; Kim, K. P.; Kim, M. K.; Kim, S. T.; Kim, S. W.; Kim, Y. J.; Kim, Y. K.; Kim, Y. O.; Ko, J. S.; Ko, W. H.; Kogi, Y.; Kolemen, E.; Kong, J. D.; Kwak, S. W.; Kwon, J. M.; Kwon, O. J.; Lee, D. G.; Lee, D. R.; Lee, D. S.; Lee, H. J.; Lee, J.; Lee, J. H.; Lee, K. D.; Lee, K. S.; Lee, S. H.; Lee, S. I.; Lee, S. M.; Lee, T. G.; Lee, W.; Lee, W. L.; Lim, D. S.; Litaudon, X.; Lohr, J.; Mueller, D.; Moon, K. M.; Na, D. H.; Na, Y. S.; Nam, Y. U.; Namkung, W.; Narihara, K.; Oh, S. T.; Oh, D. G.; Ono, T.; Park, B. H.; Park, D. S.; Park, G. Y.; Park, H.; Park, H. T.; Park, J. K.; Park, J. S.; Park, M. K.; Park, S. H.; Park, S.; Park, Y. M.; Park, Y. S.; Parker, R.; Rhee, D. R.; Sabbagh, S. A.; Sakamoto, K.; Shiraiwa, S.; Seo, D. C.; Seo, S. H.; Seol, J. C.; Shi, Y. J.; Son, S. H.; Song, N. H.; Suzuki, T.; Terzolo, L.; Walker, M.; Wallace, G.; Watanabe, K.; Wang, S. J.; Woo, H. J.; Woo, I. S.; Yagi, M.; Yu, Y. W.; Yamada, I.; Yonekawa, Y.; Yoo, C. M.; You, K. I.; Yoo, J. W.; Yun, G. S.; Yu, M. G.; Yoon, S. W.; Xiao, W.; Zoletnik, S.; the KSTAR Team

    2013-10-01

    Since the first H-mode discharges in 2010, the duration of the H-mode state has been extended and a significantly wider operational window of plasma parameters has been attained. Using a second neutral beam (NB) source and improved tuning of equilibrium configuration with real-time plasma control, a stored energy of Wtot ˜ 450 kJ has been achieved with a corresponding energy confinement time of τE ˜ 163 ms. Recent discharges, produced in the fall of 2012, have reached plasma βN up to 2.9 and surpassed the n = 1 ideal no-wall stability limit computed for H-mode pressure profiles, which is one of the key threshold parameters defining advanced tokamak operation. Typical H-mode discharges were operated with a plasma current of 600 kA at a toroidal magnetic field BT = 2 T. L-H transitions were obtained with 0.8-3.0 MW of NB injection power in both single- and double-null configurations, with H-mode durations up to ˜15 s at 600 kA of plasma current. The measured power threshold as a function of line-averaged density showed a roll-over with a minimum value of ˜0.8 MW at \\bar{n}_e\\sim 2\\times 10^{19}\\,m^{-3} . Several edge-localized mode (ELM) control techniques during H-mode were examined with successful results including resonant magnetic perturbation, supersonic molecular beam injection (SMBI), vertical jogging and electron cyclotron current drive injection into the pedestal region. We observed various ELM responses, i.e. suppression or mitigation, depending on the relative phase of in-vessel control coil currents. In particular, with the 90° phase of the n = 1 RMP as the most resonant configuration, a complete suppression of type-I ELMs was demonstrated. In addition, fast vertical jogging of the plasma column was also observed to be effective in ELM pace-making. SMBI-mitigated ELMs, a state of mitigated ELMs, were sustained for a few tens of ELM periods. A simple cellular automata (‘sand-pile’) model predicted that shallow deposition near the pedestal

  14. An overview of KSTAR results

    International Nuclear Information System (INIS)

    Since the first H-mode discharges in 2010, the duration of the H-mode state has been extended and a significantly wider operational window of plasma parameters has been attained. Using a second neutral beam (NB) source and improved tuning of equilibrium configuration with real-time plasma control, a stored energy of Wtot ∼ 450 kJ has been achieved with a corresponding energy confinement time of τE ∼ 163 ms. Recent discharges, produced in the fall of 2012, have reached plasma βN up to 2.9 and surpassed the n = 1 ideal no-wall stability limit computed for H-mode pressure profiles, which is one of the key threshold parameters defining advanced tokamak operation. Typical H-mode discharges were operated with a plasma current of 600 kA at a toroidal magnetic field BT = 2 T. L–H transitions were obtained with 0.8–3.0 MW of NB injection power in both single- and double-null configurations, with H-mode durations up to ∼15 s at 600 kA of plasma current. The measured power threshold as a function of line-averaged density showed a roll-over with a minimum value of ∼0.8 MW at n-bar e∼2×1019 m-3. Several edge-localized mode (ELM) control techniques during H-mode were examined with successful results including resonant magnetic perturbation, supersonic molecular beam injection (SMBI), vertical jogging and electron cyclotron current drive injection into the pedestal region. We observed various ELM responses, i.e. suppression or mitigation, depending on the relative phase of in-vessel control coil currents. In particular, with the 90° phase of the n = 1 RMP as the most resonant configuration, a complete suppression of type-I ELMs was demonstrated. In addition, fast vertical jogging of the plasma column was also observed to be effective in ELM pace-making. SMBI-mitigated ELMs, a state of mitigated ELMs, were sustained for a few tens of ELM periods. A simple cellular automata (‘sand-pile’) model predicted that shallow deposition near the pedestal foot induced

  15. Atrazine Triggers DNA Damage Response and Induces DNA Double-Strand Breaks in MCF-10A Cells

    Directory of Open Access Journals (Sweden)

    Peixin Huang

    2015-06-01

    Full Text Available Atrazine, a pre-emergent herbicide in the chloro-s-triazine family, has been widely used in crop lands and often detected in agriculture watersheds, which is considered as a potential threat to human health. Although atrazine and its metabolites showed an elevated incidence of mammary tumors in female Sprague–Dawley (SD rats, no molecular evidence was found relevant to its carcinogenesis in humans. This study aims to determine whether atrazine could induce the expression of DNA damage response-related proteins in normal human breast epithelial cells (MCF-10A and to examine the cytotoxicity of atrazine at a molecular level. Our results indicate that a short-term exposure of MCF-10A to an environmentally-detectable concentration of atrazine (0.1 µg/mL significantly increased the expression of tumor necrosis factor receptor-1 (TNFR1 and phosphorylated Rad17 in the cells. Atrazine treatment increased H2AX phosphorylation (γH2AX and the formation of γH2AX foci in the nuclei of MCF-10A cells. Atrazine also sequentially elevated DNA damage checkpoint proteins of ATM- and RAD3-related (ATR, ATRIP and phospho-Chk1, suggesting that atrazine could induce DNA double-strand breaks and trigger the DNA damage response ATR-Chk1 pathway in MCF-10A cells. Further investigations are needed to determine whether atrazine-triggered DNA double-strand breaks and DNA damage response ATR-Chk1 pathway occur in vivo.

  16. Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype

    International Nuclear Information System (INIS)

    The cellular and molecular mechanisms that underlie skeletal abnormalities in defective Recql4-related syndromes are poorly understood. Our objective in this study was to explore the function of Recql4 in osteoblast biology both in vitro and in vivo. Immunohistochemistry on adult mouse bone showed Recql4 protein localization in active osteoblasts around growth plate, but not in fully differentiated osteocytes. Consistent with this finding, Recql4 gene expression was high in proliferating mouse osteoblastic MC3T3.E1 cells and decreased as cells progressively lost their proliferation activity during differentiation. Recql4 overexpression in osteoblastic cells exhibited higher proliferation activity, while its depletion impeded cell growth. In addition, bone marrow stromal cells from male Recql4+/- mice had fewer progenitor cells, including osteoprogenitors, indicated by reduced total fibroblast colony forming units (CFU-f) and alkaline phosphatase-positive CFU-f colonies concomitant with reduced bone mass. These findings provide evidence that Recql4 functions as a regulatory protein during osteoprogenitor proliferation, a critical cellular event during skeleton development

  17. Mutations in SYNGAP1 Cause Intellectual Disability, Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency

    DEFF Research Database (Denmark)

    Berryer, Martin H; Hamdan, Fadi F; Klitten, Laura L;

    2013-01-01

    De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP-activating protein, cause nonsyndromic intellectual disability (NSID). All disease-causing point mutations identified until now in SYNGAP1 are truncating, raising the possibility of an association between this type of mutations and NSID...

  18. Haploinsufficiency of novel FOXG1B variants in a patient with severe mental retardation, brain malformations and microcephaly

    DEFF Research Database (Denmark)

    Shoichet, Sarah A; Kunde, Stella-Amrei; Viertel, Petra;

    2005-01-01

    We have investigated the chromosome abnormalities in a female patient exhibiting a severe cognitive disability associated with complete agenesis of the corpus callosum and microcephaly. The patient carries a balanced de novo translocation t(2;14)(p22;q12), together with a neighbouring 720 kb inve...

  19. Heterozygous Lmna(delK32) mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity

    DEFF Research Database (Denmark)

    Cattin, M. E.; Bertrand, A. T.; Schlossarek, S.;

    2013-01-01

    . The pathomechanisms linking mutations to DCM remain to be elucidated. We investigated the phenotype and associated pathomechanisms of heterozygous Lmna(K32/) (Het) knock-in mice, which carry a human mutation. Het mice developed a cardiac-specific phenotype. Two phases, with two different pathomechanisms, could...... itself has a clear deleterious effect on engineered heart tissues force of contraction, it also leads to the nuclear aggregation of viral-mediated expression of K32-lamin. In conclusion, Het mice are the first knock-in Lmna model with cardiac-specific phenotype at the heterozygous state. Altogether, our...

  20. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease

    NARCIS (Netherlands)

    Zhou, Qing; Wang, Hongying; Schwartz, Daniella M; Stoffels, Monique; Park, Yong Hwan; Zhang, Yuan; Yang, Dan; Demirkaya, Erkan; Takeuchi, Masaki; Tsai, Wanxia Li; Lyons, Jonathan J; Yu, Xiaomin; Ouyang, Claudia; Chen, Celeste; Chin, David T; Zaal, Kristien; Chandrasekharappa, Settara C; P Hanson, Eric; Yu, Zhen; Mullikin, James C; Hasni, Sarfaraz A; Wertz, Ingrid E; Ombrello, Amanda K; Stone, Deborah L; Hoffmann, Patrycja; Jones, Anne; Barham, Beverly K; Leavis, Helen L; van Royen, Annet; Sibley, Cailin; Batu, Ezgi D; Gül, Ahmet; Siegel, Richard M; Boehm, Manfred; Milner, Joshua D; Ozen, Seza; Gadina, Massimo; Chae, JaeJin; Laxer, Ronald M; Kastner, Daniel L; Aksentijevich, Ivona

    2015-01-01

    Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflamma

  1. Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis

    DEFF Research Database (Denmark)

    Rasmussen, Torsten B; Nissen, Peter H; Palmfeldt, Johan;

    2014-01-01

    unrelated patients with AC identified 10 different PKP2 mutations in 12 index patients. One patient, heterozygous for a PKP2 nonsense mutation, developed severe heart failure and underwent cardiac transplantation. Western blotting and immunohistochemistry of the explanted heart showed a significant decrease......BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The disease is most often caused by mutations in the desmosomal gene for plakophilin-2 (PKP2), which is expressed in both myocardial and...

  2. Experimental results on radiative kaon decays

    International Nuclear Information System (INIS)

    This paper reviews the current status of experimental results on radiative kaon decays. Several experiments at BNL, CERN and FNAL have recently or will soon complete data collection; as a result, there are several new results

  3. Ranking XPaths for extracting search result records

    NARCIS (Netherlands)

    Trieschnigg, Dolf; Tjin-Kam-Jet, Kien; Hiemstra, Djoerd

    2012-01-01

    Extracting search result records (SRRs) from webpages is useful for building an aggregated search engine which combines search results from a variety of search engines. Most automatic approaches to search result extraction are not portable: the complete process has to be rerun on a new search result

  4. 16 CFR 1610.8 - Reporting results.

    Science.gov (United States)

    2010-01-01

    ... FLAMMABILITY OF CLOTHING TEXTILES The Standard § 1610.8 Reporting results. (a) The reported result shall be the classification before or after refurbishing, whichever is the more severe; and based on this result, the textile... results for each specimen that is burned. (1) For Plain Surface Textile Fabrics: DNIDid not...

  5. Accuracy of results with NASTRAN modal synthesis

    Science.gov (United States)

    Herting, D. N.

    1978-01-01

    A new method for component mode synthesis was developed for installation in NASTRAN level 17.5. Results obtained from the new method are presented, and these results are compared with existing modal synthesis methods.

  6. Presidential General Election Results - 2012 - Direct Download

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map layer portrays Presidential general election results for 2012, with results reported by county or county equivalent, for the 50 United States and the...

  7. NEW RESULTS ON ESTIMATES FOR SINGULAR VALUES

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    New results are provided to estimate matrix singular values in terms of partial absolute deleted row sums and column sums. Illustrative examples are presented to show comparisons with results in literature.

  8. Results of Evolution Supervised by Genetic Algorithms

    CERN Document Server

    Jäntschi, Lorentz; Bălan, Mugur C; Sestraş, Radu E

    2010-01-01

    A series of results of evolution supervised by genetic algorithms with interest to agricultural and horticultural fields are reviewed. New obtained original results from the use of genetic algorithms on structure-activity relationships are reported.

  9. Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/m cell cycle arrest and apoptosis.

    Directory of Open Access Journals (Sweden)

    Hefen Sun

    Full Text Available The treatment of human hepatocellular carcinoma (HCC cell lines with (+-isocorydine, which was isolated and purified from Papaveraceae sp. plants, resulted in a growth inhibitory effect caused by the induction of G2/M phase cell cycle arrest and apoptosis. We report that isocorydine induces G2/M phase arrest by increasing cyclin B1 and p-CDK1 expression levels, which was caused by decreasing the expression and inhibiting the activation of Cdc25C. The phosphorylation levels of Chk1 and Chk2 were increased after ICD treatment. Furthermore, G2/M arrest induced by ICD can be disrupted by Chk1 siRNA but not by Chk2 siRNA. In addition, isocorydine treatment led to a decrease in the percentage of CD133(+ PLC/PRF/5 cells. Interestingly, isocorydine treatment dramatically decreased the tumorigenicity of SMMC-7721 and Huh7 cells. These findings indicate that isocorydine might be a potential therapeutic drug for the chemotherapeutic treatment of HCC.

  10. Replication factor C3 of Schizosaccharomyces pombe, a small subunit of replication factor C complex, plays a role in both replication and damage checkpoints.

    Science.gov (United States)

    Shimada, M; Okuzaki, D; Tanaka, S; Tougan, T; Tamai, K K; Shimoda, C; Nojima, H

    1999-12-01

    We report here the isolation and functional analysis of the rfc3(+) gene of Schizosaccharomyces pombe, which encodes the third subunit of replication factor C (RFC3). Because the rfc3(+) gene was essential for growth, we isolated temperature-sensitive mutants. One of the mutants, rfc3-1, showed aberrant mitosis with fragmented or unevenly separated chromosomes at the restrictive temperature. In this mutant protein, arginine 216 was replaced by tryptophan. Pulsed-field gel electrophoresis suggested that rfc3-1 cells had defects in DNA replication. rfc3-1 cells were sensitive to hydroxyurea, methanesulfonate (MMS), and gamma and UV irradiation even at the permissive temperature, and the viabilities after these treatments were decreased. Using cells synchronized in early G2 by centrifugal elutriation, we found that the replication checkpoint triggered by hydroxyurea and the DNA damage checkpoint caused by MMS and gamma irradiation were impaired in rfc3-1 cells. Association of Rfc3 and Rad17 in vivo and a significant reduction of the phosphorylated form of Chk1 in rfc3-1 cells after treatments with MMS and gamma or UV irradiation suggested that the checkpoint signal emitted by Rfc3 is linked to the downstream checkpoint machinery via Rad17 and Chk1. From these results, we conclude that rfc3(+) is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor. PMID:10588638

  11. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Institute of Scientific and Technical Information of China (English)

    Hai Jiang; Jianchun Wu; Chen He; Wending Yang; Honglin Li

    2009-01-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdkl activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chkl and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  12. v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage.

    Science.gov (United States)

    Ikeuchi, Masayoshi; Fukumoto, Yasunori; Honda, Takuya; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

    2016-06-02

    An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of γH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor. v-Src induces the phosphorylation of KAP1 at Ser824, Chk2 at Thr68, and Chk1 at Ser345, suggesting the activation of the ATM/ATR pathway. Caffeine decreases the number of cells having chromosome bridges at a concentration incapable of inhibiting Chk1 phosphorylation at Ser345. These results suggest that v-Src induces chromosome bridges via generation of DNA damage and the subsequent DNA damage response, possibly by homologous recombination. A chromosome bridge gives rise to the accumulation of DNA damage directly through chromosome breakage and indirectly through cytokinesis failure-induced multinucleation. We propose that v-Src-induced chromosome bridge formation is one of the causes of the v-Src-induced malignant progression of cancer cells.

  13. IceCube Results and PINGU Perspectives

    DEFF Research Database (Denmark)

    Koskinen, David Jason

    2015-01-01

    The last three years of IceCube operation with the completed detector have resulted in a plethora of results, including the first observation of high energy astrophysical neutrinos, tests of a possible neutrino flux from atmospheric charm meson decay, and competitive results of neutrino oscillation...

  14. Setting Priorities Personal Values, Organizational Results

    CERN Document Server

    (CCL), Center for Creative Leadership

    2011-01-01

    To be a successful leader, you need to get results. To get results, you need to set priorities. This book can help you do a better job of setting priorities, recognizing the personal values that motivate your decision making, the probable trade-offs and consequences of your decisions, and the importance of aligning your priorities with your organization's expectations. In this way you can successfully meet organizational objectives and consistently produce results.

  15. Towards structured representation of academic search results

    OpenAIRE

    Mirylenka, Daniil

    2015-01-01

    Searching for scientific publications is a tedious task, especially when exploring an unfamiliar domain. Typical scholarly search engines produce lengthy unstructured result lists, which are difficult to comprehend, interpret and browse.An informative visual summary could convey useful information about the returned results as a whole, without the need to sift through individual publications.The first contribution of this thesis is a novel method of representing academic search results wit...

  16. Recent Results from the ZEUS Experiment

    CERN Document Server

    Smith, W H; Abramowicz, H; Adamczyk, L; Adamus, M; Adler, V; Aghuzumtsyan, G; Antonioli, P; Antonov, A; Arneodo, M; Bailey, D S; Bamberger, A; Barakbaev, A N; Barbagli, G; Barbi, M; Bari, G; Barreiro, F; Bartsch, D; Basile, M; Bauerdick, L A T; Behrens, U; Bell, M; Bellagamba, L; Benen, A; Bertolin, A; Bhadra, S; Bloch, I; Bodmann, B; Bold, T; Boos, E G; Borras, K; Boscherini, D; Brock, I; Brook, N H; Brugnera, R; Brümmer, N; Bruni, A; Bruni, G; Bussey, P J; Butterworth, J M; Bylsma, B; Caldwell, A; Capua, M; Cara Romeo, G; Carli, T; Carlin, R; Catterall, C D; Chekanov, S; Chiochia, V; Chwastowski, J; Ciborowski, J; Ciesielski, R; Cifarelli, Luisa; Cindolo, F; Cloth, P; Cole, J E; Collins-Tooth, C; Contin, A; Cooper-Sarkar, A M; Coppola, N; Cormack, C; Corradi, M; Corriveau, F; Cottrell, A; D'Agostini, Giulio; Dal Corso, F; Danilov, P; Dannheim, D; De Pasquale, S; Dementiev, R K; Derrick, M; Deshpande, Abhay A; Devenish, R C E; Dhawan, S; Dolgoshein, B A; Doyle, A T; Drews, G; Durkin, L S; Dusini, S; Eisenberg, Y; Ermolov, P F; Eskreys, Andrzej; Ferrando, J; Ferrero, M I; Figiel, J; Filges, D; Foster, B; Foudas, C; Fourletov, S; Fourletova, J; Fricke, U; Fusayasu, T; Gabareen, A; Gallo, E; Garfagnini, A; Geiser, A; Genta, C; Gialas, I; Giusti, P; Gladilin, L K; Gladkov, D; Glasman, C; Gliga, S; Goers, S; Golubkov, Yu A; Goncalo, R; González, O; Göttlicher, P; Grabowska-Bold, I; Grijpink, S; Grzelak, G; Gutsche, O; Gwenlan, C; Haas, T; Hain, W; Hall-Wilton, R; Hamatsu, R; Hamilton, J; Hanlon, S; Hart, J C; Hartmann, H; Hartner, G; Hartner, G F; Heaphy, E A; Heath, G P; Heath, H F; Helbich, M; Heusch, C A; Hilger, E; Hillert, S; Hirose, T; Hochman, D; Holm, U; Iacobucci, G; Iga, Y; Inuzuka, M; Irrgang, P; Jakob, H P; Jones, T W; Kagawa, S; Kahle, B; Kaji, H; Kananov, S; Kappes, A; Kataoka, Y; Yamazaki, M; Katkov, I I; Katz, U F; Kcira, D; Khein, L A; Kim, J Y; Kim, Y K; Kind, O; Kisielewska, D; Kitamura, S; Klimek, K; Koffeman, E; Kohno, T; Kooijman, P; Koop, T; Korzhav, I A; Kotanski, A; Kötz, U; Kowal, A M; Kowal, M; Kowalski, H; Kowalski, T; Krakauer, D; Kramberger, G; Kreisel, A; Krumnack, N; Kuze, M; Kuzmin, V A; Labarga, L; Labes, H; Lainesse, J; Lammers, S; Lee, J H; Lee, S W; Lelas, D; Levchenko, B B; Levman, G M; Levy, A; Li, L; Lightwood, M S; Lim, H; Lim, I T; Limentani, S; Ling, T Y; Liu, X; Löhr, B; Lohrmann, E; Loizides, J H; Long, K R; Longhin, A; Lukina, O Yu; Lupi, A; Luzniak, P; Maddox, E; Magill, S; Mankel, R; Margotti, A; Marini, G; Martin, J F; Mastroberardino, A; Matsuzawa, K; Mattingly, M C K; McCubbin, N A; Mellado, B; Melzer-Pellmann, I A; Menary, S R; Metlica, F; Meyer, U; Milite, M; Mirea, A; Monaco, V; Montanari, A; Moritz, M; Musgrave, B; Nagano, K; Nania, R; Nguyen, C N; Nigro, A; Ning, Y; Nishimura, T; Notz, D; Nowak, R J; Oh, B Y; Olkiewicz, K; Pac, M Y; Padhi, S; Paganis, S; Palmonari, F; Parenti, A; Park, I H; Patel, S; Paul, E; Pavel, N; Pawlak, J M; Pelfer, P G; Pellegrino, A; Pesci, A; Petrucci, M C; Piotrzkowski, K; Plucinsky, P P; Pokrovskiy, N S; Polini, A; Posocco, M; Proskuryakov, A S; Przybycien, M B; Rautenberg, J; Raval, A; Reeder, D D; Ren, Z; Renner, R; Repond, J; Riveline, U; Karshon, M; Robins, S; Rodrigues, E; Rosin, M; Rurua, L; Ruspa, M; Sacchi, R; Salehi, H; Sartorelli, G; Savin, A A; Saxon, D H; Schagen, S; Schioppa, M; Schlenstedt, S; Schmidke, W B; Schneekloth, U; Sciulli, F; Scott, J; Selonke, F; Shcheglova, L M; Skillicorn, I O; Slominski, W; Soares, M; Solano, A; Son, D; Sosnovtsev, V V; Stairs, D G; Stanco, L; Standage, J; Stifutkin, A; Stoesslein, U; Stonjek, S; Stopa, P; Straub, P B; Suchkov, S; Susinno, G; Suszycki, L; Sutton, M R; Sztuk, J; Szuba, D; Szuba, J; Tandler, J; Tapper, A D; Tapper, R J; Tassi, E; Tawara, T; Terron, J; Tiecke, H G; Tokushuku, K; Tsurugai, T; Turcato, M; Tymieniecka, T; Ukleja, A; Ukleja, J; Vázquez, M; Velthuis, J J; Vlasov, N N; Voss, K C; Walczak, R; Walsh, R; Wang, M; Weber, A; Wessoleck, H; West, B J; Whitmore, J J; Wick, K; Wiggers, L; Wills, H H; Wing, M; Wolf, G; Yamada, S; Yamashita, T; Yoshida, R; Youngman, C; Zawiejski, L; Zeuner, W; Zhautykov, B O; Zichichi, A; Ziegler, A; Zotkin, S A; De Wolf, E; Del Peso, J

    2004-01-01

    A summary of recent results from ZEUS is presented. New ZEUS results from HERA-1 data include Structure Functions, QCD fits, analysis of hadronic final states, precision measurements of alpha_s, production of heavy flavor mesons and baryons and studies of diffraction. Results from the new HERA-II running include the measurement of the cross section for polarized charged current events and charm events tagged with the new ZEUS vertex detector.

  17. Monthly results of measurements, August 1986

    International Nuclear Information System (INIS)

    This report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface water, underground water, sewage water, drinking water, food chain (milk, vegetables, fishes) seawater around nuclear plant sites and other sites. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident

  18. Monthly results of measurements, October 1986

    International Nuclear Information System (INIS)

    This October 1986 report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface water, underground water, sewage water, drinking water, food chain (milk, vegetables, fishes), sea water around nuclear plant sites and other sites. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident, with an exceptional control of migratory birds

  19. Monthly results of measurements, May 1987

    International Nuclear Information System (INIS)

    This report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface waters, underground water, drinking water, sewage water, food chain (milk, vegetables, fishes), sea water around nuclear plant sites and other sites, sediments. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident

  20. Monthly results of measurements, November 1989

    International Nuclear Information System (INIS)

    This report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface water, underground water, sewage water, drinking water, food chain (milk, vegetables, fishes), sea water around nuclear plant sites and other sites. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident

  1. Monthly results of measurements, Nov 1988

    International Nuclear Information System (INIS)

    This report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface water, underground water, sewage water, drinking water, food chain (milk, vegetables, fishes), sea water around nuclear plant sites and other sites. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident

  2. Monthly results of measurements, May 1986

    International Nuclear Information System (INIS)

    This May 1986 report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface water, underground water, sewage water, drinking water, food chain (milk, vegetables, fishes), sea water around nuclear plant sites and other sites. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident. More than 5000 samples are analyzed

  3. Monthly results of measurements, April 1989

    International Nuclear Information System (INIS)

    This report of the SCPRI exposes an interpretation of the principal results concerning the routine monitoring of environmental radioactivity in France: atmospheric dusts, rainwater, surface water, underground water, sewage water, drinking water, food chain (milk, vegetables, fishes), sea water around nuclear plant sites and other sites. The activities of various radioisotopes are presented in tables. This report exposes also the results of special radiation measurements resulting from the Chernobyl accident

  4. BABAR non-CP physics results

    International Nuclear Information System (INIS)

    The BABAR experiment at SLAC has just presented its first physics results, with the primary attention on the expected measurement of the CP-violating sin(2β) parameter. Apart from the observation of CP asymmetries, the first year of operation has led to a variety of results that are already competitive with the world's best measurements. We present a selection of these results including BB-bar mixing, B lifetimes and a variety of branching fractions, in particular for rare B decays

  5. Annual results 2004; Resultats annuels 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This 2004 annual evaluation of the french RTE company (electric power transport network) provides information on the 2004 results on: institutional information, financial results, customers and market, industrial resources, environment and consultation, human resources and international aspects. (A.L.B.)

  6. CMS supersymmetry and exotic Higgs results

    Science.gov (United States)

    Yohay, R.; CMS Collaboration

    2016-07-01

    A selection of results covering searches for supersymmetric particles and exotic decays of the Higgs boson are presented. These results are based on 8 TeV proton-proton collision data collected by the Compact Muon Solenoid experiment at the Large Hadron Collider.

  7. Pluto results on jets and QCD

    International Nuclear Information System (INIS)

    Results obtained with the PLUTO detector at PETRA are presented. Multihadron final states have been analysed with respect to clustering, energy-energy correlations and transverse momenta in jets. QCD predictions for hard gluon emission and soft gluon-quark cascades are discussed. Results on α/sub s/ and the gluon spin are given

  8. Review of Recent Results in Charm Physics

    CERN Document Server

    Engelfried, J

    2003-01-01

    A biased review of recent results in charm physics is presented. New results on D0 anti-D0 mixing, rare decays of D0 and D+/-, scalar resonances in D+ and Ds decays, and new decay modes and mass measurements in Lambda_c, Xi_c, Omega_c, and Xi_cc are discussed.

  9. Recent Electroweak Results from the LHC

    CERN Document Server

    Helary, Louis; The ATLAS collaboration

    2016-01-01

    Slides for conference Aspen 2016. The talk is about recent Electroweak results at the LHC. It is focused on multi-boson physics and boson EWK production. It is supposed to summarize results from ATLAS, CMS and LHCb, but given the topic it contains only material from ATLAS and CMS.

  10. Two convergence results for continuous descent methods

    Directory of Open Access Journals (Sweden)

    Simeon Reich

    2003-03-01

    Full Text Available We consider continuous descent methods for the minimization of convex functionals defined on general Banach space. We establish two convergence results for methods which are generated by regular vector fields. Since the complement of the set of regular vector fields is $sigma$-porous, we conclude that our results apply to most vector fields in the sense of Baire's categories.

  11. Students' Homework and TIMSS 2003 Mathematics Results

    Science.gov (United States)

    Mikk, Jaan

    2006-01-01

    An aspect of the complex relationship between students homework and academic achievement (Cooper, Robinson, and Patall, 2006) was examined by correlating TIMSS 2003 mathematics results with the data about homework in 46 countries of the TIMSS study. The TIMSS results had no statistically significant correlation with the teachers' emphasis on…

  12. Tablet PCs, Academic Results and Educational Inequalities

    Science.gov (United States)

    Ferrer, Ferran; Belvis, Esther; Pamies, Jordi

    2011-01-01

    This article is the result of a study carried out in 2008 and 2009 by a team from the Autonomous University of Barcelona in order to evaluate the implementation of the Digital Whiteboard Program in public schools in the region of Aragon (Spain). The following pages present some of the results obtained during the study. More specifically, this…

  13. Absolute-stability results in infinite dimensions

    NARCIS (Netherlands)

    Curtain, RF; Logemann, H; Staffans, O

    2004-01-01

    We derive absolute-stability results of Popov and circle-criterion type for infinite-dimensional systems in an input-output setting. Our results apply to feedback systems in which the linear part is the series interconnection of an input-output stable linear system and an integrator, and the nonline

  14. ANISOTROPIC BIQUADRATIC ELEMENT WITH SUPERCLOSE RESULT

    Institute of Scientific and Technical Information of China (English)

    Dongyang SHI; Shipeng MAO; Hui LIANG

    2006-01-01

    The main aim of this paper is to study the convergence of biquadratic finite element for the second order problem on anisotropic meshes. By using some novel approaches and techniques, the optimal error estimates are obtained. At the same time, the anisotropic superclose results are also achieved. Furthermore, the numerical results are given to demonstrate our theoretical analysis.

  15. Comparison of instability theory with simulation results

    International Nuclear Information System (INIS)

    The results of a quantitative comparison between linear instability theory and simulation results for a third order charge fluctuation mode in a quadrupole - focused beam are summarized. The theory is found to provide a good account of the initial instability exhibited by the simulation computations

  16. Recent adiabaticity results from orbit calculations

    International Nuclear Information System (INIS)

    There has been much activity recently in an attempt to find a straightforward method of predicting the limits of adiabatic behavior in high-beta magnetic-mirror configurations. The particle-orbit code TIBRO was used to obtain numerical results on nonadiabatic behavior with which the predictions of theoretical expressions can be compared. These results are summarized. (MOW)

  17. Uniform dimension results for Gaussian random fields

    Institute of Scientific and Technical Information of China (English)

    WU DongSheng; XIAO YiMin

    2009-01-01

    Let X = {X(t), t ∈ RN} be a Gaussian random field with values in Rd defined by x(t) = (x1(t),…,xd(t)), At∈RN.(1)The properties of space and time anisotropy of X and their connections to uniform Hausdorff dimension results are discussed. It is shown that in general the uniform Hausdorff dimension result does not hold for the image sets of a space-anisotropic Gaussian random field X. When X is an (N, d)-Gaussian random field as in (1), where X1,..., Xd are independent copies of a real valued, centered Gaussian random field Xo which is anisotropic in the time variable. We establish uniform Hausdorff dimension results for the image sets of X. These results extend the corresponding results on one-dimensional Brownian motion, fractional Brownian motion and the Brownian sheet.

  18. Format SPARQL Query Results into HTML Report

    Directory of Open Access Journals (Sweden)

    Dr Sunitha Abburu

    2013-07-01

    Full Text Available SPARQL is one of the powerful query language for querying semantic data. It is recognized by the W3C as a query language for RDF. As an efficient query language for RDF, it has defined several query result formats such as CSV, TSV and XML etc. These formats are not attractive, understandable and readable. The results need to be converted in an appropriate format so that user can easily understand. The above formats require additional transformations or tool support to represent the query result in user readable format. The main aim of this paper is to propose a method to build HTML report dynamically for SPARQL query results. This enables SPARQL query result display, in HTML report format easily, in an attractive understandable format without the support of any additional or external tools or transformation.

  19. Explicit Optimal Hardness via Gaussian stability results

    CERN Document Server

    De, Anindya

    2012-01-01

    The results of Raghavendra (2008) show that assuming Khot's Unique Games Conjecture (2002), for every constraint satisfaction problem there exists a generic semi-definite program that achieves the optimal approximation factor. This result is existential as it does not provide an explicit optimal rounding procedure nor does it allow to calculate exactly the Unique Games hardness of the problem. Obtaining an explicit optimal approximation scheme and the corresponding approximation factor is a difficult challenge for each specific approximation problem. An approach for determining the exact approximation factor and the corresponding optimal rounding was established in the analysis of MAX-CUT (KKMO 2004) and the use of the Invariance Principle (MOO 2005). However, this approach crucially relies on results explicitly proving optimal partitions in Gaussian space. Until recently, Borell's result (Borell 1985) was the only non-trivial Gaussian partition result known. In this paper we derive the first explicit optimal...

  20. Query Expansion Based on Clustered Results

    CERN Document Server

    Liu, Ziyang; Chen, Yi

    2011-01-01

    Query expansion is a functionality of search engines that suggests a set of related queries for a user-issued keyword query. Typical corpus-driven keyword query expansion approaches return popular words in the results as expanded queries. Using these approaches, the expanded queries may correspond to a subset of possible query semantics, and thus miss relevant results. To handle ambiguous queries and exploratory queries, whose result relevance is difficult to judge, we propose a new framework for keyword query expansion: we start with clustering the results according to user specified granularity, and then generate expanded queries, such that one expanded query is generated for each cluster whose result set should ideally be the corresponding cluster. We formalize this problem and show its APX-hardness. Then we propose two efficient algorithms named iterative single-keyword refinement and partial elimination based convergence, respectively, which effectively generate a set of expanded queries from clustered r...

  1. Results Processing in Heterogeneous Digital Libraries

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In the heterogeneous digital libraries, users are allowed to have access to data of different modalities, from different information sources, and ranked by different criteria. This paper,which assumes that each information retrieval model is satisfactory in its own context, proposes two results processing methods: Ranking by Sources (RBS) and Simply Merging Results (SMR). It defines satisfied ranking, which satisfies most source rankings, and satisfied distance to indicate how a specific source ranking suits the satisfied ranking. RBS ranks sources by their satisfied distances and groups the results by sources. SMR, using source scoring function distributions, substitutes normalized scores for original scores from sources, and then merges the results using these normalized scores. The results show they are very feasible and efficient in the heterogeneous environment

  2. Uniform dimension results for Gaussian random fields

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Let X = {X(t),t ∈ RN} be a Gaussian random field with values in Rd defined by X(t) =(X1(t),...,Xd(t)), t ∈ RN.(1) The properties of space and time anisotropy of X and their connections to uniform Hausdorff dimension results are discussed.It is shown that in general the uniform Hausdorff dimension result does not hold for the image sets of a space-anisotropic Gaussian random field X.When X is an(N,d)-Gaussian random field as in(1),where X1,...,Xd are independent copies of a real valued,centered Gaussian random field X0 which is anisotropic in the time variable.We establish uniform Hausdorff dimension results for the image sets of X.These results extend the corresponding results on one-dimensional Brownian motion,fractional Brownian motion and the Brownian sheet.

  3. Operative results of closed tibial plateau fractures

    Directory of Open Access Journals (Sweden)

    Mathur Hitin

    2005-01-01

    Full Text Available Background: Management of tibial plateau fractures remains challenging because of their number, variety and associated soft tissue injuries that further augment their complexity. Comparison of operative results in recent reports has been difficult due to a lack of standard fracture classification scheme and uniform standardized objective criteria for evaluating results. Methods: Between August 1998 to December 2002, 27 closed tibial plateau fractures were treated operatively using methods and principles advocated by AO/ASIF and followed up for an average of 35.74 months (range 24-68 months. Fractures were classified according to Schatzker′s staging system and results evaluated using Rasmussen′s 30-point clinical grading system and Rasmussen′s radiological evaluation of the knee at a minimum follow up of 2 years. Results: Type II was the most common fracture type (9 cases followed by type I (6 cases. There were 37% excellent and 51.85% good functional results with only 3 patients having unacceptable results. The mean Rasmussen′s functional score was 25.062 (range 15-30. Minimal fixation in comminuted or depressed fractures as compared to rigid fixation was the cause of unacceptable results. Loss of knee range of motion in a few cases was attributed to delayed knee mobilization in these cases. Using Rasmussen′s radiological grading, 2 patients had excellent results and 81.48 % patients had good results. Only 3 patients had poor radiological results. The mean Rasmussen′s radiological score was 15.33 (range 10-18. Moreover, clinical evaluation did not correlate with the follow up radiograph. Conclusion: Anatomic reduction and rigid internal fixation followed by early knee motion and partial weight bearing during bone healing are the cornerstones in the treatment of tibial plateau fractures. Standard fracture classification, uniform reporting and evaluating criteria, along with detailed analysis of uniform treatment methods, has helped us

  4. Experimental rotordynamic coefficient results for honeycomb seals

    Science.gov (United States)

    Elrod, David A.; Childs, Dara W.

    1988-01-01

    Test results (leakage and rotordynamic coefficients) are presented for seven honeycomb-stator smooth-rotor seals. Tests were carried out with air at rotor speeds up to 16,000 cpm and supply pressures up to 8.2 bars. Test results for the seven seals are compared, and the most stable configuration is identified based on the whirl frequency ratio. Results from tests of a smooth-rotor/smooth-stator seal, a teeth-on-stator labyrinth seal, and the most stable honeycomb seal are compared.

  5. Semantic Clustering of Search Engine Results.

    Science.gov (United States)

    Soliman, Sara Saad; El-Sayed, Maged F; Hassan, Yasser F

    2015-01-01

    This paper presents a novel approach for search engine results clustering that relies on the semantics of the retrieved documents rather than the terms in those documents. The proposed approach takes into consideration both lexical and semantics similarities among documents and applies activation spreading technique in order to generate semantically meaningful clusters. This approach allows documents that are semantically similar to be clustered together rather than clustering documents based on similar terms. A prototype is implemented and several experiments are conducted to test the prospered solution. The result of the experiment confirmed that the proposed solution achieves remarkable results in terms of precision.

  6. First scientific results from the Estonian Grid

    CERN Document Server

    Hektor, A; Kadastik, M; Skaburskas, K; Teder, H; Hektor, Andi; Anton, Lauri; Kadastik, Mario; Skaburskas, Konstantin; Teder, Hardi

    2004-01-01

    We present first scientific results, technical details and recent developments in the Estonian Grid. Ideas and concepts behind Grid technology are described. We mention some most crucial parts of a Grid system, as well as some unique possibilities in the Estonian situation. Scientific applications currently running on Estonian Grid are listed. We discuss the first scientific computations and results the Estonian Grid. The computations show that the middleware is well chosen and the Estonian Grid has remarkable stability and scalability. The authors present the collected results and experiences of the development of the Estonian Grid and add some ideas of the near future of the Estonian Grid.

  7. Semantic Clustering of Search Engine Results

    Directory of Open Access Journals (Sweden)

    Sara Saad Soliman

    2015-01-01

    Full Text Available This paper presents a novel approach for search engine results clustering that relies on the semantics of the retrieved documents rather than the terms in those documents. The proposed approach takes into consideration both lexical and semantics similarities among documents and applies activation spreading technique in order to generate semantically meaningful clusters. This approach allows documents that are semantically similar to be clustered together rather than clustering documents based on similar terms. A prototype is implemented and several experiments are conducted to test the prospered solution. The result of the experiment confirmed that the proposed solution achieves remarkable results in terms of precision.

  8. Unfavourable results with distraction in craniofacial skeleton

    Directory of Open Access Journals (Sweden)

    Rajiv Agarwal

    2013-01-01

    Full Text Available Distraction osteogenesis has revolutionised the management of craniofacial abnormalities. The technique however requires precise planning, patient selection, execution and follow-up to achieve consistent and positive results and to avoid unfavourable results. The unfavourable results with craniofacial distraction stem from many factors ranging from improper patient selection, planning and use of inappropriate distraction device and vector. The present study analyses the current standards and techniques of distraction and details in depth the various errors and complications that may occur due to this technique. The commonly observed complications of distraction have been detailed along with measures and suggestions to avoid them in clinical practice.

  9. Review of Physics Results from the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Bandurin, D. [Virginia U.; Bernardi, G. [Paris U., VI-VII; Gerber, C. [Chicago U., EFI; Junk, T. [Fermilab; Juste, A. [Barcelona, IFAE; Kotwal, A. [Duke U.; Lewis, J. [Fermilab; Mesropian, C. [Rockefeller U.; Schellman, H. [Northwestern U.; Sekaric, J. [Kansas U.; Toback, D. [Texas A-M; Van Kooten, R. [Indiana U.; Vellidis, C. [Fermilab; Zivkovic, L. [Clemson U.

    2015-02-27

    We present a comprehensive review of the physics results obtained by the CDF and D0 collaborations up to summer 2014, with emphasis on those achieved in the Run II of the Tevatron collider which delivered a total integrated luminosity of ~10 fb$^{-1}$ at $\\sqrt{s} = 1.96~{\\rm TeV}$. The results are presented in six main physics topics: QCD, Heavy Flavor, Electroweak, Top quark, Higgs boson and searches for New Particles and Interactions. The characteristics of the accelerator, detectors, and the techniques used to achieve these results are also briefly summarized.

  10. Analytic results for the Tsallis thermodynamic variables

    CERN Document Server

    Bhattacharyya, Trambak; Mogliacci, Sylvain

    2016-01-01

    We analytically investigate the thermodynamic variables of a hot and dense system, in the framework of the Tsallis non-extensive classical statistics. After a brief review, we start by recalling the corresponding massless limits for all the thermodynamic variables. We then present the detail of calculation for the exact massive result regarding the pressure -- valid for all values of the $q$-parameter -- as well as the Tsallis $T$-, $\\mu$- and $m$- parameters, the former characterizing the non-extensivity of the system. The results for other thermodynamic variables, in the massive case, readily follow from appropriate differentiations of the pressure, for which we provide the necessary formulas. For the convenience of the reader, we tabulate all of our results. A special emphasis is put on the method used in order to perform these computations, which happens to reduce cumbersome momentum integrals into simpler ones. Numerical consistency between our analytic results and the corresponding usual numerical integ...

  11. [Benton Lake nest survey results 1993

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This dataset is nest survey results from Benton Lake National Wildlife Refuge from highland habitats and island habitats, and also includes a chart of duck nest...

  12. Focus on Communication: NIH Research to Results

    Science.gov (United States)

    ... Current Issue Past Issues Special Section: Focus on Communication NIH Research to Results Past Issues / Fall 2008 ... grew new hair cells. Read More "Focus on Communication" Articles Living with Hearing Loss / Anatomy of the ...

  13. The journal of irreproducible results II

    CERN Document Server

    Scherr, George H

    1997-01-01

    Compilation of offbeat science papers from the Journal of Irreproducible Results, including: Emotion in the Rat Face; Foamy Beer; Cooking with Potential Energy; The Large-Cake Cutting Problem; Siamese Twinning in Gummy Bears; much more.

  14. Existence results for integral viscoelastic fluids

    CERN Document Server

    Chupin, Laurent

    2011-01-01

    We consider the flows of viscoelastic fluid which obey a constitutive law of integral type. The existence and uniqueness results for solutions of the initial boundary value problem are proved, and the stationary case is studied.

  15. Innovation Impact: Breakthrough Research Results (Brochure)

    Energy Technology Data Exchange (ETDEWEB)

    2013-07-01

    The Innovation Impact brochure captures key breakthrough results across NREL's primary areas of renewable energy and energy efficiency research: solar, wind, bioenergy, transportation, buildings, analysis, and manufacturing technologies.

  16. CRUMP 2003 Selected Water Sample Results

    Data.gov (United States)

    U.S. Environmental Protection Agency — Point locations and water sampling results performed in 2003 by the Church Rock Uranium Monitoring Project (CRUMP) a consortium of organizations (Navajo Nation...

  17. New Quality Metrics for Web Search Results

    Science.gov (United States)

    Metaxas, Panagiotis Takis; Ivanova, Lilia; Mustafaraj, Eni

    Web search results enjoy an increasing importance in our daily lives. But what can be said about their quality, especially when querying a controversial issue? The traditional information retrieval metrics of precision and recall do not provide much insight in the case of web information retrieval. In this paper we examine new ways of evaluating quality in search results: coverage and independence. We give examples on how these new metrics can be calculated and what their values reveal regarding the two major search engines, Google and Yahoo. We have found evidence of low coverage for commercial and medical controversial queries, and high coverage for a political query that is highly contested. Given the fact that search engines are unwilling to tune their search results manually, except in a few cases that have become the source of bad publicity, low coverage and independence reveal the efforts of dedicated groups to manipulate the search results.

  18. Some Results on the Simultaneous Approximation

    Institute of Scientific and Technical Information of China (English)

    M. R. Haddadi∗

    2014-01-01

    In this paper, we give some result on the simultaneous proximinal subset and simultaneous Chebyshev in the uniformly convex Banach space. Also we give relation between fixed point theory and simultaneous proximity.

  19. Search Result Diversification Based on Query Facets

    Institute of Scientific and Technical Information of China (English)

    胡莎; 窦志成; 王晓捷; 继荣

    2015-01-01

    In search engines, different users may search for different information by issuing the same query. To satisfy more users with limited search results, search result diversification re-ranks the results to cover as many user intents as possible. Most existing intent-aware diversification algorithms recognize user intents as subtopics, each of which is usually a word, a phrase, or a piece of description. In this paper, we leverage query facets to understand user intents in diversification, where each facet contains a group of words or phrases that explain an underlying intent of a query. We generate subtopics based on query facets and propose faceted diversification approaches. Experimental results on the public TREC 2009 dataset show that our faceted approaches outperform state-of-the-art diversification models.

  20. Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1.

    Directory of Open Access Journals (Sweden)

    Carla Manuela Abreu

    2013-04-01

    Full Text Available The mediators of the DNA damage response (DDR are highly phosphorylated by kinases that control cell proliferation, but little is known about the role of this regulation. Here we show that cell cycle phosphorylation of the prototypical DDR mediator Saccharomyces cerevisiae Rad9 depends on cyclin-dependent kinase (CDK complexes. We find that a specific G2/M form of Cdc28 can phosphorylate in vitro the N-terminal region of Rad9 on nine consensus CDK phosphorylation sites. We show that the integrity of CDK consensus sites and the activity of Cdc28 are required for both the activation of the Chk1 checkpoint kinase and its interaction with Rad9. We have identified T125 and T143 as important residues in Rad9 for this Rad9/Chk1 interaction. Phosphorylation of T143 is the most important feature promoting Rad9/Chk1 interaction, while the much more abundant phosphorylation of the neighbouring T125 residue impedes the Rad9/Chk1 interaction. We suggest a novel model for Chk1 activation where Cdc28 regulates the constitutive interaction of Rad9 and Chk1. The Rad9/Chk1 complex is then recruited at sites of DNA damage where activation of Chk1 requires additional DDR-specific protein kinases.

  1. Grp/DChk1 is required for G(2)-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable

    NARCIS (Netherlands)

    de Vries, HI; Uyetake, L; Lemstra, W; Brunsting, JF; Su, TT; Kampinga, HH; Sibon, OCM

    2005-01-01

    Cell-cycle checkpoints are signal-transduction pathways required to maintain genomic stability in dividing cells. Previously, it was reported that two kinases essential for checkpoint signalling, Chk1 and Chk2 are structurally conserved. In contrast to yeast, Xenopus and mammals, the Chk1- and Chk2-

  2. Rare earth optogalvanic spectroscopy: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Destro, Marcelo G.; Neri, Jose W.; Rodrigues, Nicolau A.S.; Silveira, Carlos A.B.; Riva, Rudimar [Instituto de Estudos Avancados (IEAv/EFO), Sao Jose dos Campos, SP (Brazil). Div. de Fotonica]. E-mail: destro@ieav.cta.br; Victor, Alessandro R. [Instituto Tecnologico de Aeronautica (ITA), Sao Jose dos Campos, SP (Brazil)

    2008-07-01

    The IEAv has special interest in the studies of rare earth isotope applications in laser medium and integrated optics as well as aerospace research. We are starting to work with Ytterbium, Erbium, Dysprosium and Neodymium laser selective photoionization research. This paper describes the preliminary results of emission and optogalvanic spectroscopy obtained from a Neodymium hollow cathode lamps. Furthermore these results were used to setup our laser systems to work to leads a Nd isotopes selective laser photoionization. (author)

  3. Some results on stability of difference systems

    Directory of Open Access Journals (Sweden)

    Xiao-Song Yang

    2002-01-01

    Full Text Available This paper presents some new results on existence and stability of equilibrium or periodic points for difference systems. First sufficient conditions of existence of asymptotically stable equilibrium point as well as the asymptotic stability of given equilibrium point are given for second order or delay difference systems. Then some similar results on existence of asymptotically stable periodic (equilibrium points to general difference systems are presented.

  4. Results for the French national FADN

    OpenAIRE

    Desbois, Dominique; Butault, Jean-Pierre; Delame, Nathalie; Zardet, Guillaume

    2011-01-01

    This report presents the results of implementing and testing the GECOM on the basis of the French national FADN. Depending on the extent of analysis which additionally has been carried out for this country on the basis of the EU FADN, this country chapter provides a full overview of results and validation, while presenting the differences between cost estimates based on national vs. EU FADN.

  5. Results of integral experiments on VERA assemblies

    International Nuclear Information System (INIS)

    The VERA reactor at AWRE has been used to study problems in the UK fast power reactor programme and in research reactor design. However, its main function has been to provide experimental results for small fast assemblies against which calculations can be compared to improve the nuclear cross-sections used. This report outlines the experimental methods used in the VERA work and gives the results. (author)

  6. Quantum chromodynamics results from HERA and JLAB

    Indian Academy of Sciences (India)

    Katja Krüger

    2012-10-01

    Recent QCD results from electron–proton interactions at HERA and JLAB are presented. Inclusive cross-section measurements as well as studies of the hadronic final state like jet production or the production of heavy quarks are discussed. The results are compared with perturbative QCD predictions and their impact on the determination of the parton density functions of the proton as well as of the strong coupling α s is discussed.

  7. Bent functions results and applications to cryptography

    CERN Document Server

    Tokareva, Natalia

    2015-01-01

    Bent Functions: Results and Applications to Cryptography offers a unique survey of the objects of discrete mathematics known as Boolean bent functions. As these maximal, nonlinear Boolean functions and their generalizations have many theoretical and practical applications in combinatorics, coding theory, and cryptography, the text provides a detailed survey of their main results, presenting a systematic overview of their generalizations and applications, and considering open problems in classification and systematization of bent functions. The text is appropriate for novices and advanced

  8. Rare earth optogalvanic spectroscopy: preliminary results

    International Nuclear Information System (INIS)

    The IEAv has special interest in the studies of rare earth isotope applications in laser medium and integrated optics as well as aerospace research. We are starting to work with Ytterbium, Erbium, Dysprosium and Neodymium laser selective photoionization research. This paper describes the preliminary results of emission and optogalvanic spectroscopy obtained from a Neodymium hollow cathode lamps. Furthermore these results were used to setup our laser systems to work to leads a Nd isotopes selective laser photoionization. (author)

  9. Results of the /sup 37/Cl experiment

    Energy Technology Data Exchange (ETDEWEB)

    Davis, R Jr

    Present results of the /sup 37/Cl experiment to measure the flux of /sup 8/B neutrinos from the sun are presented. The results are plotted, and the technical details are discussed. From a /sup 37/Ar production rate above the background of 0.30, the possible solar neutrino rate was deduced to be 5.31 x (0.30 +- 0.08) = 1.6 +- 0.4 SNU. (JFP)

  10. Results from STAR experiment at RHIC

    Indian Academy of Sciences (India)

    Bedangadas Mohanty; STAR Collaboration

    2006-11-01

    We present some of the important experimental results from nucleus–nucleus collision studies carried out by the STAR experiment at Relativistic Heavy Ion Collider (RHIC). The results suggests that central Au+Au collisions at RHIC has produced a dense and rapidly thermalizing matter with initial energy densities above the critical values predicted by lattice QCD for establishment of a quark-gluon plasma (QGP).

  11. Recent BES results on charmonium decays

    CERN Document Server

    Yuan, Chang-Zheng

    2007-01-01

    In this talk, we present the recent results on charmonium decays from the BES experiment at the BEPC collider. The analyses are based on a 14 million psi(2S) events data sample. We report results on leptonic decays, hadronic decays, and radiative decays of psi(2S), as well as hadronic decays of chi_cJ states and rare or forbidden decays of J/psi.

  12. New results from AMS cosmic ray measurements

    OpenAIRE

    Huang, M. A.

    2002-01-01

    The Alpha Magnetic Spectrometer (AMS) is a detector designed to search for antimatter in the cosmic rays. The physics results from the test flight in June 1998 are analyzed and published. This paper reviews the results in the five published papers of the AMS collaboration, updates the current understanding of two puzzles, albedo $e^+/e^-$ and albedo $^3$He, and disscusses the influence of albedo particles.

  13. Web Search Results Summarization Using Similarity Assessment

    Directory of Open Access Journals (Sweden)

    Sawant V.V.

    2014-06-01

    Full Text Available Now day’s internet has become part of our life, the WWW is most important service of internet because it allows presenting information such as document, imaging etc. The WWW grows rapidly and caters to a diversified levels and categories of users. For user specified results web search results are extracted. Millions of information pouring online, users has no time to surf the contents completely .Moreover the information available is repeated or duplicated in nature. This issue has created the necessity to restructure the search results that could yield results summarized. The proposed approach comprises of different feature extraction of web pages. Web page visual similarity assessment has been employed to address the problems in different fields including phishing, web archiving, web search engine etc. In this approach, initially by enters user query the number of search results get stored. The Earth Mover's Distance is used to assessment of web page visual similarity, in this technique take the web page as a low resolution image, create signature of that web page image with color and co-ordinate features .Calculate the distance between web pages by applying EMD method. Compute the Layout Similarity value by using tag comparison algorithm and template comparison algorithm. Textual similarity is computed by using cosine similarity, and hyperlink analysis is performed to compute outward links. The final similarity value is calculated by fusion of layout, text, hyperlink and EMD value. Once the similarity matrix is found clustering is employed with the help of connected component. Finally group of similar web pages i.e. summarized results get displayed to user. Experiment conducted to demonstrate the effectiveness of four methods to generate summarized result on different web pages and user queries also.

  14. Cosmetic results of breast conserving therapy

    International Nuclear Information System (INIS)

    Mean follow-up time of 192 women (pT1: 71.9%, pT2: 28.1%) was 4.5 years (median: 4.0 years). 26.6% of them were nodal positive. Positive nodal status correlated with high tumor grading (p=0.0001). Ten patients developed distant metastases; one of them subsequent to having suffered a loco-regional failure. Eight loco-regional failures occurred, 3 of them before radiotherapy (salvage). Following radiotherapy altogether 5 loco-regional failures (=2.6%) were found; 3 women concerning were pre-, 2 postmenopausal. Three of these patients died, in 1 case occurred distant metastasis. Seventeen patients died, 3 of them presenting loco-regional failure, 8 of them showing distant metastasis. Sixty-four women were examined for cosmesis with the following result: a poor result was observed twice, a fair result 13 times, a good result 34 and an excellent result 15 times. Self-assessment was significantly better than observer's assessment. Third-degree late sequelae were found once, second-degree was seen 11 times, first-degree 38 times and no visible late sequelae were observed 14 times. The use of wedges was followed with borderline significance (p=0.06) either by a better cosmesis and fewer late sequelae. Neither the type of surgery nor the width of the fields nor the quality of radiation (Co60 or 6 MVX) nor boost-application influenced the cosmetic result. Measured circumferences and distances showed no significant differences in the groups of the patients with poor or fair and good or excellent cosmesis. The temperature of the seized and contralateral breast showed no significant difference as well. With increasing distance from primary therapy the cosmetic results deteriorated. (orig./MG)

  15. Predictive aging results in radiation environments

    Science.gov (United States)

    Gillen, Kenneth T.; Clough, Roger L.

    1993-06-01

    We have previously derived a time-temperature-dose rate superposition methodology, which, when applicable, can be used to predict polymer degradation versus dose rate, temperature and exposure time. This methodology results in predictive capabilities at the low dose rates and long time periods appropriate, for instance, to ambient nuclear power plant environments. The methodology was successfully applied to several polymeric cable materials and then verified for two of the materials by comparisons of the model predictions with 12 year, low-dose-rate aging data on these materials from a nuclear environment. In this paper, we provide a more detailed discussion of the methodology and apply it to data obtained on a number of additional nuclear power plant cable insulation (a hypalon, a silicone rubber and two ethylene-tetrafluoroethylenes) and jacket (a hypalon) materials. We then show that the predicted, low-dose-rate results for our materials are in excellent agreement with long-term (7-9 year) low-dose-rate results recently obtained for the same material types actually aged under bnuclear power plant conditions. Based on a combination of the modelling and long-term results, we find indications of reasonably similar degradation responses among several different commercial formulations for each of the following "generic" materials: hypalon, ethylene-tetrafluoroethylene, silicone rubber and PVC. If such "generic" behavior can be further substantiated through modelling and long-term results on additional formulations, predictions of cable life for other commercial materials of the same generic types would be greatly facilitated.

  16. Nebraska wind resource assessment first year results

    Energy Technology Data Exchange (ETDEWEB)

    Hurley, P.J.F.; Vilhauer, R. [RLA Consulting, Inc., Bothell, WA (United States); Stooksbury, D. [Univ. of Nebraska, Lincoln, NE (United States)

    1996-12-31

    This paper presents the preliminary results from a wind resource assessment program in Nebraska sponsored by the Nebraska Power Association. During the first year the measured annual wind speed at 40 meters ranged from 6.5 - 7.5 m/s (14.6 - 16.8 mph) at eight stations across the state. The site selection process is discussed as well as an overview of the site characteristics at the monitoring locations. Results from the first year monitoring period including data recovery rate, directionality, average wind speeds, wind shear, and turbulence intensity are presented. Results from the eight sites are qualitatively compared with other midwest and west coast locations. 5 figs., 2 tabs.

  17. Preliminary results in surgery of Parkinson's disease.

    Science.gov (United States)

    Nasser, J A; Confort, C I; Ferraz, A; Bouza, A A

    1998-09-01

    The authors present the preliminary results of 20 patients selected to be operated on between January 1996 and April 1997. These patients presented one of the present indications for stereotactic posteroventral pallidotomy (PVP), such as: rigidity, akinesia/bradykinesia, gait dysfunction, drug induced dyskinesias and tremor. Every patient of this protocol was evaluated by: UPDRS score, Schwab and England scale, Hoehn and Yahr Staging Scale before and after surgery. The results in 3 months showed a remarkable improvement after PVP (P < 0.01) in all functional assessments, except for facial expression, speech and posture. The morbidity was 5%. 5 patients (25%) who were in Hoehn and Yahr 5 underwent a bilateral simultaneous PVP. In 5 patients (25%), who had tremor, during the PVP, VIM thalamotomy was added. These preliminary results, suggest that PVP is highly effective for PD symptoms. PMID:9850746

  18. Results of radiation protection programmes on mammography

    International Nuclear Information System (INIS)

    In this paper, we present the results of mammography quality control tests related to the work with Portuguese mammography equipment, either in conventional or in digital mammography computed radiography, showing the main differences in the tested equipments. Quality control in mammography is a very special area of quality control in radiology, which demands relatively high knowledge on physics. Digital imaging is changing the standards of the radiographic imaging. Regarding mammography, this is yet a controversial issue owing to some limitations of the digital detectors, like the resolution for instance. A complete set of results regarding radiation protection of the patients submitted to mammography diagnosis is presented. A discussion of the quality image parameters and its interpretation in conventional and digital mammography is presented. In conclusion, we present a sample of results that can be considered as characteristics of mammography equipment in Portugal. (authors)

  19. Cytology result entry without using the keyboard.

    Science.gov (United States)

    Aller, R D; DeWitt, C

    1994-01-01

    Many keystrokes are needed to enter routine gynecologic cytology results into many computer systems. Not only is this quite time consuming, but typing errors cannot be avoided and are not always detected before the report is sent to the clinician. Because of continuing shortages of staff time and the desire to avoid transcription errors, we began using $400 bar code wands to enter cytology results and billing information. No changes in our laboratory information system software or tables were necessary. Accession number labels are preprinted on a stand-alone printer. Bar code sheets, containing common keystroke sequences, are printed using a standard Macintosh computer and Laserwriter printer. Scanning the bar codes exactly emulates those keystrokes typed on the keyboard. We have entered the results of > 99% of our gynecologic cytology cases in the past two years without touching the keyboard. PMID:8091908

  20. Preliminary results in surgery of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    NASSER JOSÉ AUGUSTO

    1998-01-01

    Full Text Available The authors present the preliminary results of 20 patients selected to be operated on between January 1996 and April 1997. These patients presented one of the present indications for stereotactic postero-ventral pallidotomy (PVP, such as: rigidity, akinesia/bradykinesia, gait dysfunction, drug induced dyskinesias and tremor. Every patient of this protocol was evaluated by: UPDRS score, Schwab and England scale, Hoehn and Yahr Staging Scale before and after surgery. The results in 3 months showed a remarkable improvement after PVP (P<0.01 in all functional assessments, except for facial expression, speech and posture. The morbidity was 5%. 5 patients (25% who were in Hoehn and Yahr 5 underwent a bilateral simultaneous PVP. In 5 patients (25%, who had tremor, during the PVP, VIM thalamotomy was added. These preliminary results suggest that PVP is highly effective for PD symptoms

  1. Heavy Ion results from RHIC-BNL

    Directory of Open Access Journals (Sweden)

    Esumi Shinlchi

    2013-05-01

    Full Text Available Recent results from heavy ion collision experiments from RHIC at BNL are presented and discussed in terms of Quark Gluon Plasm properties, such as partonic collectivity and partonic energy loss. The experimental results with direct photons and heavy quarks have given important additional insights of the plasma on top of what has been known with light hadrons. Higher order event anisotropies and the related results have provided the geometrical, temporal and dynamical information of the plasma. The beam energy dependence of the various measurements could reveal the structure of QCD phase diagram and possibly the critical point in the diagram, where the properties of phase transition are expected to change drastically.

  2. Recent results from NA61/SHINE

    CERN Document Server

    Puławski, Szymon

    2015-01-01

    The main physics goals of the NA61/SHINE programme on strong interactions are the study of the properties of the onset of deconfinement and the search for signatures of the critical point of strongly interacting matter. These goals are pursued by performing an energy (beam momentum 13A -158A GeV/c) and system size (p+p, p+Pb, Be+Be, Ar+Sc, Xe+La) scan. This publication reviews results and plans of NA61/SHINE. In particular, recent inclusive spectra and new results on fluctuations and correlations of identified hadrons in inelastic p+p and centrality selected Be+Be interactions at the SPS energies are presented. The energy dependence of quantities inspired by the Statistical Model of the Early Stage (kink, horn and step) show unexpected behavior in p+p collisions. The NA61/SHINE results are compared with the corresponding data of other experiments and model predictions.

  3. Interpreting Results from the Multinomial Logit Model

    DEFF Research Database (Denmark)

    Wulff, Jesper

    2015-01-01

    This article provides guidelines and illustrates practical steps necessary for an analysis of results from the multinomial logit model (MLM). The MLM is a popular model in the strategy literature because it allows researchers to examine strategic choices with multiple outcomes. However, there see...... suitable for both interpretation and communication of results. The pratical steps are illustrated through an application of the MLM to the choice of foreign market entry mode.......This article provides guidelines and illustrates practical steps necessary for an analysis of results from the multinomial logit model (MLM). The MLM is a popular model in the strategy literature because it allows researchers to examine strategic choices with multiple outcomes. However, there seem...

  4. Evaluation of the PISC trials results

    International Nuclear Information System (INIS)

    This report gives the results of the analysis carried out in the manner described in PISC report no.4, to compare the defects indicated by ultrasonic examination with those discovered by a destructive examination. The analysis was repeated three times; once for ultrasonic examination using the PISC procedure but with as much as possible subjective interpretation from the teams removed, once for ultrasonic examination using the PISC procedure incorporating the subjective interpretation of the teams, and once for ultrasonic examination using a variety of alternative techniques. Results are given in the form of tables and figures for each reference defect (i.e. those found by the destructive examination) in turn. Correlations, when they exist, are presented between the parameters describing the performance of the ultrasonic examination procedures and the parameters describing the reference defects. From the global set of results conclusions are drawn concerning the efficiency of the ultrasonic procedures for detecting, sizing, locating and correct rejection of defects

  5. European intercomparison of diagnostic dosemeters: results

    International Nuclear Information System (INIS)

    The measurement protocol for the 1990 CEC sponsored intercomparison is described and the results have been analysed. The majority of participants achieved good results, within 10% deviation of the correct value. Differences in performance can be linked to how each national centre organised the intercomparison and to national arrangements for similar measurements, particularly legislative requirements. Furthermore, certain types of instruments tended to perform well, particularly those with a flat energy response for the X ray qualities used. Participants who used instruments dedicated to mammographic and diagnostic X ray qualities, tended to obtain the best results. The greatest scope for improvement in the accuracy of measurements is in mammography, and this is related to the use of dedicated mammographic chambers. (14 figs)

  6. Stability results for random discrete structures

    CERN Document Server

    Samotij, Wojciech

    2011-01-01

    Two years ago, Conlon and Gowers, and Schacht proved general theorems that allow one to transfer a large class of extremal combinatorial results from the deterministic to the probabilistic setting. Even though the two papers solve the same set of long-standing open problems in probabilistic combinatorics, the methods used in them vary significantly and therefore yield results that are not comparable in certain aspects. The theorem of Schacht can be applied in a more general setting and yields stronger probability estimates, whereas the one of Conlon and Gowers also implies random versions of some structural statements such as the famous stability theorem of Erdos and Simonovits. In this paper, we bridge the gap between these two transference theorems. Building on the approach of Schacht, we prove a general theorem that allows one to transfer deterministic stability results to the probabilistic setting that is somewhat more general and stronger then the one obtained by Conlon and Gowers. We then use this theor...

  7. Livermore Big Trees Park: 1998 Results

    Energy Technology Data Exchange (ETDEWEB)

    Mac Queen, D; Gallegos, G; Surano, K

    2002-04-18

    This report is an in-depth study of results from environmental sampling conducted in 1998 by the Lawrence Livermore National Laboratory (LLNL) at Big Trees Park in the city of Livermore. The purpose of the sampling was to determine the extent and origin of plutonium found in soil at concentrations above fallout-background levels in the park. This report describes the sampling that was conducted, the chemical and radio-chemical analyses of the samples, the quality control assessments and statistical analyses of the analytical results, and LLNL's interpretations of the results. It includes a number of data analyses not presented in LLNL's previous reports on Big Trees Park.

  8. Results of Stapes Surgery in Our Clinic

    Directory of Open Access Journals (Sweden)

    Reşit Murat Açıkalın

    2015-12-01

    Full Text Available Aim: The aim of this study was to analyze the results of stapes surgery, which is done to improve the air-bone gap in otosclerosis, and to show its benefit in hearing. Methods: We retrospectively analyzed 42 patients in terms of audiologic evaluation results, smoking status, tinnitus and complications. Air-bone gap closure was classified as successful (gap 10 dB and unsuccessful (no gap closure or worse. Results: The mean preoperative air-bone gap was 37.43 dB. Air-bone gap closure was successful or partially successful in 39 patients (92.86% and unsuccessful in two patients (4.76. There was no relationship between the success of the surgery and smoking. All 42 had tinnitus preoperatively. Tinnitus healed in 28 patients postoperatively. One patient had tympanic membrane perforation postoperatively. Conclusion: Although there are some complications, stapes surgery in patients with otosclerosis is a reliable and effective option.

  9. Efficient Diversification of Web Search Results

    CERN Document Server

    Capannini, Gabriele; Perego, Raffaele; Silvestri, Fabrizio

    2011-01-01

    In this paper we analyze the efficiency of various search results diversification methods. While efficacy of diversification approaches has been deeply investigated in the past, response time and scalability issues have been rarely addressed. A unified framework for studying performance and feasibility of result diversification solutions is thus proposed. First we define a new methodology for detecting when, and how, query results need to be diversified. To this purpose, we rely on the concept of "query refinement" to estimate the probability of a query to be ambiguous. Then, relying on this novel ambiguity detection method, we deploy and compare on a standard test set, three different diversification methods: IASelect, xQuAD, and OptSelect. While the first two are recent state-of-the-art proposals, the latter is an original algorithm introduced in this paper. We evaluate both the efficiency and the effectiveness of our approach against its competitors by using the standard TREC Web diversification track test...

  10. Overview of the recent CMS Results

    CERN Document Server

    Lanyov, Alexander V

    2013-01-01

    We discuss the results of searches for Higgs boson and various new physics phenomena in pp collisions at 7 and 8 TeV delivered by LHC and collected with the CMS detector in 2011–2012. A new boson with a mass near 125 GeV has been observed above the expected background with the most significant excess of events in the two decay modes $\\gamma \\gamma$ and ZZ$^*$. The results of combination of five channels are presented. Limits for new physics phenomena with various experimental signatures (dileptons, diphotons, dijets, multijets, etc.), have been determined. The results of studies of electroweak, top quark and QCD processes and heavy-ion physics are also presented.

  11. Preliminary results in surgery of Parkinson's disease.

    Science.gov (United States)

    Nasser, J A; Confort, C I; Ferraz, A; Bouza, A A

    1998-09-01

    The authors present the preliminary results of 20 patients selected to be operated on between January 1996 and April 1997. These patients presented one of the present indications for stereotactic posteroventral pallidotomy (PVP), such as: rigidity, akinesia/bradykinesia, gait dysfunction, drug induced dyskinesias and tremor. Every patient of this protocol was evaluated by: UPDRS score, Schwab and England scale, Hoehn and Yahr Staging Scale before and after surgery. The results in 3 months showed a remarkable improvement after PVP (P < 0.01) in all functional assessments, except for facial expression, speech and posture. The morbidity was 5%. 5 patients (25%) who were in Hoehn and Yahr 5 underwent a bilateral simultaneous PVP. In 5 patients (25%), who had tremor, during the PVP, VIM thalamotomy was added. These preliminary results, suggest that PVP is highly effective for PD symptoms.

  12. An overview of recent ATLAS results

    CERN Document Server

    Nikolic-Audit, Irena; The ATLAS collaboration

    2013-01-01

    The ATLAS experiment at the LHC collider has been successfully taking data since the end of 2009, both in proton-proton collisions at center of mass energies of 7 and 8 TeV, and in heavy ion collisions. The ATLAS detector has been designed to cover a wide range of physics topics, from the search for the Higgs boson, precision measurements of Standard Model physics, heavy flavor physics, and to maximize the potential for the discovery of new physics. In this presentation, some of the most important recent ATLAS results will be given for the Standard Model measurements, for the searches for supersymmetry and exotica, and for the heavy ion results. All of the results concerning the properties of the newly discovered Higgs boson are presented in a separate contribution by IlyaTsukerman \\cite{higgs} in these proceedings.

  13. Some Results on Halo Research at RIBLL

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Last years,several experiments about halo nuclei were performed at RIBLL.On the analyzing and fitting the data by using Glauber theory with some assumptions,following some results were deduced.1.~8B shows a proton halo structure.The reaction cross section σR of 54 MeV/u~8B on Si was measured as 1634±49 mb.The density distribution of ~8B was studied through a fitting procedure on the enhancement of the σR at low energies including the high energy data by using Glauber theory.The result shows a long tail ...

  14. SPARQL Query Result Explanation for Linked Data

    OpenAIRE

    Hasan, Rakebul; Endris, Kemele M.; Gandon, Fabien

    2014-01-01

    In this paper, we present an approach to explain SPARQL query results for Linked Data using why-provenance. We present a non-annotation-based algorithm to generate why-provenance and show its feasibility for Linked Data. We present an explanation-aware federated query processor prototype and show the presentation of our explanations. We present a user study to evaluate the impacts of our explanations. Our study shows that our query result explanations are helpful for end users to understand t...

  15. Resummed Results for Hadron Collider Observables

    Directory of Open Access Journals (Sweden)

    McAslan Heather

    2016-01-01

    Full Text Available Event shapes are invaluable QCD tools for theoretical calculations and experimental measurements. We revise the definition of these observables in e+e− annihilation and in hadron collisions, and give a review of the state-of-the-art results for their resummation. Then we detail how recent work on the re-summation of event shapes in electron-positron annihilation can provide us with the tools to extend resummation of generic hadronic event shapes to NNLL accuracy. We match our findings to fixed-order results at NNLO accuracy, showing the sizeable effects of resummation in the relevant regions of phase space.

  16. [Preliminary results of treatment with aflibercept].

    Science.gov (United States)

    Blăjan, Codruta; Nicula, D; Rusu, Ioana

    2014-01-01

    The paper presents the first results concerning the Aflibercept (Eylea) treatment, the last antiVEGF approved for treatment of the age related macular degeneration (AMD), neovascular form and for macular edema due to the central retinal vein occlusion. The treatment was applied to patients presenting AMD, ME and other diseases: myopic and idiopatic choroidal neovascularisation, central serous choroidopathy (CSC) or diabetic macular edema (DME). The results were good: improvement of the visual acuity, resolution of the intraretinal fluids and macular edema. Although we did not notice major side-effects, resistance or tachyphylaxis, we noticed some recurrences.

  17. Chemistry of the Galactic Bulge: New Results

    Science.gov (United States)

    Zoccali, Manuela; Hill, Vanessa; Barbuy, Beatriz; Lecureur, Aurelie; Minniti, Dante; Renzini, Alvio; Gonzalez, Oscar; Gómez, Ana; Ortolani, Sergio

    2009-06-01

    VLT-FLAMES observations provide by far the largest sample of high dispersion spectra of Bulge red giants available. Five years of work on these 900 spectra have yielded the abundances of different elements in the Milky Way Bulge, and new results on its formation. The results so far include the Bulge metallicity distribution, the Bulge metallicity gradient, the metallicity dependence on kinematics, the history of enrichment with alpha-elements, as well as the lithium abundance. The evidence collected on Milky Way Bulge chemical enrichment supports a rapid early formation scenario, and the metallicity gradient argues against formation via secular bar evolution.

  18. Establishing precision and accuracy in PDV results

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, Matthew E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Howard, Marylesa [National Security Technologies, LLC. (NSTec), North Las Vegas, NV (United States); Diaz, Abel [National Security Technologies, LLC. (NSTec), Los Alamos, NM (United States)

    2016-04-19

    We need to know uncertainties and systematic errors because we create and compare against archival weapons data, we constrain the models, and we provide scientific results. Good estimates of precision from the data record are available and should be incorporated into existing results; reanalysis of valuable data is suggested. Estimates of systematic errors are largely absent. The original work by Jensen et al. using gun shots for window corrections, and the integrated velocity comparison with X-rays by Schultz are two examples where any systematic errors appear to be <1% level.

  19. Predictions of High Energy Experimental Results

    Directory of Open Access Journals (Sweden)

    Comay E.

    2010-10-01

    Full Text Available Eight predictions of high energy experimental results are presented. The predictions contain the $Sigma ^+$ charge radius and results of two kinds of experiments using energetic pionic beams. In addition, predictions of the failure to find the following objects are presented: glueballs, pentaquarks, Strange Quark Matter, magnetic monopoles searched by their direct interaction with charges and the Higgs boson. The first seven predictions rely on the Regular Charge-Monopole Theory and the last one relies on mathematical inconsistencies of the Higgs Lagrangian density.

  20. First results of the CAKE experiment

    CERN Document Server

    Chiarusi, T; Cecchini, S; Di Ferdinando, D; Giacomelli, G; Kumar, A; Patrizii, L; Togo, V; Valieri, C

    2003-01-01

    We present the preliminary results of the cosmic abundances below the knee energies (CAKE) experiment for the study of the primary cosmic- ray composition and for the search of exotic particles in the primary cosmic radiation. CAKE uses CR39** registered trademark and Lexan nuclear track detectors, which were calibrated with beams of 158 A Ge V Pb ions and 1 A GeV Fe ions at the CERN and BNL accelerators, respectively. Results based on the analysis of a first data sample are shown.