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Sample records for pink1 mutation share

  1. Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype

    DEFF Research Database (Denmark)

    van Nuenen, BF; Siebner, Hartwig; Weiss, MM

    2008-01-01

    inherited Parkinson disease alters the cortical control of sequential finger movements. METHODS: Nonmanifesting individuals carrying a single heterozygous Parkin (n = 13) or PINK1 (n = 9) mutation and 23 healthy controls without these mutations were studied with functional MRI (fMRI). During f......MRI, participants performed simple sequences of three thumb-to-finger opposition movements with their right dominant hand. Since heterozygous Parkin and PINK1 mutations cause a latent dopaminergic nigrostriatal dysfunction, we predicted a compensatory recruitment of those rostral premotor areas that are normally...... rostral dorsal premotor cortex in mutation carriers but not in controls. Task-related activation of these premotor areas was similar in carriers of a Parkin or PINK1 mutation. CONCLUSION: Mutations in different genes linked to recessively inherited Parkinson disease are associated with an additional...

  2. Bioenergetic consequences of PINK1 mutations in Parkinson disease.

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    Andrey Yurevich Abramov

    Full Text Available Mutations of the gene for PTEN-induced kinase 1 (PINK1 are a cause of familial Parkinson's disease (PD. PINK1 protein has been localised to mitochondria and PINK1 gene knockout models exhibit abnormal mitochondrial function. The purpose of this study was to determine whether cells derived from PD patients with a range of PINK1 mutations demonstrate similar defects of mitochondrial function, whether the nature and severity of the abnormalities vary between mutations and correlate with clinical features.We investigated mitochondrial bioenergetics in live fibroblasts from PINK1 mutation patients using single cell techniques. We found that fibroblasts from PINK1 mutation patients had significant defects of bioenergetics including reduced mitochondrial membrane potential, altered redox state, a respiratory deficiency that was determined by substrate availability, and enhanced sensitivity to calcium stimulation and associated mitochondrial permeability pore opening. There was an increase in the basal rate of free radical production in the mutant cells. The pattern and severity of abnormality varied between different mutations, and the less severe defects in these cells were associated with later age of onset of PD.The results provide insight into the molecular pathology of PINK1 mutations in PD and also confirm the critical role of substrate availability in determining the biochemical phenotype--thereby offering the potential for novel therapeutic strategies to circumvent these abnormalities.

  3. Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit

    DEFF Research Database (Denmark)

    Eggers, C; Schmidt, A; Hagenah, J

    2010-01-01

    While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor.......While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor....

  4. The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity.

    Science.gov (United States)

    Ando, Maya; Fiesel, Fabienne C; Hudec, Roman; Caulfield, Thomas R; Ogaki, Kotaro; Górka-Skoczylas, Paulina; Koziorowski, Dariusz; Friedman, Andrzej; Chen, Li; Dawson, Valina L; Dawson, Ted M; Bu, Guojun; Ross, Owen A; Wszolek, Zbigniew K; Springer, Wolfdieter

    2017-04-24

    Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson's disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms. While structure and function of PARKIN variants have been well studied, PINK1 mutations remain poorly characterized, in particular under endogenous conditions. A better understanding of the exact molecular pathogenic mechanisms underlying the pathogenicity is crucial for rational drug design in the future. Here, we characterized the pathogenicity of the PINK1 p.I368N mutation on the clinical and genetic as well as on the structural and functional level in patients' fibroblasts and in cell-based, biochemical assays. Under endogenous conditions, PINK1 p.I368N is expressed, imported, and N-terminally processed in healthy mitochondria similar to PINK1 wild type (WT). Upon mitochondrial damage, however, full-length PINK1 p.I368N is not sufficiently stabilized on the outer mitochondrial membrane (OMM) resulting in loss of mitochondrial quality control. We found that binding of PINK1 p.I368N to the co-chaperone complex HSP90/CDC37 is reduced and stress-induced interaction with TOM40 of the mitochondrial protein import machinery is abolished. Analysis of a structural PINK1 p.I368N model additionally suggested impairments of Ub kinase activity as the ATP-binding pocket was found deformed and the substrate Ub was slightly misaligned within the active site of the kinase. Functional assays confirmed the lack of Ub kinase activity. Here we demonstrated that mutant PINK1 p.I368N can not be stabilized on the OMM upon

  5. The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.

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    Rüediger Hilker

    Full Text Available Mutations in the PINK1 gene cause autosomal recessive familial Parkinson's disease (PD. The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous ((31P and proton ((1H 3-T magnetic resonance spectroscopic imaging (MRSI in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6 compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA positron emission tomography (PET. The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and β-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA K(i values correlated positively with MI (r = 0.879, p<0.001 and inversely with β-ATP (r = -0.784, p = 0.008 and GPC concentrations (r = -0.651, p = 0.030 in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.

  6. Early-onset Parkinson's disease due to PINK1 p.Q456X mutation - clinical and functional study

    Science.gov (United States)

    Siuda, Joanna; Jasinska-Myga, Barbara; Boczarska-Jedynak, Magdalena; Opala, Grzegorz; Fiesel, Fabienne C.; Moussaud-Lamodière, Elisabeth L.; Scarffe, Leslie A.; Dawson, Valina L.; Ross, Owen A.; Springer, Wolfdieter; Dawson, Ted M.; Wszolek, Zbigniew K.

    2014-01-01

    Background Recessive mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause early-onset Parkinson's disease (EOPD). The clinical phenotype of families that have this PINK1-associated disease may present with different symptoms, including typical PD. The loss of the PINK1 protein may lead to mitochondrial dysfunction, which causes dopaminergic neuron death. Methods The clinical phenotypes of a large Polish family with EOPD and an identified PINK1 homozygous nonsense mutation were assessed. Ubiquitination and degradation of mitochondrial parkin substrates as well as mitochondrial bioenergetics were investigated as direct functional readouts for PINK1's kinase activity in biopsied dermal fibroblasts. Results A four-generation family was genealogically evaluated. Genetic screening identified two affected subjects who were both homozygous carriers of the pathogenic PINK1 p.Q456X substitution. Both patients presented with dystonia and gait disorders at symptom onset. Seven heterozygous mutation carriers remained unaffected. Functional studies revealed that the PINK1 p.Q456X protein is non-functional in activating the downstream ubiquitin ligase parkin and priming the ubiquitination of its substrates, and that the RNA levels of PINK1 were significantly reduced. Conclusions The PINK1 p.Q456X mutation leads to a decrease in mRNA and a loss of protein function. The foot dystonia and gait disorders seen at disease onset in affected members of our family, which were accompanied by parkinsonism had a similar clinical presentation to what has been described in previous reports of PINK1 mutation carriers. PMID:25226871

  7. Biological effects of the PINK1 c.1366C>T mutation: implications in Parkinson disease pathogenesis.

    Science.gov (United States)

    Grünewald, Anne; Breedveld, Guido J; Lohmann-Hedrich, Katja; Rohé, Christan F; König, Inke R; Hagenah, Johann; Vanacore, Nicola; Meco, Giuseppe; Antonini, Angelo; Goldwurm, Stefano; Lesage, Suzanne; Dürr, Alexandra; Binkofski, Ferdinand; Siebner, Hartwig; Münchau, Alexander; Brice, Alexis; Oostra, Ben A; Klein, Christine; Bonifati, Vincenzo

    2007-04-01

    PINK1 gene mutations are a cause of recessively inherited, early-onset Parkinson's disease. In some patients, a single heterozygous mutation has been identified, including the recurrent c.1366C>T transition. The interpretation of this finding remains controversial. Furthermore, the c.1366C>T mutation is associated with lower levels of PINK1 transcript, raising the question of whether mRNA levels correlate with the clinical status. We sequenced genomic DNA and copy DNA (cDNA) from 20 subjects carrying the c.1366C>T mutation in the homozygous (n = 5) or heterozygous (n = 15) state. In 17 mutation carriers, messenger RNA (mRNA) was quantified by real-time PCR using four different assays (PINK1 exon 5-6 or exon 7-8 relative to control genes SDHA or YWHAZ). Genomic sequencing confirmed the presence and zygosity of PINK1 mutations. cDNA sequencing in heterozygous mutation carriers revealed a strong wild-type and a much weaker or almost absent mutant signal, whereas in the homozygous patients, only the mutant signal was detected. Homozygous and heterozygous carriers showed PINK1 mRNA levels relative to a reference gene in the range of 0.1-0.2 and 0.5-0.6, respectively, compared with values of 0.9-1.0 in mutation-negative individuals. Treatment of lymphoblasts from a heterozygous mutation carrier with cycloheximide markedly increased the mutant transcript signal. We conclude that the recurrent PINK1 c.1366C>T mutation exerts a major effect at the mRNA level (80-90% reduction), most likely via nonsense-mediated mRNA decay. The absence of correlation between PINK1 mRNA levels and clinical status in heterozygous mutation carriers suggests that other genetic or environmental factors play a role in determining the phenotypic variability associated with the c.1366C>T mutation.

  8. Responsiveness to distracting stimuli, though increased in Parkinson's disease, is decreased in asymptomatic PINK1 and Parkin mutation carriers

    DEFF Research Database (Denmark)

    Verleger, Rolf; Hagenah, Johann; Weiss, Manuel

    2010-01-01

    with the reduced internal motor drive. Of interest in this context is whether responsiveness is already enhanced in the presymptomatic stage of PD. To address these questions, we studied a group of non-manifesting carriers of heterozygous Parkin and PINK1 mutations while they performed a choice-response task...

  9. Structural determinants of PINK1 topology and dual subcellular distribution

    OpenAIRE

    Kang Un; Lin William

    2010-01-01

    Abstract Background PINK1 is a mitochondria-targeted kinase that constitutively localizes to both the mitochondria and the cytosol. The mechanism of how PINK1 achieves cytosolic localization following mitochondrial processing remains unknown. Understanding PINK1 subcellular localization will give us insights into PINK1 functions and how mutations in PINK1 lead to Parkinson's disease. We asked how the mitochondrial localization signal, the transmembrane domain, and the kinase domain participat...

  10. Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations.

    Science.gov (United States)

    Erer, Sevda; Egeli, Unal; Zarifoglu, Mehmet; Tezcan, Gulcin; Cecener, Gulsah; Tunca, Berrin; Ak, Secil; Demirdogen, Elif; Kenangil, Gulay; Kaleagası, Hakan; Dogu, Okan; Saka, Esen; Elibol, Bulent

    2016-09-01

    Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients. All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients. These variants were evaluated using SIFT, PolyPhen, HSF, and LOVD web-based programs. The frequency of EOPD-associated variations in the PRKN gene was 34%. Among these variations, p.A82E in exon 3 and p.Q409X in exon 11 was determined to be pathogenic. We also defined previously unknown cryptic variations, including c.872-35 G>A and c.872-28T>G in exon 8 of PRKN and c.252+30 T>G and c.322+4 A>G in exons 4 and 5 of DJ1, respectively, that were associated with EOPD. Although no significant association was observed between the PARK gene mutations and clinical features (P>0.05), the alterations were related to the clinical symptoms in each patient. An increasing number of studies report that PRKN, PINK1, DJ1 and SNCA mutations are associated with early-onset Parkinson's disease; however, a limited number of studies have been conducted in Turkey. Additionally, our study is the first to evaluate the frequency of SNCA mutations in a Turkish population. The aim of this study was determine the frequency distributions of the PRKN, PINK1, DJ1, and SNCA gene mutations and to analyze the relationships between these genetic variations and the clinical phenotype of EOPD in Turkish patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix.

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    Ruth E Thomas

    Full Text Available Loss-of-function mutations in PINK1, which encodes a mitochondrially targeted serine/threonine kinase, result in an early-onset heritable form of Parkinson's disease. Previous work has shown that PINK1 is constitutively degraded in healthy cells, but selectively accumulates on the surface of depolarized mitochondria, thereby initiating their autophagic degradation. Although PINK1 is known to be a cleavage target of several mitochondrial proteases, whether these proteases account for the constitutive degradation of PINK1 in healthy mitochondria remains unclear. To explore the mechanism by which PINK1 is degraded, we performed a screen for mitochondrial proteases that influence PINK1 abundance in the fruit fly Drosophila melanogaster. We found that genetic perturbations targeting the matrix-localized protease Lon caused dramatic accumulation of processed PINK1 species in several mitochondrial compartments, including the matrix. Knockdown of Lon did not decrease mitochondrial membrane potential or trigger activation of the mitochondrial unfolded protein stress response (UPRmt, indicating that PINK1 accumulation in Lon-deficient animals is not a secondary consequence of mitochondrial depolarization or the UPRmt. Moreover, the influence of Lon on PINK1 abundance was highly specific, as Lon inactivation had little or no effect on the abundance of other mitochondrial proteins. Further studies indicated that the processed forms of PINK1 that accumulate upon Lon inactivation are capable of activating the PINK1-Parkin pathway in vivo. Our findings thus suggest that Lon plays an essential role in regulating the PINK1-Parkin pathway by promoting the degradation of PINK1 in the matrix of healthy mitochondria.

  12. Studies of mutations and polymorphism of PINK1 gene in patients with Parkinson' s disease in littoral of Zhejiang Province%浙江沿海温岭地区帕金森病PINK1基因突变与多态性研究

    Institute of Scientific and Technical Information of China (English)

    郑志华; 仇晨峰; 郑志辉; 林红霞

    2012-01-01

    目的 探讨浙江温岭地区帕金森病( Parkinson's disease,PD)患者PINK1基因突变和多态性分布特点,及其与PD的关系.方法 采用聚合酶链反应扩增200例PD组(早发性PD 112例、晚发性PD 88例)和220名相匹配的对照组(青年对照组68名、老年对照组152名)的PINK1基因1~8号外显子,并对扩增产物进行测序,斑点杂交法检测明确其基因型,计算其基因型频率和等位基因频率,并进行统计学分析.结果 未发现PD组和对照组出现PINK1基因外显子的缺失突变;在早发性PD组中有2例出现5号外显子杂合型突变(G12169A),发现该地区存在PINK1基因5号外显子G12164A,多态有G/G和G/A两种基因型,无A/A基因型,而G12101A多态有G/A和A/A两种基因型,无G/G基因型.PD组的PINK1基因5号外显子G12164A多态在A/A基因型频率84/200(42.0%)与对照组52/220(23.6%)相比有升高趋势(x2=4.034,P=0.045),在晚发性PD组中A/A基因型频率(40/88,45.5%)与老年对照组(32/152,21.1%)相比有升高趋势(x2=3.951,P=0.047),其余各组之间的等位基因频率比较差异均无统计学意义.结论 PINK1基因可能不是浙江温岭地区PD患者致病基因的突变热点;G12164A、G12101A连锁多态才是该地区晚发性PD患者的易患因素.%Objective To study deletion mutations and polymorphism of PINK1 gene exons in patients with Parkinson' s disease (PD) in the littoral of Zhejiang Province,and analyze the association between these changes and the etiology of PD.Methods All exons of PINK1 gene in 200 PD patients( 112early-onset PD and 88 late-onset PD) and 220 controls (68 young controls and 152 old controls ) were amplified by polymerase chain reaction (PCR). All the positive PCR products were sequenced,and genotypes were detected by dot blot allele and genotype frequencies of PINK1 were compared by the Chisquare test.Results No deletion mutations of the exons were found in all patients and controls.However,a known

  13. Aconitase causes iron toxicity in Drosophila pink1 mutants.

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    Giovanni Esposito

    2013-04-01

    Full Text Available The PTEN-induced kinase 1 (PINK1 is a mitochondrial kinase, and pink1 mutations cause early onset Parkinson's disease (PD in humans. Loss of pink1 in Drosophila leads to defects in mitochondrial function, and genetic data suggest that another PD-related gene product, Parkin, acts with pink1 to regulate the clearance of dysfunctional mitochondria (mitophagy. Consequently, pink1 mutants show an accumulation of morphologically abnormal mitochondria, but it is unclear if other factors are involved in pink1 function in vivo and contribute to the mitochondrial morphological defects seen in specific cell types in pink1 mutants. To explore the molecular mechanisms of pink1 function, we performed a genetic modifier screen in Drosophila and identified aconitase (acon as a dominant suppressor of pink1. Acon localizes to mitochondria and harbors a labile iron-sulfur [4Fe-4S] cluster that can scavenge superoxide to release hydrogen peroxide and iron that combine to produce hydroxyl radicals. Using Acon enzymatic mutants, and expression of mitoferritin that scavenges free iron, we show that [4Fe-4S] cluster inactivation, as a result of increased superoxide in pink1 mutants, results in oxidative stress and mitochondrial swelling. We show that [4Fe-4S] inactivation acts downstream of pink1 in a pathway that affects mitochondrial morphology, but acts independently of parkin. Thus our data indicate that superoxide-dependent [4Fe-4S] inactivation defines a potential pathogenic cascade that acts independent of mitophagy and links iron toxicity to mitochondrial failure in a PD-relevant model.

  14. PINK1-Interacting Proteins: Proteomic Analysis of Overexpressed PINK1

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    Aleksandar Rakovic

    2011-01-01

    Full Text Available Recent publications suggest that the Parkinson's disease- (PD- related PINK1/Parkin pathway promotes elimination of dysfunctional mitochondria by autophagy. We used tandem affinity purification (TAP, SDS-PAGE, and mass spectrometry as a first step towards identification of possible substrates for PINK1. The cellular abundance of selected identified interactors was investigated by Western blotting. Furthermore, one candidate gene was sequenced in 46 patients with atypical PD. In addition to two known binding partners (HSP90, CDC37, 12 proteins were identified using the TAP assay; four of which are mitochondrially localized (GRP75, HSP60, LRPPRC, and TUFM. Western blot analysis showed no differences in cellular abundance of these proteins comparing PINK1 mutant and control fibroblasts. When sequencing LRPPRC, four exonic synonymous changes and 20 polymorphisms in noncoding regions were detected. Our study provides a list of putative PINK1 binding partners, confirming previously described interactions, but also introducing novel mitochondrial proteins as potential components of the PINK1/Parkin mitophagy pathway.

  15. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway.

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    Angela C Poole

    Full Text Available Loss-of-function mutations in the PINK1 or parkin genes result in recessive heritable forms of parkinsonism. Genetic studies of Drosophila orthologs of PINK1 and parkin indicate that PINK1, a mitochondrially targeted serine/threonine kinase, acts upstream of Parkin, a cytosolic ubiquitin-protein ligase, to promote mitochondrial fragmentation, although the molecular mechanisms by which the PINK1/Parkin pathway promotes mitochondrial fragmentation are unknown. We tested the hypothesis that PINK1 and Parkin promote mitochondrial fragmentation by targeting core components of the mitochondrial morphogenesis machinery for ubiquitination. We report that the steady-state abundance of the mitochondrial fusion-promoting factor Mitofusin (dMfn is inversely correlated with the activity of PINK1 and Parkin in Drosophila. We further report that dMfn is ubiquitinated in a PINK1- and Parkin-dependent fashion and that dMfn co-immunoprecipitates with Parkin. By contrast, perturbations of PINK1 or Parkin did not influence the steady-state abundance of the mitochondrial fission-promoting factor Drp1 or the mitochondrial fusion-promoting factor Opa1, or the subcellular distribution of Drp1. Our findings suggest that dMfn is a direct substrate of the PINK1/Parkin pathway and that the mitochondrial morphological alterations and tissue degeneration phenotypes that derive from mutations in PINK1 and parkin result at least in part from reduced ubiquitin-mediated turnover of dMfn.

  16. Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance

    NARCIS (Netherlands)

    Heeman, B.; Haute, C. Van den; Aelvoet, S.A.; Valsecchi, F.; Rodenburg, R.J.T.; Reumers, V.; Debyser, Z.; Callewaert, G.; Koopman, W.J.H.; Willems, P.H.G.M.; Baekelandt, V.

    2011-01-01

    Loss-of-function mutations in the gene encoding the mitochondrial PTEN-induced putative kinase 1 (PINK1) are a major cause of early-onset familial Parkinson's disease (PD). Recent studies have highlighted an important function for PINK1 in clearing depolarized mitochondria by mitophagy. However, the

  17. Association of Parkinson disease-related protein PINK1 with Alzheimer disease and multiple sclerosis brain lesions.

    Science.gov (United States)

    Wilhelmus, Micha M M; van der Pol, Susanne M A; Jansen, Quentin; Witte, Maarten E; van der Valk, Paul; Rozemuller, Annemieke J M; Drukarch, Benjamin; de Vries, Helga E; Van Horssen, Jack

    2011-02-01

    Mitochondrial dysfunction and oxidative stress are hallmarks of various neurological disorders, including multiple sclerosis (MS), Alzheimer disease (AD), and Parkinson disease (PD). Mutations in PINK1, a mitochondrial kinase, have been linked to the occurrence of early onset parkinsonism. Currently, various studies support the notion of a neuroprotective role for PINK1, as it protects cells from stress-mediated mitochondrial dysfunction, oxidative stress, and apoptosis. Because information about the distribution pattern of PINK1 in neurological diseases other than PD is scarce, we here investigated PINK1 expression in well-characterized brain samples derived from MS and AD individuals using immunohistochemistry. In control gray matter PINK1 immunoreactivity was observed in neurons, particularly neurons in layers IV-VI. Astrocytes were the most prominent cell type decorated by anti-PINK1 antibody in the white matter. In addition, PINK1 staining was observed in the cerebrovasculature. In AD, PINK1 was found to colocalize with classic senile plaques and vascular amyloid depositions, as well as reactive astrocytes associated with the characteristic AD lesions. Interestingly, PINK1 was absent from neurofibrillary tangles. In active demyelinating MS lesions we observed a marked astrocytic PINK1 immunostaining, whereas astrocytes in chronic lesions were weakly stained. Taken together, we observed PINK1 immunostaining in both AD and MS lesions, predominantly in reactive astrocytes associated with these lesions, suggesting that the increase in astrocytic PINK1 protein might be an intrinsic protective mechanism to limit cellular injury. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Loss of PINK1 impairs stress-induced autophagy and cell survival.

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    Dajana Parganlija

    Full Text Available The mitochondrial kinase PINK1 and the ubiquitin ligase Parkin are participating in quality control after CCCP- or ROS-induced mitochondrial damage, and their dysfunction is associated with the development and progression of Parkinson's disease. Furthermore, PINK1 expression is also induced by starvation indicating an additional role for PINK1 in stress response. Therefore, the effects of PINK1 deficiency on the autophago-lysosomal pathway during stress were investigated. Under trophic deprivation SH-SY5Y cells with stable PINK1 knockdown showed downregulation of key autophagic genes, including Beclin, LC3 and LAMP-2. In good agreement, protein levels of LC3-II and LAMP-2 but not of LAMP-1 were reduced in different cell model systems with PINK1 knockdown or knockout after addition of different stressors. This downregulation of autophagic factors caused increased apoptosis, which could be rescued by overexpression of LC3 or PINK1. Taken together, the PINK1-mediated reduction of autophagic key factors during stress resulted in increased cell death, thus defining an additional pathway that could contribute to the progression of Parkinson's disease in patients with PINK1 mutations.

  19. PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin

    Science.gov (United States)

    Narendra, Derek P.; Jin, Seok Min; Tanaka, Atsushi; Suen, Der-Fen; Gautier, Clement A.; Shen, Jie; Cookson, Mark R.; Youle, Richard J.

    2010-01-01

    Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination. PMID:20126261

  20. Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria.

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    Song Liu

    Full Text Available Mutations in Pten-induced kinase 1 (PINK1 are linked to early-onset familial Parkinson's disease (FPD. PINK1 has previously been implicated in mitochondrial fission/fusion dynamics, quality control, and electron transport chain function. However, it is not clear how these processes are interconnected and whether they are sufficient to explain all aspects of PINK1 pathogenesis. Here we show that PINK1 also controls mitochondrial motility. In Drosophila, downregulation of dMiro or other components of the mitochondrial transport machinery rescued dPINK1 mutant phenotypes in the muscle and dopaminergic (DA neurons, whereas dMiro overexpression alone caused DA neuron loss. dMiro protein level was increased in dPINK1 mutant but decreased in dPINK1 or dParkin overexpression conditions. In Drosophila larval motor neurons, overexpression of dPINK1 inhibited axonal mitochondria transport in both anterograde and retrograde directions, whereas dPINK1 knockdown promoted anterograde transport. In HeLa cells, overexpressed hPINK1 worked together with hParkin, another FPD gene, to regulate the ubiquitination and degradation of hMiro1 and hMiro2, apparently in a Ser-156 phosphorylation-independent manner. Also in HeLa cells, loss of hMiro promoted the perinuclear clustering of mitochondria and facilitated autophagy of damaged mitochondria, effects previously associated with activation of the PINK1/Parkin pathway. These newly identified functions of PINK1/Parkin and Miro in mitochondrial transport and mitophagy contribute to our understanding of the complex interplays in mitochondrial quality control that are critically involved in PD pathogenesis, and they may explain the peripheral neuropathy symptoms seen in some PD patients carrying particular PINK1 or Parkin mutations. Moreover, the different effects of loss of PINK1 function on Miro protein level in Drosophila and mouse cells may offer one explanation of the distinct phenotypic manifestations of PINK1

  1. Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease

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    Susann Lehmann

    2017-02-01

    Full Text Available Familial forms of Parkinson's disease (PD caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD+ is essential for both generating energy in mitochondria and nuclear DNA repair through NAD+-consuming poly(ADP-ribose polymerases (PARPs. We found alterations in NAD+ salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD+ precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration. Additionally, a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants. We conclude that enhancing the availability of NAD+ by either the use of a diet supplemented with NAD+ precursors or the inhibition of NAD+-dependent enzymes, such as PARPs, which compete with mitochondria for NAD+, is a viable approach to preventing neurotoxicity associated with mitochondrial defects.

  2. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65

    Science.gov (United States)

    Kondapalli, Chandana; Kazlauskaite, Agne; Zhang, Ning; Woodroof, Helen I.; Campbell, David G.; Gourlay, Robert; Burchell, Lynn; Walden, Helen; Macartney, Thomas J.; Deak, Maria; Knebel, Axel; Alessi, Dario R.; Muqit, Miratul M. K.

    2012-01-01

    Summary Missense mutations in PTEN-induced kinase 1 (PINK1) cause autosomal-recessive inherited Parkinson's disease (PD). We have exploited our recent discovery that recombinant insect PINK1 is catalytically active to test whether PINK1 directly phosphorylates 15 proteins encoded by PD-associated genes as well as proteins reported to bind PINK1. We have discovered that insect PINK1 efficiently phosphorylates only one of these proteins, namely the E3 ligase Parkin. We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser65. We show that human PINK1 is specifically activated by mitochondrial membrane potential (Δψm) depolarization, enabling it to phosphorylate Parkin at Ser65. We further show that phosphorylation of Parkin at Ser65 leads to marked activation of its E3 ligase activity that is prevented by mutation of Ser65 or inactivation of PINK1. We provide evidence that once activated, PINK1 autophosphorylates at several residues, including Thr257, which is accompanied by an electrophoretic mobility band-shift. These results provide the first evidence that PINK1 is activated following Δψm depolarization and suggest that PINK1 directly phosphorylates and activates Parkin. Our findings indicate that monitoring phosphorylation of Parkin at Ser65 and/or PINK1 at Thr257 represent the first biomarkers for examining activity of the PINK1-Parkin signalling pathway in vivo. Our findings also suggest that small molecule activators of Parkin that mimic the effect of PINK1 phosphorylation may confer therapeutic benefit for PD. PMID:22724072

  3. Oxidative stress and regulation of Pink1 in zebrafish (Danio rerio.

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    Madhusmita Priyadarshini

    Full Text Available Oxidative stress-mediated neuronal dysfunction is characteristic of several neurodegenerative disorders, including Parkinson's disease (PD. The enzyme tyrosine hydroxylase (TH catalyzes the formation of L-DOPA, the rate-limiting step in the biosynthesis of dopamine. A lack of dopamine in the striatum is the most characteristic feature of PD, and the cause of the most dominant symptoms. Loss of function mutations in the PTEN-induced putative kinase (PINK1 gene cause autosomal recessive PD. This study explored the basic mechanisms underlying the involvement of pink1 in oxidative stress-mediated PD pathology using zebrafish as a tool. We generated a transgenic line, Tg(pink1:EGFP, and used it to study the effect of oxidative stress (exposure to H2O2 on pink1 expression. GFP expression was enhanced throughout the brain of zebrafish larvae subjected to oxidative stress. In addition to a widespread increase in pink1 mRNA expression, mild oxidative stress induced a clear decline in tyrosine hydroxylase 2 (th2, but not tyrosine hydroxylase 1 (th1 expression, in the brain of wild-type larvae. The drug L-Glutathione Reduced (LGR has been associated with anti-oxidative and possible neuroprotective properties. Administration of LGR normalized the increased fluorescence intensity indicating pink1 transgene expression and endogenous pink1 mRNA expression in larvae subjected to oxidative stress by H2O2. In the pink1 morpholino oliogonucleotide-injected larvae, the reduction in the expression of th1 and th2 was partially rescued by LGR. The pink1 gene is a sensitive marker of oxidative stress in zebrafish, and LGR effectively normalizes the consequences of mild oxidative stress, suggesting that the neuroprotective effects of pink1 and LGR may be significant and useful in drug development.

  4. (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation

    Science.gov (United States)

    Fiesel, Fabienne C; Ando, Maya; Hudec, Roman; Hill, Anneliese R; Castanedes-Casey, Monica; Caulfield, Thomas R; Moussaud-Lamodière, Elisabeth L; Stankowski, Jeannette N; Bauer, Peter O; Lorenzo-Betancor, Oswaldo; Ferrer, Isidre; Arbelo, José M; Siuda, Joanna; Chen, Li; Dawson, Valina L; Dawson, Ted M; Wszolek, Zbigniew K; Ross, Owen A; Dickson, Dennis W; Springer, Wolfdieter

    2015-01-01

    Mutations in PINK1 and PARKIN cause recessive, early-onset Parkinson’s disease (PD). Together, these two proteins orchestrate a protective mitophagic response that ensures the safe disposal of damaged mitochondria. The kinase PINK1 phosphorylates ubiquitin (Ub) at the conserved residue S65, in addition to modifying the E3 ubiquitin ligase Parkin. The structural and functional consequences of Ub phosphorylation (pS65-Ub) have already been suggested from in vitro experiments, but its (patho-)physiological significance remains unknown. We have generated novel antibodies and assessed pS65-Ub signals in vitro and in cells, including primary neurons, under endogenous conditions. pS65-Ub is dependent on PINK1 kinase activity as confirmed in patient fibroblasts and postmortem brain samples harboring pathogenic mutations. We show that pS65-Ub is reversible and barely detectable under basal conditions, but rapidly induced upon mitochondrial stress in cells and amplified in the presence of functional Parkin. pS65-Ub accumulates in human brain during aging and disease in the form of cytoplasmic granules that partially overlap with mitochondrial, lysosomal, and total Ub markers. Additional studies are now warranted to further elucidate pS65-Ub functions and fully explore its potential for biomarker or therapeutic development. PMID:26162776

  5. Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1.

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    Anna Sandebring

    Full Text Available PTEN-induced novel kinase 1 (PINK1 mutations are associated with autosomal recessive parkinsonism. Previous studies have shown that PINK1 influences both mitochondrial function and morphology although it is not clearly established which of these are primary events and which are secondary. Here, we describe a novel mechanism linking mitochondrial dysfunction and alterations in mitochondrial morphology related to PINK1. Cell lines were generated by stably transducing human dopaminergic M17 cells with lentiviral constructs that increased or knocked down PINK1. As in previous studies, PINK1 deficient cells have lower mitochondrial membrane potential and are more sensitive to the toxic effects of mitochondrial complex I inhibitors. We also show that wild-type PINK1, but not recessive mutant or kinase dead versions, protects against rotenone-induced mitochondrial fragmentation whereas PINK1 deficient cells show lower mitochondrial connectivity. Expression of dynamin-related protein 1 (Drp1 exaggerates PINK1 deficiency phenotypes and Drp1 RNAi rescues them. We also show that Drp1 is dephosphorylated in PINK1 deficient cells due to activation of the calcium-dependent phosphatase calcineurin. Accordingly, the calcineurin inhibitor FK506 blocks both Drp1 dephosphorylation and loss of mitochondrial integrity in PINK1 deficient cells but does not fully rescue mitochondrial membrane potential. We propose that alterations in mitochondrial connectivity in this system are secondary to functional effects on mitochondrial membrane potential.

  6. PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival

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    Yunjong Lee

    2017-01-01

    Full Text Available Mutations in PTEN-induced putative kinase 1 (PINK1 and parkin cause autosomal-recessive Parkinson’s disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746 that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. PINK1 phosphorylation of PARIS alleviates PARIS toxicity, as well as repression of PGC-1α promoter activity. Conditional knockdown of PINK1 in adult mouse brains leads to a progressive loss of dopaminergic neurons in the substantia nigra that is dependent on PARIS. Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival.

  7. The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function

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    Wahlestedt Claes

    2007-03-01

    Full Text Available Abstract Background Mutations in the PTEN induced putative kinase 1 (PINK1 are implicated in early-onset Parkinson's disease. PINK1 is expressed abundantly in mitochondria rich tissues, such as skeletal muscle, where it plays a critical role determining mitochondrial structural integrity in Drosophila. Results Herein we characterize a novel splice variant of PINK1 (svPINK1 that is homologous to the C-terminus regulatory domain of the protein kinase. Naturally occurring non-coding antisense provides sophisticated mechanisms for diversifying genomes and we describe a human specific non-coding antisense expressed at the PINK1 locus (naPINK1. We further demonstrate that PINK1 varies in vivo when human skeletal muscle mitochondrial content is enhanced, supporting the idea that PINK1 has a physiological role in mitochondrion. The observation of concordant regulation of svPINK1 and naPINK1 during in vivo mitochondrial biogenesis was confirmed using RNAi, where selective targeting of naPINK1 results in loss of the PINK1 splice variant in neuronal cell lines. Conclusion Our data presents the first direct observation that a mammalian non-coding antisense molecule can positively influence the abundance of a cis-transcribed mRNA under physiological abundance conditions. While our analysis implies a possible human specific and dsRNA-mediated mechanism for stabilizing the expression of svPINK1, it also points to a broader genomic strategy for regulating a human disease locus and increases the complexity through which alterations in the regulation of the PINK1 locus could occur.

  8. Heterozygous PINK1 p.G411S increases risk of Parkinson's disease via a dominant-negative mechanism.

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    Puschmann, Andreas; Fiesel, Fabienne C; Caulfield, Thomas R; Hudec, Roman; Ando, Maya; Truban, Dominika; Hou, Xu; Ogaki, Kotaro; Heckman, Michael G; James, Elle D; Swanberg, Maria; Jimenez-Ferrer, Itzia; Hansson, Oskar; Opala, Grzegorz; Siuda, Joanna; Boczarska-Jedynak, Magdalena; Friedman, Andrzej; Koziorowski, Dariusz; Aasly, Jan O; Lynch, Timothy; Mellick, George D; Mohan, Megha; Silburn, Peter A; Sanotsky, Yanosh; Vilariño-Güell, Carles; Farrer, Matthew J; Chen, Li; Dawson, Valina L; Dawson, Ted M; Wszolek, Zbigniew K; Ross, Owen A; Springer, Wolfdieter

    2017-01-01

    SEE GANDHI AND PLUN-FAVREAU DOI101093/AWW320 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: It has been postulated that heterozygous mutations in recessive Parkinson's genes may increase the risk of developing the disease. In particular, the PTEN-induced putative kinase 1 (PINK1) p.G411S (c.1231G>A, rs45478900) mutation has been reported in families with dominant inheritance patterns of Parkinson's disease, suggesting that it might confer a sizeable disease risk when present on only one allele. We examined families with PINK1 p.G411S and conducted a genetic association study with 2560 patients with Parkinson's disease and 2145 control subjects. Heterozygous PINK1 p.G411S mutations markedly increased Parkinson's disease risk (odds ratio = 2.92, P = 0.032); significance remained when supplementing with results from previous studies on 4437 additional subjects (odds ratio = 2.89, P = 0.027). We analysed primary human skin fibroblasts and induced neurons from heterozygous PINK1 p.G411S carriers compared to PINK1 p.Q456X heterozygotes and PINK1 wild-type controls under endogenous conditions. While cells from PINK1 p.Q456X heterozygotes showed reduced levels of PINK1 protein and decreased initial kinase activity upon mitochondrial damage, stress-response was largely unaffected over time, as expected for a recessive loss-of-function mutation. By contrast, PINK1 p.G411S heterozygotes showed no decrease of PINK1 protein levels but a sustained, significant reduction in kinase activity. Molecular modelling and dynamics simulations as well as multiple functional assays revealed that the p.G411S mutation interferes with ubiquitin phosphorylation by wild-type PINK1 in a heterodimeric complex. This impairs the protective functions of the PINK1/parkin-mediated mitochondrial quality control. Based on genetic and clinical evaluation as well as functional and structural characterization, we established p.G411S as a rare genetic risk factor with a relatively large effect size conferred

  9. ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts.

    Science.gov (United States)

    Qi, Yongmei; Qiu, Qian; Gu, Xueyan; Tian, Yihong; Zhang, Yingmei

    2016-04-19

    The ATM (ataxia telangiectasia mutated) protein has recently been proposed to play critical roles in the response to mitochondrial dysfunction by initiating mitophagy. Here, we have used ATM-proficient GM00637 cells and ATM-deficient GM05849 cells to investigate the mitophagic effect of spermidine and to elucidate the role of ATM in spermdine-induced mitophagy. Our results indicate that spermidine induces mitophagy by eliciting mitochondrial depolarization, which triggers the formation of mitophagosomes and mitolysosomes, thereby promoting the accumulation of PINK1 and translocation of Parkin to damaged mitochondria, finally leading to the decreased mitochondrial mass in GM00637 cells. However, in GM05849 cells or GM00637 cells pretreated with the ATM kinase inhibitor KU55933, the expression of full-length PINK1 and the translocation of Parkin are blocked, and the colocalization of Parkin with either LC3 or PINK1 is disrupted. These results suggest that ATM drives the initiation of the mitophagic cascade. Our study demonstrates that spermidine induces mitophagy through ATM-dependent activation of the PINK1/Parkin pathway. These findings underscore the importance of a mitophagy regulatory network of ATM and PINK1/Parkin and elucidate a novel mechanism by which ATM influences spermidine-induced mitophagy.

  10. Formation of parkin aggregates and enhanced PINK1 accumulation during the pathogenesis of Parkinson's disease.

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    Um, Ji Won; Park, Hyun Jung; Song, Jihwan; Jeon, Iksoo; Lee, Gwang; Lee, Phil Hyu; Chung, Kwang Chul

    2010-03-19

    Parkinson's disease (PD) is a devastating neurodegenerative disease characterized by a distinct set of motor symptoms. Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) or parkin have been linked to early-onset autosomal recessive forms of familial PD. We have recently shown that parkin (an E3 ubiquitin ligase) and PINK1 (a serine/threonine kinase) affect one other's stability, solubility, and tendency to form cytoprotective aggresomes (Um et al., 2009). Here we validated the functional relevance of this mutual interaction under pathologic PD conditions, by investigating the changes of expression and solubility of these factors in response to PD-linked toxins. Consistent with our previous cell culture data, exposure of human dopaminergic neuroblastoma SH-SY5Y cells to PD-linked toxins (1-methyl-4-phenylpyridinium ion, 6-hydroxydopamine, or MG132) reduced Nonidet P-40-soluble parkin levels and induced PINK1 accumulation. Consistent with our previous findings from parkin knockout mice, rat models of PD (6-hydroxydopamine-, rotenone-, or MG132-induced PD) were also associated with an increase in soluble and insoluble PINK1 levels as well as enhanced formation of parkin aggregates. These findings suggest that both PINK1 and parkin play important roles in regulating the formation of Lewy bodies during the pathogenesis of sporadic and familial PD.

  11. Loss of PINK1 attenuates HIF-1α induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia.

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    Lin, William; Wadlington, Natasha L; Chen, Linan; Zhuang, Xiaoxi; Brorson, James R; Kang, Un Jung

    2014-02-19

    Parkinson's disease (PD) has multiple proposed etiologies with implication of abnormalities in cellular homeostasis ranging from proteostasis to mitochondrial dynamics to energy metabolism. PINK1 mutations are associated with familial PD and here we discover a novel PINK1 mechanism in cellular stress response. Using hypoxia as a physiological trigger of oxidative stress and disruption in energy metabolism, we demonstrate that PINK1(-/-) mouse cells exhibited significantly reduced induction of HIF-1α protein, HIF-1α transcriptional activity, and hypoxia-responsive gene upregulation. Loss of PINK1 impairs both hypoxia-induced 4E-BP1 dephosphorylation and increase in the ratio of internal ribosomal entry site (IRES)-dependent to cap-dependent translation. These data suggest that PINK1 mediates adaptive responses by activating IRES-dependent translation, and the impairments in translation and the HIF-1α pathway may contribute to PINK1-associated PD pathogenesis that manifests under cellular stress.

  12. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.

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    Suzana Gispert

    Full Text Available BACKGROUND: Parkinson's disease (PD is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1 cause the recessive PARK6 variant of PD. METHODOLOGY/PRINCIPAL FINDINGS: Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. CONCLUSION: Thus, aging Pink1(-/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.

  13. The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function

    DEFF Research Database (Denmark)

    Scheele, Camilla; Petrovic, Natasa; Faghihi, Mohammad A

    2007-01-01

    BACKGROUND: Mutations in the PTEN induced putative kinase 1 (PINK1) are implicated in early-onset Parkinson's disease. PINK1 is expressed abundantly in mitochondria rich tissues, such as skeletal muscle, where it plays a critical role determining mitochondrial structural integrity in Drosophila...

  14. The complex I subunit NDUFA10 selectively rescues Drosophila pink1 mutants through a mechanism independent of mitophagy.

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    Joe H Pogson

    2014-11-01

    Full Text Available Mutations in PINK1, a mitochondrially targeted serine/threonine kinase, cause autosomal recessive Parkinson's disease (PD. Substantial evidence indicates that PINK1 acts with another PD gene, parkin, to regulate mitochondrial morphology and mitophagy. However, loss of PINK1 also causes complex I (CI deficiency, and has recently been suggested to regulate CI through phosphorylation of NDUFA10/ND42 subunit. To further explore the mechanisms by which PINK1 and Parkin influence mitochondrial integrity, we conducted a screen in Drosophila cells for genes that either phenocopy or suppress mitochondrial hyperfusion caused by pink1 RNAi. Among the genes recovered from this screen was ND42. In Drosophila pink1 mutants, transgenic overexpression of ND42 or its co-chaperone sicily was sufficient to restore CI activity and partially rescue several phenotypes including flight and climbing deficits and mitochondrial disruption in flight muscles. Here, the restoration of CI activity and partial rescue of locomotion does not appear to have a specific requirement for phosphorylation of ND42 at Ser-250. In contrast to pink1 mutants, overexpression of ND42 or sicily failed to rescue any Drosophila parkin mutant phenotypes. We also find that knockdown of the human homologue, NDUFA10, only minimally affecting CCCP-induced mitophagy, and overexpression of NDUFA10 fails to restore Parkin mitochondrial-translocation upon PINK1 loss. These results indicate that the in vivo rescue is due to restoring CI activity rather than promoting mitophagy. Our findings support the emerging view that PINK1 plays a role in regulating CI activity separate from its role with Parkin in mitophagy.

  15. Dopamine Induced Neurodegeneration in a PINK1 Model of Parkinson's Disease

    Science.gov (United States)

    Yao, Zhi; Duchen, Michael R.; Wood, Nicholas W.; Abramov, Andrey Y.

    2012-01-01

    Background Parkinson's disease is a common neurodegenerative disease characterised by progressive loss of dopaminergic neurons, leading to dopamine depletion in the striatum. Mutations in the PINK1 gene cause an autosomal recessive form of Parkinson's disease. Loss of PINK1 function causes mitochondrial dysfunction, increased reactive oxygen species production and calcium dysregulation, which increases susceptibility to neuronal death in Parkinson's disease. The basis of neuronal vulnerability to dopamine in Parkinson's disease is not well understood. Methodology We investigated the mechanism of dopamine induced cell death in transgenic PINK1 knockout mouse neurons. We show that dopamine results in mitochondrial depolarisation caused by mitochondrial permeability transition pore (mPTP) opening. Dopamine-induced mPTP opening is dependent on a complex of reactive oxygen species production and calcium signalling. Dopamine-induced mPTP opening, and dopamine-induced cell death, could be prevented by inhibition of reactive oxygen species production, by provision of respiratory chain substrates, and by alteration in calcium signalling. Conclusions These data demonstrate the mechanism of dopamine toxicity in PINK1 deficient neurons, and suggest potential therapeutic strategies for neuroprotection in Parkinson's disease. PMID:22662171

  16. Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation.

    Science.gov (United States)

    Aguirre, Jacob D; Dunkerley, Karen M; Mercier, Pascal; Shaw, Gary S

    2017-01-10

    Mutations in PARK2 and PARK6 genes are responsible for the majority of hereditary Parkinson's disease cases. These genes encode the E3 ubiquitin ligase parkin and the protein kinase PTEN-induced kinase 1 (PINK1), respectively. Together, parkin and PINK1 regulate the mitophagy pathway, which recycles damaged mitochondria following oxidative stress. Native parkin is inactive and exists in an autoinhibited state mediated by its ubiquitin-like (UBL) domain. PINK1 phosphorylation of serine 65 in parkin's UBL and serine 65 of ubiquitin fully activate ubiquitin ligase activity; however, a structural rationale for these observations is not clear. Here, we report the structure of the phosphorylated UBL domain from parkin. We find that destabilization of the UBL results from rearrangements to hydrophobic core packing that modify its structure. Altered surface electrostatics from the phosphoserine group disrupt its intramolecular association, resulting in poorer autoinhibition in phosphorylated parkin. Further, we show that phosphorylation of both the UBL domain and ubiquitin are required to activate parkin by releasing the UBL domain, forming an extended structure needed to facilitate E2-ubiquitin binding. Together, the results underscore the importance of parkin activation by the PINK1 phosphorylation signal and provide a structural picture of the unraveling of parkin's ubiquitin ligase potential.

  17. Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin.

    Science.gov (United States)

    Lazarou, Michael; Jin, Seok Min; Kane, Lesley A; Youle, Richard J

    2012-02-14

    Mutations in the mitochondrial kinase PINK1 and the cytosolic E3 ligase Parkin can cause Parkinson's disease. Damaged mitochondria accumulate PINK1 on the outer membrane where, dependent on kinase activity, it recruits and activates Parkin to induce mitophagy, potentially maintaining organelle fidelity. How PINK1 recruits Parkin is unknown. We show that endogenous PINK1 forms a 700 kDa complex with the translocase of the outer membrane (TOM) selectively on depolarized mitochondria whereas PINK1 ectopically targeted to the outer membrane retains association with TOM on polarized mitochondria. Inducibly targeting PINK1 to peroxisomes or lysosomes, which lack a TOM complex, recruits Parkin and activates ubiquitin ligase activity on the respective organelles. Once there, Parkin induces organelle selective autophagy of peroxisomes but not lysosomes. We propose that the association of PINK1 with the TOM complex allows rapid reimport of PINK1 to rescue repolarized mitochondria from mitophagy, and discount mitochondrial-specific factors for Parkin translocation and activation. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells.

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    Matthew E Gegg

    Full Text Available BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD. Impairment of the mitochondrial electron transport chain (ETC and an increased frequency in deletions of mitochondrial DNA (mtDNA, which encodes some of the subunits of the ETC, have been reported in the substantia nigra of PD brains. The identification of mutations in the PINK1 gene, which cause an autosomal recessive form of PD, has supported mitochondrial involvement in PD. The PINK1 protein is a serine/threonine kinase localized in mitochondria and the cytosol. Its precise function is unknown, but it is involved in neuroprotection against a variety of stress signalling pathways. METHODOLOGY/PRINCIPAL FINDINGS: In this report we have investigated the effect of silencing PINK1 expression in human dopaminergic SH-SY5Y cells by siRNA on mtDNA synthesis and ETC function. Loss of PINK1 expression resulted in a decrease in mtDNA levels and mtDNA synthesis. We also report a concomitant loss of mitochondrial membrane potential and decreased mitochondrial ATP synthesis, with the activity of complex IV of the ETC most affected. This mitochondrial dysfunction resulted in increased markers of oxidative stress under basal conditions and increased cell death following treatment with the free radical generator paraquat. CONCLUSIONS: This report highlights a novel function of PINK1 in mitochondrial biogenesis and a role in maintaining mitochondrial ETC activity. Dysfunction of both has been implicated in sporadic forms of PD suggesting that these may be key pathways in the development of the disease.

  19. The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance.

    Science.gov (United States)

    Bertolin, Giulia; Ferrando-Miguel, Rosa; Jacoupy, Maxime; Traver, Sabine; Grenier, Karl; Greene, Andrew W; Dauphin, Aurélien; Waharte, François; Bayot, Aurélien; Salamero, Jean; Lombès, Anne; Bulteau, Anne-Laure; Fon, Edward A; Brice, Alexis; Corti, Olga

    2013-11-01

    Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD). The cytosolic E3 ubiquitin-protein ligase PARK2 cooperates with the mitochondrial kinase PINK1 to maintain mitochondrial quality. A loss of mitochondrial transmembrane potential (ΔΨ) leads to the PINK1-dependent recruitment of PARK2 to the outer mitochondrial membrane (OMM), followed by the ubiquitination and proteasome-dependent degradation of OMM proteins, and by the autophagy-dependent clearance of mitochondrial remnants. We showed here that blockade of mitochondrial protein import triggers the recruitment of PARK2, by PINK1, to the TOMM machinery. PD-causing PARK2 mutations weakened or disrupted the molecular interaction between PARK2 and specific TOMM subunits: the surface receptor, TOMM70A, and the channel protein, TOMM40. The downregulation of TOMM40 or its associated core subunit, TOMM22, was sufficient to trigger OMM protein clearance in the absence of PINK1 or PARK2. However, PARK2 was required to promote the degradation of whole organelles by autophagy. Furthermore, the overproduction of TOMM22 or TOMM40 reversed mitochondrial clearance promoted by PINK1 and PARK2 after ΔΨ loss. These results indicated that the TOMM machinery is a key molecular switch in the mitochondrial clearance program controlled by the PINK1-PARK2 pathway. Loss of functional coupling between mitochondrial protein import and the neuroprotective degradation of dysfunctional mitochondria may therefore be a primary pathogenic mechanism in autosomal recessive PD.

  20. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65

    Science.gov (United States)

    Kazlauskaite, Agne; Kondapalli, Chandana; Gourlay, Robert; Campbell, David G.; Ritorto, Maria Stella; Hofmann, Kay; Alessi, Dario R.; Knebel, Axel; Trost, Matthias; Muqit, Miratul M. K.

    2014-01-01

    We have previously reported that the Parkinson's disease-associated kinase PINK1 (PTEN-induced putative kinase 1) is activated by mitochondrial depolarization and stimulates the Parkin E3 ligase by phosphorylating Ser65 within its Ubl (ubiquitin-like) domain. Using phosphoproteomic analysis, we identified a novel ubiquitin phosphopeptide phosphorylated at Ser65 that was enriched 14-fold in HEK (human embryonic kidney)-293 cells overexpressing wild-type PINK1 stimulated with the mitochondrial uncoupling agent CCCP (carbonyl cyanide m-chlorophenylhydrazone), to activate PINK1, compared with cells expressing kinase-inactive PINK1. Ser65 in ubiquitin lies in a similar motif to Ser65 in the Ubl domain of Parkin. Remarkably, PINK1 directly phosphorylates Ser65 of ubiquitin in vitro. We undertook a series of experiments that provide striking evidence that Ser65-phosphorylated ubiquitin (ubiquitinPhospho−Ser65) functions as a critical activator of Parkin. First, we demonstrate that a fragment of Parkin lacking the Ubl domain encompassing Ser65 (ΔUbl-Parkin) is robustly activated by ubiquitinPhospho−Ser65, but not by non-phosphorylated ubiquitin. Secondly, we find that the isolated Parkin Ubl domain phosphorylated at Ser65 (UblPhospho−Ser65) can also activate ΔUbl-Parkin similarly to ubiquitinPhospho−Ser65. Thirdly, we establish that ubiquitinPhospho−Ser65, but not non-phosphorylated ubiquitin or UblPhospho−Ser65, activates full-length wild-type Parkin as well as the non-phosphorylatable S65A Parkin mutant. Fourthly, we provide evidence that optimal activation of full-length Parkin E3 ligase is dependent on PINK1-mediated phosphorylation of both Parkin at Ser65 and ubiquitin at Ser65, since only mutation of both proteins at Ser65 completely abolishes Parkin activation. In conclusion, the findings of the present study reveal that PINK1 controls Parkin E3 ligase activity not only by phosphorylating Parkin at Ser65, but also by phosphorylating ubiquitin at Ser65

  1. PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson’s Disease Pathobiology?

    Science.gov (United States)

    Truban, Dominika; Hou, Xu; Caulfield, Thomas R.; Fiesel, Fabienne C.; Springer, Wolfdieter

    2016-01-01

    The first clinical description of Parkinson’s disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy. It has become evident that there are many other aspects of this complex regulated, multifaceted pathway that provides neuroprotection. As such, numerous additional factors that impact PINK1/Parkin have already been identified including genes involved in other forms of PD. A great pathogenic overlap amongst different forms of familial, environmental and even sporadic disease is emerging that potentially converges at the level of mitochondrial quality control. Tremendous efforts now seek to further detail the roles and exploit PINK1 and Parkin, their upstream regulators and downstream signaling pathways for future translation. This review summarizes the latest findings on PINK1/Parkin-directed mitochondrial quality control, its integration and cross-talk with other disease factors and pathways as well as the implications for idiopathic PD. In addition, we highlight novel avenues for the development of biomarkers and disease-modifying therapies that are based on a detailed understanding of the PINK1/Parkin pathway. PMID:27911343

  2. Parkin and PINK1: Much More than Mitophagy

    Science.gov (United States)

    Scarffe, Leslie A.; Stevens, Daniel A.; Dawson, Valina L.; Dawson, Ted M.

    2014-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes a debilitating movement disorder. While most cases of PD appear to be sporadic, rare Mendelian forms have provided tremendous insight into disease pathogenesis. Accumulating evidence suggests that impaired mitochondria underpin PD pathology. In support of this theory, data from multiple PD models has linked PINK1 and parkin, two recessive PD genes, in a common pathway impacting mitochondrial health, prompting a flurry of research to identify their mitochondrial targets. Recent work has focused on the role of PINK1 and parkin in mediating mitochondrial autophagy (mitophagy), however, emerging evidence casts parkin and PINK1 as key players in multiple domains of mitochondrial health and quality control. PMID:24735649

  3. PINK1/Parkin-mediated mitophagy in mammalian cells.

    Science.gov (United States)

    Eiyama, Akinori; Okamoto, Koji

    2015-04-01

    Mitochondria-specific autophagy (mitophagy) is a fundamental process critical for maintaining mitochondrial fitness in a myriad of cell types. Particularly, mitophagy contributes to mitochondrial quality control by selectively eliminating dysfunctional mitochondria. In mammalian cells, the Ser/Thr kinase PINK1 and the E3 ubiquitin ligase Parkin act cooperatively in sensing mitochondrial functional state and marking damaged mitochondria for disposal via the autophagy pathway. Notably, ubiquitin and deubiquitinases play vital roles in modulating Parkin activity and mitophagy efficiency. In this review, we highlight recent breakthroughs addressing the key issues of how PINK1 activates Parkin in response to mitochondrial malfunction, how Parkin localizes specifically to impaired mitochondria, and how ubiquitination and deubiquitination regulate PINK1/Parkin-mediated mitophagy.

  4. Loss-of-function rodent models for parkin and PINK1.

    Science.gov (United States)

    Oliveras-Salvá, Marusela; Van Rompuy, Anne-Sophie; Heeman, Bavo; Van den Haute, Chris; Baekelandt, Veerle

    2011-01-01

    Parkinson's disease is a common neurodegenerative disorder whose aetiology is not yet fully understood. In the past ten years, the discovery of genes linked to hereditary forms of the disease has impelled the development of animal models. These should lead to the identification of novel pathways that provide insight into the functionality of the proteins involved and the pathogenesis of the sporadic forms of the disease. In particular, loss-of-function mutations in the parkin and PINK1 (phosphatase and tensin homolog (PTEN)-induced kinase 1) genes account for most of the cases of familial autosomal recessive parkinsonism. Both parkin and PINK1 knockout rodent models are now available, which display an overall mild phenotype consisting of a mitochondrial dysfunction together with changes in dopamine metabolism and oxidative stress. However, up till now these models fail to reproduce the main hallmarks of Parkinson's disease: the dopaminergic cell loss in the substantia nigra and the presence of cytoplasmic inclusions, named Lewy bodies, in the remaining dopaminergic neurons. We here review the most important knockout and knockdown rodent models generated so far for these two recessive Parkinson's disease-causing genes. We critically feature their main characteristics and their impact on the research field, and propose some future directions for the study and modelling of the loss of function of parkin and PINK1 in rodents.

  5. Genetic Analysis of PARK2 and PINK1 Genes in Brazilian Patients with Early-Onset Parkinson's Disease

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    Karla Cristina Vasconcelos Moura

    2013-01-01

    Full Text Available Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5–10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9% than PINK1 missense variants (0%, corroborating other studies worldwide.

  6. Drosophila ref(2)P is required for the parkin-mediated suppression of mitochondrial dysfunction in pink1 mutants.

    Science.gov (United States)

    de Castro, I P; Costa, A C; Celardo, I; Tufi, R; Dinsdale, D; Loh, S H Y; Martins, L M

    2013-10-24

    Autophagy is a critical regulator of organellar homeostasis, particularly of mitochondria. Upon the loss of membrane potential, dysfunctional mitochondria are selectively removed by autophagy through recruitment of the E3 ligase Parkin by the PTEN-induced kinase 1 (PINK1) and subsequent ubiquitination of mitochondrial membrane proteins. Mammalian sequestrome-1 (p62/SQSTM1) is an autophagy adaptor, which has been proposed to shuttle ubiquitinated cargo for autophagic degradation downstream of Parkin. Here, we show that loss of ref(2)P, the Drosophila orthologue of mammalian P62, results in abnormalities, including mitochondrial defects and an accumulation of mitochondrial DNA with heteroplasmic mutations, correlated with locomotor defects. Furthermore, we show that expression of Ref(2)P is able to ameliorate the defects caused by loss of Pink1 and that this depends on the presence of functional Parkin. Finally, we show that both the PB1 and UBA domains of Ref(2)P are crucial for mitochondrial clustering. We conclude that Ref(2)P is a crucial downstream effector of a pathway involving Pink1 and Parkin and is responsible for the maintenance of a viable pool of cellular mitochondria by promoting their aggregation and autophagic clearance.

  7. Regulation of PINK1 by NR2B-containing NMDA receptors in ischemic neuronal injury.

    Science.gov (United States)

    Shan, Yuexin; Liu, Baosong; Li, Lijun; Chang, Ning; Li, Lei; Wang, Hanbin; Wang, Dianshi; Feng, Hua; Cheung, Carol; Liao, Mingxia; Cui, Tianyuan; Sugita, Shuzo; Wan, Qi

    2009-12-01

    Dysfunction of PTEN-induced kinase-1 (PINK1) is implicated in neurodegeneration. We report here that oxygen-glucose deprivation (OGD), an in vitro insult mimicking ischemic neuron injury, resulted in a significant reduction of PINK1 protein expression in cultured cortical neurons. The decrease of PINK1 expression was blocked by the antagonists of NMDA receptors. We revealed that the overactivation of NR2B-containing NMDA receptors (NR2BRs) was responsible for the OGD-induced PINK1 reduction. The overactivated NR2BRs also inhibited the phosphorylation, but not the protein expression, of the cell survival-promoting kinase Akt after OGD insult, indicating that OGD-induced reduction of PINK1 protein is specific in the injury paradigm. We further showed that enhancing the protein expression of PINK1 antagonized OGD-induced reduction of Akt phosphorylation, suggesting that Akt may be a downstream target of PINK1 in ischemic neuron injury. Importantly, we provided evidence that both NR2BR antagonist and PINK1 over-expression protected against OGD-induced neuronal death. These results suggest that the overactivation of NR2BRs may contribute to ischemic neuron death through suppressing PINK1-dependent survival signaling. Thus, selectively antagonizing NR2BR signal pathway-induced neurotoxicity may be a potential neuroprotection strategy.

  8. PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons.

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    Alison Wood-Kaczmar

    Full Text Available Parkinson's disease (PD is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.

  9. The loss of PGAM5 suppresses the mitochondrial degeneration caused by inactivation of PINK1 in Drosophila.

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    Yuzuru Imai

    Full Text Available PTEN-induced kinase 1 (PINK1, which is required for mitochondrial homeostasis, is a gene product responsible for early-onset Parkinson's disease (PD. Another early onset PD gene product, Parkin, has been suggested to function downstream of the PINK1 signalling pathway based on genetic studies in Drosophila. PINK1 is a serine/threonine kinase with a predicted mitochondrial target sequence and a probable transmembrane domain at the N-terminus, while Parkin is a RING-finger protein with ubiquitin-ligase (E3 activity. However, how PINK1 and Parkin regulate mitochondrial activity is largely unknown. To explore the molecular mechanism underlying the interaction between PINK1 and Parkin, we biochemically purified PINK1-binding proteins from human cultured cells and screened the genes encoding these binding proteins using Drosophila PINK1 (dPINK1 models to isolate a molecule(s involved in the PINK1 pathology. Here we report that a PINK1-binding mitochondrial protein, PGAM5, modulates the PINK1 pathway. Loss of Drosophila PGAM5 (dPGAM5 can suppress the muscle degeneration, motor defects, and shorter lifespan that result from dPINK1 inactivation and that can be attributed to mitochondrial degeneration. However, dPGAM5 inactivation fails to modulate the phenotypes of parkin mutant flies. Conversely, ectopic expression of dPGAM5 exacerbated the dPINK1 and Drosophila parkin (dParkin phenotypes. These results suggest that PGAM5 negatively regulates the PINK1 pathway related to maintenance of the mitochondria and, furthermore, that PGAM5 acts between PINK1 and Parkin, or functions independently of Parkin downstream of PINK1.

  10. PINK1 positively regulates IL-1β-mediated signaling through Tollip and IRAK1 modulation

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    Lee Hyun Jung

    2012-12-01

    Full Text Available Abstract Background Parkinson disease (PD is characterized by a slow, progressive degeneration of dopaminergic neurons in the substantianigra. The cause of neuronal loss in PD is not well understood, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1, have been linked to early-onset autosomal recessive forms of familial PD. Neuroinflammation greatly contributes to PD neuronal degeneration and pathogenesis. IL-1 is one of the principal cytokines that regulates various immune and inflammatory responses via the activation of the transcription factors NF-κB and activating protein-1. Despite the close relationship between PD and neuroinflammation, the functional roles of PD-linked genes during inflammatory processes remain poorly understood. Methods To explore the functional roles of PINK1 in response to IL-1β stimulation, HEK293 cells, mouse embryonic fibroblasts derived from PINK1-null (PINK1−/− and control (PINK1+/+ mice, and 293 IL-1RI cells stably expressing type 1 IL-1 receptor were used. Immunoprecipitation and western blot analysis were performed to detect protein–protein interaction and protein ubiquitination. To confirm the effect of PINK1 on NF-κB activation, NF-κB-dependent firefly luciferase reporter assay was conducted. Results PINK1 specifically binds two components of the IL-1-mediated signaling cascade, Toll-interacting protein (Tollip and IL-1 receptor-associated kinase 1 (IRAK1. The association of PINK1 with Tollip, a negative regulator of IL-1β signaling, increases upon IL-1β stimulation, which then facilitates the dissociation of Tollip from IRAK1 as well as the assembly of the IRAK1–TNF receptor-associated factor 6 (TRAF6 complex. PINK1 also enhances Lys63-linked polyubiquitination of IRAK1, an essential modification of recruitment of NF-κB essential modulator and subsequent IκB kinase activation, and increases formation of the intermediate signalosome including IRAK1, TRAF6, and

  11. "PINK1"-Linked Parkinsonism Is Associated with Lewy Body Pathology

    Science.gov (United States)

    Samaranch, Lluis; Lorenzo-Betancor, Oswaldo; Arbelo, Jose M.; Ferrer, Isidre; Lorenzo, Elena; Irigoyen, Jaione; Pastor, Maria A.; Marrero, Carmen; Isla, Concepcion; Herrera-Henriquez, Joanna; Pastor, Pau

    2010-01-01

    Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed…

  12. "PINK1"-Linked Parkinsonism Is Associated with Lewy Body Pathology

    Science.gov (United States)

    Samaranch, Lluis; Lorenzo-Betancor, Oswaldo; Arbelo, Jose M.; Ferrer, Isidre; Lorenzo, Elena; Irigoyen, Jaione; Pastor, Maria A.; Marrero, Carmen; Isla, Concepcion; Herrera-Henriquez, Joanna; Pastor, Pau

    2010-01-01

    Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed…

  13. Expression of PINK1 in the brain, eye and ear of mouse during embryonic development.

    Science.gov (United States)

    d'Amora, Marta; Angelini, Cristiano; Marcoli, Manuela; Cervetto, Chiara; Kitada, Tohru; Vallarino, Mauro

    2011-03-01

    PINK1 is a 581 amino acid protein with a serine/threonine kinase domain and an N-terminal mitochondrial targeting motif. The enzyme is expressed in the brain as well as in several tissues such as heart, skeletal muscle, liver, kidney, pancreas and testis. In the present study, we have investigated by Western blot analysis and immunohistochemistry the presence and distribution of PINK1 in the brain, eye and inner ear of mouse during embryonic development. In the brain we detected two PINK1 molecular isoforms of 55 kDa and 66 kDa. Immunoreactive perikarya first appeared at stage E15 in the diencephalon within the thalamus, the hypothalamus, the periventricular layers of the third ventricle and in the rhombencephalon at level of the pons. Subsequently, new PINK1-positive neurons were found in the midbrain within the floor and the periventricular layers of the ventral wall of the mesencephalic vesicle (stage E17) as well as in the neopallial cortex, the tegmentum of the midbrain and the periventricular region of the caudal part of the rhombencephalon (stage E19). At P0, PINK1-immunoreactive cells appeared in the striatum, the mantle layer and caudal part of the medulla oblongata and the cerebellum. The spatio-temporal expression of PINK1 and its heterogeneous distribution suggest that the enzyme might be involved in neuroregulatory processes during embryogenesis. In the eye, PINK1-immunoreactivity was found in the lens and in the cornea, whereas in the inner ear the enzyme was expressed in the ependymal and subependymal cells of the saccule and in the semicircular canals indicating that PINK1 plays a role in the development of these sensory organs. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery.

    Science.gov (United States)

    Yang, Yufeng; Ouyang, Yingshi; Yang, Lichuan; Beal, M Flint; McQuibban, Angus; Vogel, Hannes; Lu, Bingwei

    2008-05-13

    Mitochondria form dynamic tubular networks that undergo frequent morphological changes through fission and fusion, the imbalance of which can affect cell survival in general and impact synaptic transmission and plasticity in neurons in particular. Some core components of the mitochondrial fission/fusion machinery, including the dynamin-like GTPases Drp1, Mitofusin, Opa1, and the Drp1-interacting protein Fis1, have been identified. How the fission and fusion processes are regulated under normal conditions and the extent to which defects in mitochondrial fission/fusion are involved in various disease conditions are poorly understood. Mitochondrial malfunction tends to cause diseases with brain and skeletal muscle manifestations and has been implicated in neurodegenerative diseases such as Parkinson's disease (PD). Whether abnormal mitochondrial fission or fusion plays a role in PD pathogenesis has not been shown. Here, we show that Pink1, a mitochondria-targeted Ser/Thr kinase linked to familial PD, genetically interacts with the mitochondrial fission/fusion machinery and modulates mitochondrial dynamics. Genetic manipulations that promote mitochondrial fission suppress Drosophila Pink1 mutant phenotypes in indirect flight muscle and dopamine neurons, whereas decreased fission has opposite effects. In Drosophila and mammalian cells, overexpression of Pink1 promotes mitochondrial fission, whereas inhibition of Pink1 leads to excessive fusion. Our genetic interaction results suggest that Fis1 may act in-between Pink1 and Drp1 in controlling mitochondrial fission. These results reveal a cell biological role for Pink1 and establish mitochondrial fission/fusion as a paradigm for PD research. Compounds that modulate mitochondrial fission/fusion could have therapeutic value in PD intervention.

  15. PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila.

    Directory of Open Access Journals (Sweden)

    Kahori Shiba-Fukushima

    2014-06-01

    Full Text Available Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. We have reported that Parkin is phosphorylated at Ser65 within the ubiquitin-like domain by PINK1 in mammalian cultured cells. However, it remains unclear whether Parkin phosphorylation is involved in mitochondrial maintenance and activity of dopaminergic neurons in vivo. Here, we examined the effects of Parkin phosphorylation in Drosophila, in which the phosphorylation residue is conserved at Ser94. Morphological changes of mitochondria caused by the ectopic expression of wild-type Parkin in muscle tissue and brain dopaminergic neurons disappeared in the absence of PINK1. In contrast, phosphomimetic Parkin accelerated mitochondrial fragmentation or aggregation and the degradation of mitochondrial proteins regardless of PINK1 activity, suggesting that the phosphorylation of Parkin boosts its ubiquitin-ligase activity. A non-phosphorylated form of Parkin fully rescued the muscular mitochondrial degeneration due to the loss of PINK1 activity, whereas the introduction of the non-phosphorylated Parkin mutant in Parkin-null flies led to the emergence of abnormally fused mitochondria in the muscle tissue. Manipulating the Parkin phosphorylation status affected spontaneous dopamine release in the nerve terminals of dopaminergic neurons, the survivability of dopaminergic neurons and flight activity. Our data reveal that Parkin phosphorylation regulates not only mitochondrial function but also the neuronal activity of dopaminergic neurons in vivo, suggesting that the appropriate regulation of Parkin phosphorylation is important for muscular and dopaminergic functions.

  16. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin

    Science.gov (United States)

    Ashrafi, Ghazaleh; Schlehe, Julia S.; LaVoie, Matthew J.

    2014-01-01

    To minimize oxidative damage to the cell, malfunctioning mitochondria need to be removed by mitophagy. In neuronal axons, mitochondrial damage may occur in distal regions, far from the soma where most lysosomal degradation is thought to occur. In this paper, we report that PINK1 and Parkin, two Parkinson’s disease–associated proteins, mediate local mitophagy of dysfunctional mitochondria in neuronal axons. To reduce cytotoxicity and mimic physiological levels of mitochondrial damage, we selectively damaged a subset of mitochondria in hippocampal axons. Parkin was rapidly recruited to damaged mitochondria in axons followed by formation of LC3-positive autophagosomes and LAMP1-positive lysosomes. In PINK1−/− axons, damaged mitochondria did not accumulate Parkin and failed to be engulfed in autophagosomes. Similarly, initiation of mitophagy was blocked in Parkin−/− axons. Our findings demonstrate that the PINK1–Parkin-mediated pathway is required for local mitophagy in distal axons in response to focal damage. Local mitophagy likely provides rapid neuroprotection against oxidative stress without a requirement for retrograde transport to the soma. PMID:25154397

  17. 帕金森病相关蛋白Parkin与PINK1的相互作用研究%Direct Interaction Between Two Parkinson-related Protein Parkin and PINK1

    Institute of Scientific and Technical Information of China (English)

    王雪晶; 郭纪锋; 江泓; 沈璐; 唐北沙

    2010-01-01

    帕金森病(Parkinson's disease,PD)是常见的神经系统变性疾病.分子遗传学研究发现,突变的Parkin蛋白及PINK1蛋白均参与了帕金森病的致病过程,但二者之间是否存在相互作用以及是否能够相互调节仍不十分清楚.为明确生理状态下Parkin蛋白与PINK1蛋白之间的相瓦作用,首先运用蛋白体外结合实验(GST pull-down)技术及免疫共沉淀技术证实了Parkin与PINK1在体外及体内均可相互结合.进一步构建PINK1的不同截短型,运用GST pull-down技术验证了PINK1与Parkin相互结合的区段为PINK1的蛋白激酶结构域.免疫细胞化学实验也证实Parkin与PINK1蛋白在细胞中存在共定位.进一步运用免疫共沉淀技术证实Parkin可减少PINK1通过泛素蛋白酶体系统(ubiquitin proteasome system,UPS)的降解,从而稳定PINK1.PINK1可增加Parkin通过UPS的降解,从而减少Parkin的水平,降低其稳定性.这些结果提示,帕金森病相关蛋白Parkin与PINK1能够直接结合,二者通过泛素蛋白酶体降解系统相互调节,可能协同作用参与了帕金森病的致病过程.

  18. Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells

    Science.gov (United States)

    Wei, Limin; Wang, Jianfeng; Chen, Aijie; Liu, Jia; Feng, Xiaoli; Shao, Longquan

    2017-01-01

    With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1−/− BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity. PMID:28331313

  19. 帕金森病患者PINK 1基因的突变研究

    Institute of Scientific and Technical Information of China (English)

    袁静; 刘艺鸣; 肖志英; 于博

    2010-01-01

    目的 观察我国帕金森病(Parkinson's disease,PD)患者中是否存在PINK 1的基因突变,并结合临床症状,分析、探讨基因突变或缺失对帕金森病患者临床症状的影响.同时,通过基因学的研究来探讨PINK 1基因突变与早发型PD及晚发型PD的关系.方法 应用聚合酶链反应(PCR)及DNA测序技术进行PINK 1基因的突变分析.结果 未发现外显子3、4缺失,外显子2缺失3例.DNA测序发现1例家族性PD患者PINK 1基因外显子2中G153A杂合子突变.2例散发PD患者PINK 1基因外显子3中内含子突变.PINK 1基因在早发型和晚发型PD患者之间无显著的统计学意义(P>0.05).结论 存在PINK 1基因突变的PD患者初发症状多以震颤为主,症状波动、抑郁、便秘、睡眠障碍症状较严重,其中杂合子突变对PD有何明确意义尚需进一步的研究.且PINK 1基因缺失突变在早发型与晚发型PD中可能无区别.

  20. Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease.

    Science.gov (United States)

    Venderova, Katerina; Kabbach, Ghassan; Abdel-Messih, Elizabeth; Zhang, Yi; Parks, Robin J; Imai, Yuzuru; Gehrke, Stephan; Ngsee, Johnny; Lavoie, Matthew J; Slack, Ruth S; Rao, Yong; Zhang, Zhuohua; Lu, Bingwei; Haque, M Emdadul; Park, David S

    2009-11-15

    Mutations in the LRRK2 gene are the most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions are unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human LRRK2 (mutations in kinase, COR or LRR domains, resp.). Ectopic expression of WT or mutant LRRK2 in dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes in locomotor activity. Overall, the ubiquitous expression of LRRK2 increased lifespan and fertility of the flies. However, these flies were more sensitive to rotenone. LRRK2 expression in the eye exacerbated retinal degeneration. Importantly, in double transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.

  1. Common variants of the PINK1 and PARL genes do not confer genetic susceptibility to schizophrenia in Han Chinese.

    Science.gov (United States)

    Li, Xiao; Zhang, Wen; Zhang, Chen; Yi, Zhenghui; Zhang, Deng-Feng; Gong, Wei; Tang, Jinsong; Wang, Dong; Lu, Weihong; Chen, Xiaogang; Fang, Yiru; Yao, Yong-Gang

    2015-04-01

    Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia.

  2. PINK1-Parkin-Mediated Mitophagy Protects Mitochondrial Integrity and Prevents Metabolic Stress-Induced Endothelial Injury.

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    Weiwei Wu

    Full Text Available Mitochondrial injury and dysfunction, a significant feature in metabolic syndrome, triggers endothelial cell dysfunction and cell death. Increasing evidence suggests that mitophagy, a process of autophagic turnover of damaged mitochondria, maintains mitochondrial integrity. PINK1 (phosphatase and tensin homolog (PTEN-induced putative kinase 1 and Parkin signaling is a key pathway in mitophagy control. In this study, we examined whether this pathway could protect mitochondria under metabolic stress. We found that palmitic acid (PA induced significant mitophagy and activated PINK1 and Parkin in endothelial cells. Knocking down PINK1 or Parkin reduced mitophagy, leading to impaired clearance of damaged mitochondria and intracellular accumulation of mitochondrial fragments. Furthermore, PINK1 and Parkin prevented PA-induced mitochondrial dysfunction, ROS production and apoptosis. Finally, we show that PINK1 and Parkin were up-regulated in vascular wall of obese mice and diabetic mice. Our study demonstrates that PINK1-Parkin pathway is activated in response to metabolic stress. Through induction of mitophagy, this pathway protects mitochondrial integrity and prevents metabolic stress-induced endothelial injury.

  3. Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China

    Science.gov (United States)

    Wang, Dong; Zhang, Deng-Feng; Feng, Jia-Qi; Li, Guo-Dong; Li, Xiao-An; Yu, Xiu-Feng; Long, Heng; Li, Yu-Ye; Yao, Yong-Gang

    2016-01-01

    Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy. PMID:27876828

  4. Genomic variants at the PINK1 locus are associated with transcript abundance and plasma nonesterified fatty acid concentrations in European whites

    DEFF Research Database (Denmark)

    Franks, P.W.; Scheele, C.; Loos, R.J.

    2008-01-01

    The purpose of this study was to characterize associations between PINK1 genotypes, PINK1 transcript levels, and metabolic phenotypes in healthy adults and those with type 2 diabetes (T2D). We measured PINK1 skeletal muscle transcript levels and 8 independent PINK1 single nucleotide polymorphisms...... (SNPs) in a cohort of 208 Danish whites and in a cohort of 1701 British whites (SNPs and metabolic phenotypes only). Furthermore, we assessed the effects of PINK1 transcript ablation in primary adipocytes using RNA interference (RNAi). Six PINK1 SNPs were associated with PINK1 transcript levels (P....04 to PPINK1 transcript levels and T2D risk (interaction P=0.005); transcript levels were inversely related with T2D in obese (n=105) [odds ratio (OR) per sd increase in expression levels=0.44; 95% confidence interval (CI): 0.23, 0.84; P=0...

  5. PINK1/Parkin-Dependent Mitochondrial Surveillance: From Pleiotropy to Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Olga Corti

    2017-05-01

    Full Text Available Parkinson's disease (PD is one of the most frequent neurodegenerative disease caused by the preferential, progressive degeneration of the dopaminergic (DA neurons of the substantia nigra (SN pars compacta. PD is characterized by a multifaceted pathological process involving protein misfolding, mitochondrial dysfunction, neuroinflammation and metabolism deregulation. The molecular mechanisms governing the complex interplay between the different facets of this process are still unknown. PARK2/Parkin and PARK6/PINK1, two genes responsible for familial forms of PD, act as a ubiquitous core signaling pathway, coupling mitochondrial stress to mitochondrial surveillance, by regulating mitochondrial dynamics, the removal of damaged mitochondrial components by mitochondria-derived vesicles, mitophagy, and mitochondrial biogenesis. Over the last decade, PINK1/Parkin-dependent mitochondrial quality control emerged as a pleiotropic regulatory pathway. Loss of its function impinges on a number of physiological processes suspected to contribute to PD pathogenesis. Its role in the regulation of innate immunity and inflammatory processes stands out, providing compelling support to the contribution of non-cell-autonomous immune mechanisms in PD. In this review, we illustrate the central role of this multifunctional pathway at the crossroads between mitochondrial stress, neuroinflammation and metabolism. We discuss how its dysfunction may contribute to PD pathogenesis and pinpoint major unresolved questions in the field.

  6. Downregulation of Pink1 influences mitochondrial fusion–fission machinery and sensitizes to neurotoxins in dopaminergic cells

    Science.gov (United States)

    Rojas-Charry, Liliana; Cookson, Mark R.; Niño, Andrea; Arboleda, Humberto; Arboleda, Gonzalo

    2016-01-01

    It is now well established that mitochondria are organelles that, far from being static, are subject to a constant process of change. This process, which has been called mitochondrial dynamics, includes processes of both fusion and fission. Loss of Pink1 (PTEN-induced putative kinase 1) function is associated with early onset recessive Parkinson’s disease and it has been proposed that mitochondrial dynamics might be affected by loss of the mitochondrial kinase. Here, we report the effects of silencing Pink1 on mitochondrial fusion and fission events in dopaminergic neuron cell lines. Cells lacking Pink1 were more sensitive to cell death induced by C2-Ceramide, which inhibits proliferation and induces apoptosis. In the same cell lines, mitochondrial morphology was fragmented and this was enhanced by application of forskolin, which stimulates the cAMP pathway that phosphorylates Drp1 and thereby inactivates it. Cells lacking Pink1 had lower Drp1 and Mfn2 expression. Based on these data, we propose that Pink1 may exert a neuroprotective role in part by limiting mitochondrial fission. PMID:24792327

  7. E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia

    Directory of Open Access Journals (Sweden)

    Bill B. Chen

    2014-04-01

    Full Text Available Acute lung injury (ALI is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1. Here, we show that S. aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN-induced putative kinase 1 (PINK1, which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S. aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S. aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme.

  8. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.

    Science.gov (United States)

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A; Hernandez, Dena G; Heutink, Peter; Gibbs, J Raphael; Hardy, John; Wood, Nicholas W; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis

    2016-03-03

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy

    Science.gov (United States)

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A.; Hernandez, Dena G.; Heutink, Peter; Gibbs, J. Raphael; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Viallet, François; Brice, Alexis; Lesage, Suzanne; Majounie, Elisa; Tison, François; Vidailhet, Marie; Corvol, Jean Christophe; Nalls, Michael A.; Hernandez, Dena G.; Gibbs, J. Raphael; Dürr, Alexandra; Arepalli, Sampath; Barker, Roger A.; Ben-Shlomo, Yoav; Berg, Daniela; Bettella, Francesco; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bastiaan R.; Bochdanovits, Zoltan; Bonin, Michael; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Dong, Jing; Durif, Frank; Edkins, Sarah; Escott-Price, Valentina; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michèle; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Kilarski, Laura L.; Jansen, Iris E.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Lubbe, Steven; Lungu, Codrin; Martinez, María; Mätzler, Walter; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morrison, Karen E.; Mudanohwo, Ese; O’Sullivan, Sean S.; Owen, Michael J.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Simón-Sánchez, Javier; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Schulte, Claudia; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Shulman, Joshua; Sidransky, Ellen; Spencer, Chris C.A.; Stefánsson, Hreinn; Stefánsson, Kári; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wurster, Isabel; Williams, Nigel; Morris, Huw R.; Heutink, Peter; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Singleton, Andrew B.; Brice, Alexis

    2016-01-01

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

  10. PKA Phosphorylation of NCLX Reverses Mitochondrial Calcium Overload and Depolarization, Promoting Survival of PINK1-Deficient Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Marko Kostic

    2015-10-01

    Full Text Available Mitochondrial Ca2+ overload is a critical, preceding event in neuronal damage encountered during neurodegenerative and ischemic insults. We found that loss of PTEN-induced putative kinase 1 (PINK1 function, implicated in Parkinson disease, inhibits the mitochondrial Na+/Ca2+ exchanger (NCLX, leading to impaired mitochondrial Ca2+ extrusion. NCLX activity was, however, fully rescued by activation of the protein kinase A (PKA pathway. We further show that PKA rescues NCLX activity by phosphorylating serine 258, a putative regulatory NCLX site. Remarkably, a constitutively active phosphomimetic mutant of NCLX (NCLXS258D prevents mitochondrial Ca2+ overload and mitochondrial depolarization in PINK1 knockout neurons, thereby enhancing neuronal survival. Our results identify an mitochondrial Ca2+ transport regulatory pathway that protects against mitochondrial Ca2+ overload. Because mitochondrial Ca2+ dyshomeostasis is a prominent feature of multiple disorders, the link between NCLX and PKA may offer a therapeutic target.

  11. Atp13a2 expression in the periaqueductal gray is decreased in the Pink1 -/- rat model of Parkinson disease.

    Science.gov (United States)

    Kelm-Nelson, Cynthia A; Stevenson, Sharon A; Ciucci, Michelle R

    2016-05-16

    Vocal communication deficits are common in Parkinson disease (PD). Widespread alpha-synuclein pathology is a common link between familial and sporadic PD, and recent genetic rat models based on familial genetic links increase the opportunity to explore vocalization deficits and their associated neuropathologies. Specifically, the Pink1 knockout (-/-) rat presents with early, progressive motor deficits, including significant vocal deficits, at 8 months of age. Moreover, this rat model exhibits alpha-synuclein pathology compared to age-matched non-affected wildtype (WT) controls. Aggregations are specifically dense within the periaqueductal gray (PAG), a brainstem region involved in the coordination of emotional and volitional control of vocalizations. Here, we investigated changes in gene expression within the PAG at 8 months of age in Pink1 -/- rats compared to WT. Our data demonstrate that Pink1 -/- rat mRNA expression levels of alpha-synuclein are comparable to WT. However, Pink1 -/- rats show significantly decreased levels of Atp13a2, a transmembrane lysosomal P5-type ATPase suggesting a potential mechanism for the observed abnormal aggregation. We found no difference in the expression of glucocerebrosidase (Gba) or the CASP8 and FADD-like apoptosis regulator (Cflar). Further, we show that mRNA expression levels of dopaminergic markers including Th, D1 and D2 receptor as well as GABA signaling markers including Gaba-A and glutamate decarboxylase 2 (Gad2) do not differ between genotypes. However, we found that glutamate decarboxylase 1 (Gad1) is significantly reduced in this PD model suggesting possible disruption of neurotransmission within the PAG. These results are the first to suggest the hypothesis that alpha-synuclein aggregation in this model is not a result of increased transcription, but rather a deficit in the breakdown and clearance, and that the observed vocal deficits may be related to impaired neural transmission. Altogether, these findings are

  12. Haplotype identity between individuals who share a CFTR mutation allele ''identical by descent'' : Demonstration of the usefulness of the haplotype-sharing concept for gene mapping in real populations

    NARCIS (Netherlands)

    deVries, HG; vanderMeulen, MA; Rozen, R; Halley, DJJ; Scheffer, H; tenKate, LP; Buys, CHCM; teMeerman, GJ

    1996-01-01

    Cystic fibrosis (CF) patients with the A455E mutation, in both the French Canadian and the Dutch population, share a common haplotype over distances of up to 25 cM. French Canadian patients with the 621+1G-->T mutation share a common haplotype of more than 14 cM. In contrast, haplotypes containing t

  13. Haplotype identity between individuals who share a CFTR mutation allele 'identical by descent': Demonstration of the usefulness of the haplotype-sharing concept for gene mapping in real populations

    NARCIS (Netherlands)

    H.G. de Vries (Hendrik); M.A. van der Meulen (Martin); R. Rozen (Rima); D.J.J. Halley (Dicky); H. Scheffer (Hans); L.P. ten Kate; C.H.C.M. Buys; G.J. Te Meerman (Gerard)

    1996-01-01

    markdownabstractAbstract Cystic fibrosis (CF) patients with the A455E mutation, in both the French Canadian and the Dutch population, share a common haplotype over distances of up to 25 cM. French Canadian patients with the 621+1G→T mutation share a common haplotype of more than 14 cM. In contras

  14. Mucuna pruriens (Velvet bean rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Simone Poddighe

    Full Text Available The fruit fly Drosophila melanogaster (Dm mutant for PTEN-induced putative kinase 1 (PINK1B9 gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD. Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe, a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3-6 (I, 10-15 (II and 20-25 (III days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1% ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP and tyrosine hydroxylase (TH expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment.

  15. A novel PGC-1α isoform in brain localizes to mitochondria and associates with PINK1 and VDAC

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Joungil, E-mail: jochoi@som.umaryland.edu [Department of Neurology, University of Maryland, Baltimore, MD 21201 (United States); Veterans Affairs Medical Center, Baltimore, MD 21201 (United States); Batchu, Vera Venkatanaresh Kumar [Department of Neurology, University of Maryland, Baltimore, MD 21201 (United States); Veterans Affairs Medical Center, Baltimore, MD 21201 (United States); Schubert, Manfred [National Institute of Neurological Disorders and Stroke, Baltimore, MD 21201 (United States); Castellani, Rudolph J. [Department of Pathology, University of Maryland, Baltimore, MD 21201 (United States); Russell, James W. [Department of Neurology, University of Maryland, Baltimore, MD 21201 (United States); Veterans Affairs Medical Center, Baltimore, MD 21201 (United States)

    2013-06-14

    Highlights: •Novel 35 kDa PGC-1α localizes to mitochondrial inner membrane and matrix in brain. •Mitochondrial localization of 35 kDa PGC-1α depends on VDAC protein. •Mitochondrial localization of 35 kDa PGC-1α depends on membrane potential. •The 35 kDa PGC-1α associates and colocalizes with PINK in brain mitochondria. -- Abstract: Peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) and PTEN-induced putative kinase 1 (PINK1) are powerful regulators of mitochondrial function. Here, we report that a previously unrecognized, novel 35 kDa PGC-1α isoform localizes to the mitochondrial inner membrane and matrix in brain as determined by protease protection and carbonate extraction assays, as well as by immunoelectron microscopy. Immunoelectron microscopy and import experiments in vitro revealed that 35 kDa PGC-1α colocalizes and interacts with the voltage-dependent anion channel (VDAC), and that its import depends on VDAC. Valinomycin treatment which depolarizes the membrane potential, abolished mitochondrial localization of the 35 kDa PGC-1α. Using blue native-PAGE, co-immunoprecipitation, and immunoelectron microscopy analyses, we found that the 35 kDa PGC-1α binds and colocalizes with PINK1 in brain mitochondria. This is the first report regarding mitochondrial localization of a novel 35 kDa PGC-1α isoform and its association with PINK1, suggesting possible regulatory roles for mitochondrial function in the brain.

  16. Parkin,PINK1,DJ-1 and mitochondria dysfunction with Parkinson's disease%Parkin、PINK1、DJ-1和线粒体功能障碍与帕金森病

    Institute of Scientific and Technical Information of China (English)

    杨辉; 左伋; 刘雯

    2010-01-01

    帕金森病(Parkinson's disese,PD)是一种常见的神经退行性疾病,但到目前为止发病机制尚不明确,环境和遗传等因素与其发病有密切关系.研究表明,蛋白质异常积聚(泛素/蛋白酶体途径)和线粒体氧化损伤(线粒体途径),可能是导致PD患者发病的关键分子机制.Parkin、PINK1和DJ-1等基因突变与常染色体隐性的家族性PD有关,这些相关基因编码的蛋白对于维持线粒体形态和功能起着重要的作用.本文将主要从Parkin、PINK1、DJ-1和线粒体功能障碍与帕金森病的关系进行综述.

  17. PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation

    Science.gov (United States)

    Choi, Insup; Woo, Joo Hong; Jou, Ilo

    2016-01-01

    PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development. PMID:26924929

  18. Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular testing implications.

    Science.gov (United States)

    Monroy-Jaramillo, Nancy; Guerrero-Camacho, Jorge Luis; Rodríguez-Violante, Mayela; Boll-Woehrlen, Marie-Catherine; Yescas-Gómez, Petra; Alonso-Vilatela, María Elisa; López-López, Marisol

    2014-04-01

    Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive early-onset Parkinson's disease. Here, we report the prevalence of sequence and structural mutations in these three main recessive genes in Mexican Mestizo patients. The complete sequences of these three genes were analyzed by homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined by multiplex ligation-dependent probe amplification and real-time PCR in 127 patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All individuals had been previously screened for the three most common LRRK2 mutations. The presence of two mutations in compound heterozygous or homozygous genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were observed. Novel mutations were identified in PARK2 and PINK1 genes, including PINK1 duplication for the first time. Exon dosage deletions were the most frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the novel heterozygous and homozygous point mutations in PINK1 observed in familial and sporadic cases from various states of Mexico support the concept that single heterozygous mutations in recessive Parkinson's disease genes play a pathogenic role. These data have important implications for genetic counseling of Mexican Mestizo patients with early-onset Parkinson's disease. The presence of digenic inheritance underscores the importance of studying several genes in this disease. A step-ordered strategy for molecular diagnosis is proposed.

  19. Unaltered striatal dopamine release levels in young Parkin knockout, Pink1 knockout, DJ-1 knockout and LRRK2 R1441G transgenic mice.

    Directory of Open Access Journals (Sweden)

    Gonzalo Sanchez

    Full Text Available Parkinson's disease (PD is one of the most prevalent neurodegenerative brain diseases; it is accompanied by extensive loss of dopamine (DA neurons of the substantia nigra that project to the putamen, leading to impaired motor functions. Several genes have been associated with hereditary forms of the disease and transgenic mice have been developed by a number of groups to produce animal models of PD and to explore the basic functions of these genes. Surprisingly, most of the various mouse lines generated such as Parkin KO, Pink1 KO, DJ-1 KO and LRRK2 transgenic have been reported to lack degeneration of nigral DA neuron, one of the hallmarks of PD. However, modest impairments of motor behavior have been reported, suggesting the possibility that the models recapitulate at least some of the early stages of PD, including early dysfunction of DA axon terminals. To further evaluate this possibility, here we provide for the first time a systematic comparison of DA release in four different mouse lines, examined at a young age range, prior to potential age-dependent compensations. Using fast scan cyclic voltammetry in striatal sections prepared from young, 6-8 weeks old mice, we examined sub-second DA overflow evoked by single pulses and action potential trains. Unexpectedly, none of the models displayed any dysfunction of DA overflow or reuptake. These results, compatible with the lack of DA neuron loss in these models, suggest that molecular dysfunctions caused by the absence or mutation of these individual genes are not sufficient to perturb the function and survival of mouse DA neurons.

  20. Development of a Tool to Guide Parents Carrying a BRCA1/2 Mutation Share Genetic Results with Underage Children.

    Science.gov (United States)

    Santerre-Theil, Ariane; Bouchard, Karine; St-Pierre, Dominique; Drolet, Anne-Marie; Chiquette, Jocelyne; Dorval, Michel

    2016-11-02

    Although most parents carrying a BRCA1/2 genetic mutation share their test result with their underage children, they report needing support to decide if, when, and how to share risk information and what reactions to expect from their children. We developed a tool to guide parents carrying a BRCA1/2 mutation share their genetic result with underage children. Here, we report on the development of this tool using a qualitative methodology. A tool prototype was developed based on the International Patient Decision Aids Standards Collaboration framework. Content was assessed using feedback from focus groups, individual interviews, and a 12-item reading grid. Participants were nine BRCA1/2 mutation carriers with underage children and three cancer genetics health professionals. Thematic content analysis was conducted on interview transcripts. The tool was developed using an iterative process until saturation of data. An independent advisory committee was involved in all steps of tool development until reaching consensus. Rather than a decision aid per se (to communicate or not), the parents wanted a more comprehensive tool to help them communicate genetic test result to their children. To meet parents' needs, a communication guidance booklet was developed, setting out the pros and cons of communication, steps to prepare sharing the test result, communication tips, and parents' testimonies. This communication tool responds to a significant unmet need faced by parents carrying a genetic predisposition to cancer. Future studies are needed to assess how the information from the parent's genetic test result impacts the child's development, health behaviors, and relationship with the parent.

  1. Randomized trial of a shared decision-making intervention consisting of trade-offs and individualized treatment information for BRCA1/2 mutation carriers

    NARCIS (Netherlands)

    van Roosmalen, MS; Stalmeier, PFM; Verhoef, LCG; Hoekstra-Weebers, JEHM; Oosterwijk, JC; Hoogerbrugge, N; Moog, U; van Daal, WAJ

    2004-01-01

    Purpose To evaluate a shared decision-making intervention (SDMI) for BRCA1/2 mutation carriers who have to make a choice between screening and prophylactic surgery for breasts and/or ovaries. Patients and Methods The SDMI consisted of two value assessment sessions, using the time trade-off method,

  2. Molecular evolution of the human immunoglobulin E response: high incidence of shared mutations and clonal relatedness among epsilon VH5 transcripts from three unrelated patients with atopic dermatitis

    Science.gov (United States)

    1993-01-01

    We have analyzed the nucleotide sequences of 19 epsilon VH5 transcripts derived from in vivo isotype switched peripheral blood B cells of three patients with atopic dermatitis. Comparison with the patients' own germline VH5 gene segments revealed that the epsilon transcripts were derived from both functional members of the human VH5 gene family and harbored numerous somatic mutations (range 5-36 per VH5 gene). In two patients, we detected clonally related but diverged transcripts, permitting the construction of a genealogical tree in one patient. We observed a high proportion of shared silent (S) and replacement (R) mutations among epsilon VH5 sequences derived from all three individuals, even among transcripts descending from the two different germline VH5 gene segments. A remarkably high number of these mutations is shared with previously reported VH5 genes encoding antibodies with defined specificities. The shared S mutations, and likely a fraction of the R mutations, appear to mark preferential sites ("hot spots") of somatic hypermutations in human VH5 genes. The distribution of R and S mutations over complementarity determining region and framework regions in the majority of VH regions deviated from that characteristic of antigen-driven immune response. We hypothesize that the V regions of immunoglobulin E-bearing B cells have accumulated "selectively neutral" mutations over extended periods of clonal expansion, resulting in unusual R/S ratios. We propose that the molecular characteristics of the epsilon VH regions in atopic dermatitis may be representative of antigens that recurrently or chronically stimulate the immune system. PMID:8418213

  3. Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors

    DEFF Research Database (Denmark)

    Goriely, Anne; Hansen, Ruth M S; Taylor, Indira B;

    2009-01-01

    cells that show a paternal age effect. Screening of 30 spermatocytic seminomas for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 (both 1948A>G, encoding K650E, which causes thanatophoric dysplasia in the germline) and 5 mutations in HRAS. Massively parallel sequencing of sperm DNA...... showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the Lys650 codon is similar to that observed in bladder cancer. Most spermatocytic seminomas show increased immunoreactivity for FGFR3 and/or HRAS. We propose that paternal age-effect mutations activate...

  4. Ashkenazi Parkinson's disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries.

    Science.gov (United States)

    Bar-Shira, Anat; Hutter, Carolyn M; Giladi, Nir; Zabetian, Cyrus P; Orr-Urtreger, Avi

    2009-10-01

    The LRRK2 G2019S mutation is a major genetic determinant of Parkinson's disease (PD) across the world that occurs at an elevated frequency in Ashkenazi Jews. We determined the LRRK2 haplotypes in 77 G2019S carriers, mostly Ashkenazi Jews, and in 50 noncarrier Ashkenazi PD patients, using 16 genetic markers. A single haplotype was detected in all mutation carriers, indicating that these individuals share a common founder. Using a maximum-likelihood method, we estimate that Ashkenazi Jews with G2019S share a common ancestor who lived approximately 1,830 (95% CI 1,560-2,160) years ago, around the second century, after the second Jewish Diaspora.

  5. Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway.

    Science.gov (United States)

    Lee, Kyu-Sun; Wu, Zhihao; Song, Yan; Mitra, Siddhartha S; Feroze, Abdullah H; Cheshier, Samuel H; Lu, Bingwei

    2013-12-15

    The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.

  6. A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ) p.Thr124Met mutation shares the Belgian haplotype.

    Science.gov (United States)

    Leal, Alejandro; Berghoff, Corinna; Berghoff, Martin; Rojas-Araya, Melissa; Carolina, Ortiz; Heuss, Dieter; Del Valle, Gerardo; Rautenstrauss, Bernd

    2014-12-01

    The p.Thr124Met mutation in the myelin protein zero (MPZ) causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers' sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch), the founder effect hypothesis for this allele migration is suggestive.

  7. A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ p.Thr124Met mutation shares the Belgian haplotype

    Directory of Open Access Journals (Sweden)

    Alejandro Leal

    2014-12-01

    Full Text Available The p.Thr124Met mutation in the myelin protein zero (MPZ causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers´ sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch, the founder effect hypothesis for this allele migration is suggestive. Rev. Biol. Trop. 62 (4: 1285-1293. Epub 2014 December 01.

  8. Shared ACVR1 mutations in FOP and DIPG: Opportunities and challenges in extending biological and clinical implications across rare diseases.

    Science.gov (United States)

    Han, Harry J; Jain, Payal; Resnick, Adam C

    2017-08-02

    Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation. Here, we discuss cross-fertilization between the FOP and DIPG fields, focusing on the biological mechanisms and principles gleaned from FOP that can be applied to DIPG biology. We highlight our current knowledge of ACVR1 in both diseases, and then describe the growing opportunities and barriers to effectively investigate ACVR1 in DIPG. Importantly, learning from other seemingly unrelated diseases harboring similar mutations may uncover novel mechanisms or processes for future investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Antiaging Properties of a Grape-Derived Antioxidant Are Regulated by Mitochondrial Balance of Fusion and Fission Leading to Mitophagy Triggered by a Signaling Network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN

    Directory of Open Access Journals (Sweden)

    Somak Das

    2014-01-01

    Full Text Available It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the activation of mitochondrial fission and mitophagy. Confocal microscopy conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission electron microscopy. Western blot analyses data are consistent with the results of confocal microscopy. It appears that the grape-derived antioxidant modifies the intracellular environment by changing the oxidizing milieu into a reducing milieu and upregulating intracellular glutathione, potentiates a signal transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial fusion fission-mitophagy that leads to cardioprotection, and paves the way to an anti-aging environment.

  10. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

    Directory of Open Access Journals (Sweden)

    Suleiman H Suleiman

    2015-09-01

    Full Text Available The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6. NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins.

  11. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways.

    Science.gov (United States)

    Suleiman, Suleiman H; Koko, Mahmoud E; Nasir, Wafaa H; Elfateh, Ommnyiah; Elgizouli, Ubai K; Abdallah, Mohammed O E; Alfarouk, Khalid O; Hussain, Ayman; Faisal, Shima; Ibrahim, Fathelrahamn M A; Romano, Maurizio; Sultan, Ali; Banks, Lawrence; Newport, Melanie; Baralle, Francesco; Elhassan, Ahmed M; Mohamed, Hiba S; Ibrahim, Muntaser E

    2015-01-01

    The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins.

  12. De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome

    DEFF Research Database (Denmark)

    Suls, Arvid; Jaehn, Johanna A; Kecskés, Angela

    2013-01-01

    Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet......-syndrome-affected individuals without an SCN1A mutation (these included some atypical cases with onset at up to 2 years of age) by using whole-exome sequencing in proband-parent trios. In two individuals, we identified a de novo loss-of-function mutation in CHD2 (encoding chromodomain helicase DNA binding protein 2). A third...... CHD2 mutation was identified in an epileptic proband of a second (stage 2) cohort. All three individuals with a CHD2 mutation had intellectual disability and fever-sensitive generalized seizures, as well as prominent myoclonic seizures starting in the second year of life or later. To explore...

  13. Pathogenic mutations in Parkinson disease.

    Science.gov (United States)

    Tan, Eng-King; Skipper, Lisa M

    2007-07-01

    Parkinson disease (PD; Parkinson's) is the second most common neurodegenerative disease, characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies. Increasing evidence suggests that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system (UPS) dysfunction may represent the principal molecular pathways that commonly underlie the pathogenesis. The relative role of genetic and environmental factors has been the focus of research and debate. The recent discovery of a number of disease-causing genes (SNCA, Parkin/PARK2, UCHL1, PINK1, DJ1/PARK7, and LRRK2) in familial and sporadic forms of PD has provided considerable insights into the pathophysiology of this complex disorder. The frequency of these gene mutations may vary according to ethnicity and to the specific gene. A gene dosage effect is observed in some cases, and the phenotype of some of the mutation carriers closely resembles typical PD. Penetrance of some of the recurrent mutations is incomplete and may vary with age. Further research to unravel the etiopathology could identify biochemical or genetic markers for potential neuroprotective trials. (c) 2007 Wiley-Liss, Inc.

  14. Shared lives, shared energy

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, P.; Goss, K.

    1982-07-01

    A social experiment in Denmark is described in which 25 families combine private ownership (each family owns its own home) and collectivism (each family owns 1/25 of the grounds, large common house and other facilities). The superinsulated individual homes are small (< 1000 ft/sup 2/) but the common house (7800 ft/sup 2/) provides dining and meeting facilities for all 25 families as well as a central heating plant. Heat may be supplied from solar, wind and/or oil-fired boiler. Adequate hot water storage is provided using solar collectors and a 55 kW Vesta wind generator (surplus power is sold). All south facing roof surfaces are fitted with solar collectors (4455 ft/sup 2/ total). A total of 70% of the energy used is produced on site (solar and wind). The manner of living and sharing (child care, automobiles, cooking, etc.) is described as well as typical floor plans for the units. Other collective housing in Denmark is described and it is postulated that overdrevet may serve as a model. (MJJ)

  15. Sharing Economy

    DEFF Research Database (Denmark)

    Marton, Attila; Constantiou, Ioanna; Thoma, Antonela

    De spite the hype the notion of the sharing economy is surrounded by, our understanding of sharing is surprisingly undertheorized. In this paper, we make a first step towards rem edying this state of affairs by analy sing sharing as a s ocial practice. Based on a multi ple - case study, we analyse...... the institutional assemblage of sharing on online platforms to counter the prevalent assumpti o n i n the literature that sharing derives primarily from the shareability of goods and resources. Sharing, we contend, is a fundament al human practice that, in our case study, takes the particular form of coord inated...

  16. Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria*

    Science.gov (United States)

    Kim, Hyunjin; Yang, Jinsung; Kim, Min Ju; Choi, Sekyu; Chung, Ju-Ryung; Kim, Jong-Min; Yoo, Young Hyun; Chung, Jongkyeong; Koh, Hyongjong

    2016-01-01

    TRAP1 (tumor necrosis factor receptor-associated protein 1), a mitochondrial Hsp90 family chaperone, has been identified as a critical regulator of cell survival and bioenergetics in tumor cells. To discover novel signaling networks regulated by TRAP1, we generated Drosophila TRAP1 mutants. The mutants successfully developed into adults and produced fertile progeny, showing that TRAP1 is dispensable in development and reproduction. Surprisingly, mutation or knockdown of TRAP1 markedly enhanced Drosophila survival under oxidative stress. Moreover, TRAP1 mutation ameliorated mitochondrial dysfunction and dopaminergic (DA) neuron loss induced by deletion of a familial Parkinson disease gene PINK1 (Pten-induced kinase 1) in Drosophila. Gamitrinib-triphenylphosphonium, a mitochondria-targeted Hsp90 inhibitor that increases cell death in HeLa and MCF7 cells, consistently inhibited cell death induced by oxidative stress and mitochondrial dysfunction induced by PINK1 mutation in mouse embryonic fibroblast cells and DA cell models such as SH-SY5Y and SN4741 cells. Additionally, gamitrinib-triphenylphosphonium also suppressed the defective locomotive activity and DA neuron loss in Drosophila PINK1 null mutants. In further genetic analyses, we showed enhanced expression of Thor, a downstream target gene of transcription factor FOXO, in TRAP1 mutants. Furthermore, deletion of FOXO almost nullified the protective roles of TRAP1 mutation against oxidative stress and PINK1 mutation. These results strongly suggest that inhibition of the mitochondrial chaperone TRAP1 generates a retrograde cell protective signal from mitochondria to the nucleus in a FOXO-dependent manner. PMID:26631731

  17. Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria.

    Science.gov (United States)

    Kim, Hyunjin; Yang, Jinsung; Kim, Min Ju; Choi, Sekyu; Chung, Ju-Ryung; Kim, Jong-Min; Yoo, Young Hyun; Chung, Jongkyeong; Koh, Hyongjong

    2016-01-22

    TRAP1 (tumor necrosis factor receptor-associated protein 1), a mitochondrial Hsp90 family chaperone, has been identified as a critical regulator of cell survival and bioenergetics in tumor cells. To discover novel signaling networks regulated by TRAP1, we generated Drosophila TRAP1 mutants. The mutants successfully developed into adults and produced fertile progeny, showing that TRAP1 is dispensable in development and reproduction. Surprisingly, mutation or knockdown of TRAP1 markedly enhanced Drosophila survival under oxidative stress. Moreover, TRAP1 mutation ameliorated mitochondrial dysfunction and dopaminergic (DA) neuron loss induced by deletion of a familial Parkinson disease gene PINK1 (Pten-induced kinase 1) in Drosophila. Gamitrinib-triphenylphosphonium, a mitochondria-targeted Hsp90 inhibitor that increases cell death in HeLa and MCF7 cells, consistently inhibited cell death induced by oxidative stress and mitochondrial dysfunction induced by PINK1 mutation in mouse embryonic fibroblast cells and DA cell models such as SH-SY5Y and SN4741 cells. Additionally, gamitrinib-triphenylphosphonium also suppressed the defective locomotive activity and DA neuron loss in Drosophila PINK1 null mutants. In further genetic analyses, we showed enhanced expression of Thor, a downstream target gene of transcription factor FOXO, in TRAP1 mutants. Furthermore, deletion of FOXO almost nullified the protective roles of TRAP1 mutation against oxidative stress and PINK1 mutation. These results strongly suggest that inhibition of the mitochondrial chaperone TRAP1 generates a retrograde cell protective signal from mitochondria to the nucleus in a FOXO-dependent manner. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Sharing Economy

    DEFF Research Database (Denmark)

    Marton, Attila; Constantiou, Ioanna; Thoma, Antonela

    De spite the hype the notion of the sharing economy is surrounded by, our understanding of sharing is surprisingly undertheorized. In this paper, we make a first step towards rem edying this state of affairs by analy sing sharing as a s ocial practice. Based on a multi ple - case study, we analyse...

  19. Sharing City

    DEFF Research Database (Denmark)

    This magazine offers an insight into the growing commercial innovation, civic movements, and political narratives surrounding sharing economy services, solutions and organisational types. It presents a cross-section of the manifold sharing economy services and solutions that can be found in Denmark....... Solutions of sharing that seeks to improve our cities and local communities in both urban and rural environments. 24 sharing economy organisations and businesses addressing urban and rural issues are being portrayed and seven Danish municipalities that have explored the potentials of sharing economy....... Moreover, 15 thought leading experts - professionals and academic - have been invited to give their perspective on sharing economy for cities. This magazine touches upon aspects of the sharing economy as mobility, communities, sustainability, business development, mobility, and urban-rural relation....

  20. Sharing code

    OpenAIRE

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  1. File sharing

    NARCIS (Netherlands)

    van Eijk, N.

    2011-01-01

    ‘File sharing’ has become generally accepted on the Internet. Users share files for downloading music, films, games, software etc. In this note, we have a closer look at the definition of file sharing, the legal and policy-based context as well as enforcement issues. The economic and cultural impact

  2. Shared leadership

    DEFF Research Database (Denmark)

    Ulhøi, John Parm; Müller, Sabine

    2012-01-01

    The aim of this paper is twofold. First, this paper comprehensively will review the conceptual and empirical literature to identify such critical underlying mechanisms which enable shared or collective leadership. Second, this article identifies the antecedents and outcomes of shared leadership...... according to the literature review to develop a re-conceptualised and synthesized framework for managing the organizational issues associated with shared leadership on various organizational levels. The paper rectifies this by identifying the critical factors and mechanisms which enable shared leadership...... and its antecedents and outcomes, and to develop a re-conceptualized and synthesized framework of shared leadership. The paper closes with a brief discussion of avenues for future research and implications for managers....

  3. Sharing Graphs

    CERN Document Server

    Sahasranand, K R

    2010-01-01

    Almost all known secret sharing schemes work on numbers. Such methods will have difficulty in sharing graphs since the number of graphs increases exponentially with the number of nodes. We propose a secret sharing scheme for graphs where we use graph intersection for reconstructing the secret which is hidden as a sub graph in the shares. Our method does not rely on heavy computational operations such as modular arithmetic or polynomial interpolation but makes use of very basic operations like assignment and checking for equality, and graph intersection can also be performed visually. In certain cases, the secret could be reconstructed using just pencil and paper by authorised parties but cannot be broken by an adversary even with unbounded computational power. The method achieves perfect secrecy for (2, n) scheme and requires far fewer operations compared to Shamir's algorithm. The proposed method could be used to share objects such as matrices, sets, plain text and even a heterogeneous collection of these. S...

  4. Shared leadership

    DEFF Research Database (Denmark)

    Ulhøi, John Parm; Müller, Sabine

    2012-01-01

    The aim of this paper is twofold. First, this paper comprehensively will review the conceptual and empirical literature to identify such critical underlying mechanisms which enable shared or collective leadership. Second, this article identifies the antecedents and outcomes of shared leadership...... according to the literature review to develop a re-conceptualised and synthesized framework for managing the organizational issues associated with shared leadership on various organizational levels. The paper rectifies this by identifying the critical factors and mechanisms which enable shared leadership...... and its antecedents and outcomes, and to develop a re-conceptualized and synthesized framework of shared leadership. The paper closes with a brief discussion of avenues for future research and implications for managers....

  5. Shared Attention.

    Science.gov (United States)

    Shteynberg, Garriy

    2015-09-01

    Shared attention is extremely common. In stadiums, public squares, and private living rooms, people attend to the world with others. Humans do so across all sensory modalities-sharing the sights, sounds, tastes, smells, and textures of everyday life with one another. The potential for attending with others has grown considerably with the emergence of mass media technologies, which allow for the sharing of attention in the absence of physical co-presence. In the last several years, studies have begun to outline the conditions under which attending together is consequential for human memory, motivation, judgment, emotion, and behavior. Here, I advance a psychological theory of shared attention, defining its properties as a mental state and outlining its cognitive, affective, and behavioral consequences. I review empirical findings that are uniquely predicted by shared-attention theory and discuss the possibility of integrating shared-attention, social-facilitation, and social-loafing perspectives. Finally, I reflect on what shared-attention theory implies for living in the digital world.

  6. Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    The concept of knowledge management has, indeed, become a buzzword that every single organization is expected to practice and live by. Knowledge management is about managing the organization's knowledge for the common good of the organization -but practicing knowledge management is not as simple...... as that. This article focuses on knowledge sharing as the process seeking to reduce the resources spent on reinventing the wheel.The article introduces the concept of time sensitiveness; i.e. that knowledge is either urgently needed, or not that urgently needed. Furthermore, knowledge sharing...... is considered as either a push or pull system. Four strategies for sharing knowledge - help, post-it, manuals and meeting, and advice are introduced. Each strategy requires different channels for sharing knowledge. An empirical analysis in a production facility highlights how the strategies can be practiced....

  7. Sharing values, sharing a vision

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-31

    Teamwork, partnership and shared values emerged as recurring themes at the Third Technology Transfer/Communications Conference. The program drew about 100 participants who sat through a packed two days to find ways for their laboratories and facilities to better help American business and the economy. Co-hosts were the Lawrence Livermore National Laboratory and the Lawrence Berkeley Laboratory, where most meetings took place. The conference followed traditions established at the First Technology Transfer/Communications Conference, conceived of and hosted by the Pacific Northwest Laboratory in May 1992 in Richmond, Washington, and the second conference, hosted by the National Renewable Energy Laboratory in January 1993 in Golden, Colorado. As at the other conferences, participants at the third session represented the fields of technology transfer, public affairs and communications. They came from Department of Energy headquarters and DOE offices, laboratories and production facilities. Continued in this report are keynote address; panel discussion; workshops; and presentations in technology transfer.

  8. Shared Memories?

    DEFF Research Database (Denmark)

    Wæhrens, Anne

    2011-01-01

    This paper analyses how the memory of the Holocaust has been addressed in the European Parliament from 1989 to 2009. I identify two major changes that occurred in the 1990s and after the 2004 enlargement of the European Union respectively. In the 1990s the war in Bosnia and the question of restit......This paper analyses how the memory of the Holocaust has been addressed in the European Parliament from 1989 to 2009. I identify two major changes that occurred in the 1990s and after the 2004 enlargement of the European Union respectively. In the 1990s the war in Bosnia and the question...... of restitution universalised the memory of the Holocaust and made it present. The 2004 enlargement brought the memory of Soviet Communism into the Union and made it a central task to construct a community of memory that includes both the memory of the Holocaust and of Soviet Communism. The analysis also...... identifies what seems to be a political memory split between Left and Right; and it shows that the time might not be ripe for a shared European memory....

  9. Element sharing in interleaved antenna arrays

    CSIR Research Space (South Africa)

    Du Plessis, WP

    2012-03-01

    Full Text Available to obtain improved solutions and have been successfully applied to a wide variety of problems. These problems include thinned- 2 Start Stop Initialisation Selection Crossover Terminate?Y N Fitness calculation Penalty Repair Mutation Fig. 1. A... 40 50 60 70 80 90 Filling factor (% ) Shared elements Thinned Inverse Subarray 1 Subarray 2 Fig. 5. The filling factor as a function of the number of shared elements for the penalty-function GA results in Fig. 4 other. Additionally...

  10. PRRT2 gene mutations

    Science.gov (United States)

    Gardiner, Alice R.; Bhatia, Kailash P.; Stamelou, Maria; Dale, Russell C.; Kurian, Manju A.; Schneider, Susanne A.; Wali, G.M.; Counihan, Tim; Schapira, Anthony H.; Spacey, Sian D.; Valente, Enza-Maria; Silveira-Moriyama, Laura; Teive, Hélio A.G.; Raskin, Salmo; Sander, Josemir W.; Lees, Andrew; Warner, Tom; Kullmann, Dimitri M.; Wood, Nicholas W.; Hanna, Michael

    2012-01-01

    ABSTRACT Objective: The proline-rich transmembrane protein (PRRT2) gene was recently identified using exome sequencing as the cause of autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) with or without infantile convulsions (IC) (PKD/IC syndrome). Episodic neurologic disorders, such as epilepsy, migraine, and paroxysmal movement disorders, often coexist and are thought to have a shared channel-related etiology. To investigate further the frequency, spectrum, and phenotype of PRRT2 mutations, we analyzed this gene in 3 large series of episodic neurologic disorders with PKD/IC, episodic ataxia (EA), and hemiplegic migraine (HM). Methods: The PRRT2 gene was sequenced in 58 family probands/sporadic individuals with PKD/IC, 182 with EA, 128 with HM, and 475 UK and 96 Asian controls. Results: PRRT2 genetic mutations were identified in 28 out of 58 individuals with PKD/IC (48%), 1/182 individuals with EA, and 1/128 individuals with HM. A number of loss-of-function and coding missense mutations were identified; the most common mutation found was the p.R217Pfs*8 insertion. Males were more frequently affected than females (ratio 52:32). There was a high proportion of PRRT2 mutations found in families and sporadic cases with PKD associated with migraine or HM (10 out of 28). One family had EA with HM and another large family had typical HM alone. Conclusions: This work expands the phenotype of mutations in the PRRT2 gene to include the frequent occurrence of migraine and HM with PKD/IC, and the association of mutations with EA and HM and with familial HM alone. We have also extended the PRRT2 mutation type and frequency in PKD and other episodic neurologic disorders. PMID:23077024

  11. Calreticulin Mutations in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Noa Lavi

    2014-10-01

    Full Text Available With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph− myeloproliferative neoplasms (MPNs in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET and primary myelofibrosis (PMF. At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations and recurrent 5-bp insertions (type 2 mutations in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review.

  12. Haplotype sharing test maps genes for familial cardiomyopathies

    NARCIS (Netherlands)

    van der Zwaag, P. A.; van Tintelen, J. P.; Gerbens, F.; Jongbloed, J. D. H.; Boven, L. G.; van der Smagt, J. J.; van der Roest, W. P.; van Langen, I. M.; Bikker, H.; Hauer, R. N. W.; van den Berg, M. P.; Hofstra, R. M. W.; te Meerman, Gerhardus

    2011-01-01

    Identifying a mutation in a heterogeneous disease such as inherited cardiomyopathy is a challenge because classical methods, like linkage analysis, can often not be applied as there are too few meioses between affected individuals. However, if affected individuals share the same causal mutation, the

  13. Share your Sweets

    DEFF Research Database (Denmark)

    Byrnit, Jill; Høgh-Olesen, Henrik; Makransky, Guido

    2015-01-01

    as sharing in which group members were allowed to co-feed or remove food from the stock of the food possessor, and the introduction of high-value food resulted in more sharing, not less. Food sharing behavior differed between species in that chimpanzees displayed significantly more begging behavior than......All over the world, humans (Homo sapiens) display resource-sharing behavior, and common patterns of sharing seem to exist across cultures. Humans are not the only primates to share, and observations from the wild have long documented food sharing behavior in our closest phylogenetic relatives......, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, few controlled studies have been made where groups of Pan are introduced to food items that may be shared or monopolized by a first food possessor, and very few studies have examined what happens to these sharing patterns if the food...

  14. Urban sharing culture

    DEFF Research Database (Denmark)

    Fjalland, Emmy Laura Perez

    In urban areas sharing cultures, services and economies are rising. People share, rent and recycle their homes, cars, bikes, rides, tools, cloths, working space, knowhow and so on. The sharing culture can be understood as mobilities (Kesselring and Vogl 2013) of goods, values and ideas reshaping...... our cities. The sharing economy has the power to democratise access the urban space, resources and raw materials (Steen Nielsen 2008; Harvey 2000); it holds the ability to change the current dominant understandings and structures of economy and growth (Steen Nielsen 2008); solve emerging environmental...... and trust. (Thomsen 2013; Bauman 2000; Beck 1992; Giddens 1991). The sharing economy is currently hyper trendy but before claiming capitalism as dead we need to understand the basics of the sharing economies and cultures asking who can share and what will we share. Furthermore it is crucial to study what...

  15. Satisfaction and 'comparison sharing'

    DEFF Research Database (Denmark)

    Amilon, Anna

    2009-01-01

    the probability of satisfaction. Results show that comparison sharing impacts satisfaction for women, and that those women who share more equally than their peers are more likely to be satisfied, whereas comparison sharing has no influence on satisfaction for men. Also, parents are less likely to be satisfied...

  16. Using functional genomics to study PINK1 and metabolic physiology

    DEFF Research Database (Denmark)

    Scheele, Camilla; Larsson, Ola; Timmons, James A

    2009-01-01

    in mammalian cells. Use of such technologies, inspired by nature's endogenous RNAi mechanism-microRNA targeting, comes with significant caveats. While the discipline of Pharmacology taught us last century that inhibitor action specificity is dependent on the concentration used, these experiences have been......Genome sequencing projects have provided the substrate for an unimaginable number of biological experiments. Further, genomic technologies such as microarrays and quantitative and exquisitely sensitive techniques such as real-time quantitative polymerase chain reaction have made it possible...... or experimental control. Thus, functional genomics is now being applied to study metabolic physiology with varying degrees of success. From the genome sequencing projects we also have the information needed to design chemical tools that can knock down a gene transcript, even distinguishing between splice variants...

  17. PINK1 deficiency enhances autophagy and mitophagy induction

    NARCIS (Netherlands)

    Gómez-Sánchez, Rubén; Yakhine-Diop, Sokhna M S; Bravo-San Pedro, José M; Pizarro-Estrella, Elisa; Rodríguez-Arribas, Mario; Climent, Vicente; Martin-Cano, Francisco E; González-Soltero, María E; Tandon, Anurag; Fuentes, José M; González-Polo, Rosa A

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder with poorly understood etiology. Increasing evidence suggests that age-dependent compromise of the maintenance of mitochondrial function is a key risk factor. Several proteins encoded by PD-related genes are associated with mitochondria

  18. PINK1 deficiency enhances autophagy and mitophagy induction

    NARCIS (Netherlands)

    Gómez-Sánchez, Rubén; Yakhine-Diop, Sokhna M S; Bravo-San Pedro, José M; Pizarro-Estrella, Elisa; Rodríguez-Arribas, Mario; Climent, Vicente; Martin-Cano, Francisco E; González-Soltero, María E; Tandon, Anurag; Fuentes, José M; González-Polo, Rosa A

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder with poorly understood etiology. Increasing evidence suggests that age-dependent compromise of the maintenance of mitochondrial function is a key risk factor. Several proteins encoded by PD-related genes are associated with mitochondria includ

  19. The Sharing Economy

    DEFF Research Database (Denmark)

    Avital, Michel; Carroll, John M.; Hjalmarsson, Anders

    2015-01-01

    The sharing economy is spreading rapidly worldwide in a number of industries and markets. The disruptive nature of this phenomenon has drawn mixed responses ranging from active conflict to adoption and assimilation. Yet, in spite of the growing attention to the sharing economy, we still do not know...... much about it. With the abundant enthusiasm about the benefits that the sharing economy can unleash and the weekly reminders about its dark side, further examination is required to determine the potential of the sharing economy while mitigating its undesirable side effects. The panel will join...... the ongoing debate about the sharing economy and contribute to the discourse with insights about how digital technologies are critical in shaping this turbulent ecosystem. Furthermore, we will define an agenda for future research on the sharing economy as it becomes part of the mainstream society as well...

  20. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....

  1. Facilitating Knowledge Sharing

    DEFF Research Database (Denmark)

    Holdt Christensen, Peter

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating...... and the intermediaries regulating the exchange, and facilitating knowledge sharing should therefore be viewed as a continuum of practices under the influence of opportunistic behaviour, obedience or organizational citizenship behaviour. Keywords: Knowledge sharing, motivation, organizational settings, situations...

  2. Facilitating Knowledge Sharing

    OpenAIRE

    Holdt Christensen, Peter

    2005-01-01

    Abstract This paper argues that knowledge sharing can be conceptualized as different situations of exchange in which individuals relate to each other in different ways, involving different rules, norms and traditions of reciprocity regulating the exchange. The main challenge for facilitating knowledge sharing is to ensure that the exchange is seen as equitable for the parties involved, and by viewing the problems of knowledge sharing as motivational problems situated in different organization...

  3. A Data Sharing Story

    Directory of Open Access Journals (Sweden)

    Mercè Crosas

    2012-01-01

    Full Text Available From the early days of modern science through this century of Big Data, data sharing has enabled some of the greatest advances in science. In the digital age, technology can facilitate more effective and efficient data sharing and preservation practices, and provide incentives for making data easily accessible among researchers. At the Institute for Quantitative Social Science at Harvard University, we have developed an open-source software to share, cite, preserve, discover and analyze data, named the Dataverse Network. We share here the project’s motivation, its growth and successes, and likely evolution.

  4. Phenomenology of experiential sharing

    DEFF Research Database (Denmark)

    León, Felipe; Zahavi, Dan

    2016-01-01

    The chapter explores the topic of experiential sharing by drawing on the early contributions of the phenomenologists Alfred Schutz and Gerda Walther. It is argued that both Schutz and Walther support, from complementary perspectives, an approach to experiential sharing that has tended...... to be overlooked in current debates. This approach highlights specific experiential interrelations taking place among individuals who are jointly engaged and located in a common environment, and situates this type of sharing within a broader and richer spectrum of sharing phe- nomena. Whereas Schutz’ route...

  5. Phenomenology of experiential sharing

    DEFF Research Database (Denmark)

    León, Felipe; Zahavi, Dan

    2016-01-01

    The chapter explores the topic of experiential sharing by drawing on the early contributions of the phenomenologists Alfred Schutz and Gerda Walther. It is argued that both Schutz and Walther support, from complementary perspectives, an approach to experiential sharing that has tended to be overl......The chapter explores the topic of experiential sharing by drawing on the early contributions of the phenomenologists Alfred Schutz and Gerda Walther. It is argued that both Schutz and Walther support, from complementary perspectives, an approach to experiential sharing that has tended...

  6. Most parsimonious haplotype allele sharing determination

    Directory of Open Access Journals (Sweden)

    Xu Jiaofen

    2009-04-01

    Full Text Available Abstract Background The "common disease – common variant" hypothesis and genome-wide association studies have achieved numerous successes in the last three years, particularly in genetic mapping in human diseases. Nevertheless, the power of the association study methods are still low, in particular on quantitative traits, and the description of the full allelic spectrum is deemed still far from reach. Given increasing density of single nucleotide polymorphisms available and suggested by the block-like structure of the human genome, a popular and prosperous strategy is to use haplotypes to try to capture the correlation structure of SNPs in regions of little recombination. The key to the success of this strategy is thus the ability to unambiguously determine the haplotype allele sharing status among the members. The association studies based on haplotype sharing status would have significantly reduced degrees of freedom and be able to capture the combined effects of tightly linked causal variants. Results For pedigree genotype datasets of medium density of SNPs, we present two methods for haplotype allele sharing status determination among the pedigree members. Extensive simulation study showed that both methods performed nearly perfectly on breakpoint discovery, mutation haplotype allele discovery, and shared chromosomal region discovery. Conclusion For pedigree genotype datasets, the haplotype allele sharing status among the members can be deterministically, efficiently, and accurately determined, even for very small pedigrees. Given their excellent performance, the presented haplotype allele sharing status determination programs can be useful in many downstream applications including haplotype based association studies.

  7. The Sharing Economy

    DEFF Research Database (Denmark)

    Avital, Michel; Carroll, John M.; Hjalmarsson, Anders;

    2015-01-01

    The sharing economy is spreading rapidly worldwide in a number of industries and markets. The disruptive nature of this phenomenon has drawn mixed responses ranging from active conflict to adoption and assimilation. Yet, in spite of the growing attention to the sharing economy, we still do not kn...

  8. Limitations to sharing entanglement

    CERN Document Server

    Kim, Jeong San; Sanders, Barry C

    2011-01-01

    We discuss limitations to sharing entanglement known as monogamy of entanglement. Our pedagogical approach commences with simple examples of limited entanglement sharing for pure three-qubit states and progresses to the more general case of mixed-state monogamy relations with multiple qudits.

  9. 5G Spectrum Sharing

    OpenAIRE

    Nekovee, Maziar; Rudd, Richard

    2017-01-01

    In this paper an overview is given of the current status of 5G industry standards, spectrum allocation and use cases, followed by initial investigations of new opportunities for spectrum sharing in 5G using cognitive radio techniques, considering both licensed and unlicensed scenarios. A particular attention is given to sharing millimeter-wave frequencies, which are of prominent importance for 5G.

  10. Shared Parenting Dysfunction.

    Science.gov (United States)

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  11. Exploring the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    tensions experience by sharing platforms by looking at the case of mobile fashion reselling and swapping markets. The final paper combines the perspectives of different sharing economy stakeholders and outlines some of the micro and macro tensions arising in and influencing the organization of these multi...... and to provide a more nuanced understanding of the micro- and macro-level tensions that characterize the sharing economy. This thesis consists of four research papers, each using different literature, methodology, and data sets. The first paper investigates how the sharing economy is diffused and is ‘talked...... into existence’ by the communicative acts of a number of different actors. The second paper looks at how the reality of these narratives is actually experienced by the representatives of one type of sharing platform, i.e., fashion libraries. The third paper further expands the understanding of micro-level...

  12. Exploring the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    Despite the growing interest on the part of proponents and opponents - ranging from business, civil society, media, to policy-makers alike - there is still limited knowledge about the working mechanisms of the sharing economy. The thesis is dedicated to explore this understudied phenomenon...... and to provide a more nuanced understanding of the micro- and macro-level tensions that characterize the sharing economy. This thesis consists of four research papers, each using different literature, methodology, and data sets. The first paper investigates how the sharing economy is diffused and is ‘talked......-level tensions experience by sharing platforms by looking at the case of mobile fashion reselling and swapping markets. The final paper combines the perspectives of different sharing economy stakeholders and outlines some of the micro and macro tensions arising in and influencing the organization of these multi...

  13. Chimpanzees share forbidden fruit.

    Directory of Open Access Journals (Sweden)

    Kimberley J Hockings

    Full Text Available The sharing of wild plant foods is infrequent in chimpanzees, but in chimpanzee communities that engage in hunting, meat is frequently used as a 'social tool' for nurturing alliances and social bonds. Here we report the only recorded example of regular sharing of plant foods by unrelated, non-provisioned wild chimpanzees, and the contexts in which these sharing behaviours occur. From direct observations, adult chimpanzees at Bossou (Republic of Guinea, West Africa very rarely transferred wild plant foods. In contrast, they shared cultivated plant foods much more frequently (58 out of 59 food sharing events. Sharing primarily consists of adult males allowing reproductively cycling females to take food that they possess. We propose that hypotheses focussing on 'food-for-sex and -grooming' and 'showing-off' strategies plausibly account for observed sharing behaviours. A changing human-dominated landscape presents chimpanzees with fresh challenges, and our observations suggest that crop-raiding provides adult male chimpanzees at Bossou with highly desirable food commodities that may be traded for other currencies.

  14. Scalp fibroblasts have a shared expression profile in monogenic craniosynostosis

    OpenAIRE

    2009-01-01

    Background Craniosynostosis can be caused by both genetic and environmental factors, the relative contributions of which vary between patients. Genetic testing identifies a pathogenic mutation or chromosomal abnormality in ∼21% of cases, but it is likely that further causative mutations remain to be discovered. Objective To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients w...

  15. Knowledge grows when shared

    DEFF Research Database (Denmark)

    Elbæk, Mikael Karstensen

    2010-01-01

    Knowledge is one of the few commodities that don’t devalue when used. Actually knowledge grows when shared and the free online access to peer-reviewed scientific publications is a potent ingredient the process of sharing. The sharing of knowledge is facilitated by the Open Access Movement. However...... infrastructure for Open Access was launched in Ghent, Belgium. This project and initiative is facilitating the success of the Open Access Pilot in FP7 as presented earlier in this journal. In this brief article I will present some of the most interesting issues that were discussed during the first session...

  16. Global resource sharing

    CERN Document Server

    Frederiksen, Linda; Nance, Heidi

    2011-01-01

    Written from a global perspective, this book reviews sharing of library resources on a global scale. With expanded discovery tools and massive digitization projects, the rich and extensive holdings of the world's libraries are more visible now than at any time in the past. Advanced communication and transmission technologies, along with improved international standards, present a means for the sharing of library resources around the globe. Despite these significant improvements, a number of challenges remain. Global Resource Sharing provides librarians and library managers with a comprehensive

  17. Too Much Information Sharing?

    DEFF Research Database (Denmark)

    Ganuza, Juan José; Jansen, Jos

    2013-01-01

    By using general information structures and precision criteria based on the dispersion of conditional expectations, we study how oligopolists’ information acquisition decisions may change the effects of information sharing on the consumer surplus. Sharing information about individual cost...... parameters gives the following trade-off in Cournot oligopoly. On the one hand, it decreases the expected consumer surplus for a given information precision, as the literature shows. On the other hand, information sharing increases the firms’ incentives to acquire information, and the consumer surplus...... increases in the precision of the firms’ information. Interestingly, the latter effect may dominate the former effect....

  18. Getting Behind B Shares

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    China Ocean Shipping(Group)Co.(COSCO) employs an experimental strategy of making acquisitions through the purchase of B shares COSCO Pacific Ltd.and its affili- ated companies held 4.5 million shares of China International Marine Containers(Grouo)Co.Ltd.(CIMC) as of March 6. Four months ago,the board of direc- tors of COSCO Container Industries Ltd. (COSCO Container)decided to buy more B shares of CIMC through the securities mar- ket.COSCO Container is a shell company registered in the British Virgin Islands with a

  19. Shared decision making

    Science.gov (United States)

    ... the rest of your life Having major surgery Getting genetic or cancer screening tests Talking together about your options helps your provider know how you feel and what you value. How Shared Decision Making Works When facing a decision, your ...

  20. Sharing resources@CERN

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    The library is launching a 'sharing resources@CERN' campaign, aiming to increase the library's utility by including the thousands of books bought by individual groups at CERN. This will improve sharing of information among CERN staff and users. Photo 01: L. to r. Eduardo Aldaz, from the PS division, Corrado Pettenati, Head Librarian, and Isabel Bejar, from the ST division, read their divisional copies of the same book.

  1. The Tradable Shares Puzzle

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A huge number of restricted shares were made tradable in March in the mainland stock market,testing the capability of the fragile capital market Ping An of China has been made the main scapegoat of this year s stock market plunge.A month after its refinancing plan announcement- equivalent to recreating a new Ping An- its 3.12 billion restricted shares were made tradable on March 3,accounting for almost

  2. Performing the sharing economy.

    OpenAIRE

    Richardson, L

    2015-01-01

    The sharing economy converges around activities facilitated through digital platforms that enable peer-to-peer access to goods and services. It constitutes an apparent paradox, framed as both part of the capitalist economy and as an alternative. This duplicity necessitates focusing on the performances of the sharing economy: how it simultaneously constructs diverse economic activities whilst also inviting the deconstruction of ongoing practices of dominance. Such performances hold open the qu...

  3. Regulating the sharing economy

    Directory of Open Access Journals (Sweden)

    Kristofer Erickson

    2016-06-01

    Full Text Available In this introductory essay, we explore definitions of the ‘sharing economy’, a concept indicating both social (relational, communitarian and economic (allocative, profit-seeking aspects which appear to be in tension. We suggest combining the social and economic logics of the sharing economy to focus on the central features of network enabled, aggregated membership in a pool of offers and demands (for goods, services, creative expressions. This definition of the sharing economy distinguishes it from other related peer-to-peer and collaborative forms of production. Understanding the social and economic motivations for and implications of participating in the sharing economy is important to its regulation. Each of the papers in this special issue contributes to knowledge by linking the social and economic aspects of sharing economy practices to regulatory norms and mechanisms. We conclude this essay by suggesting future research to further clarify and render intelligible the sharing economy, not as a contradiction in terms but as an empirically observable realm of socio-economic activity.

  4. Information partnerships--shared data, shared scale.

    Science.gov (United States)

    Konsynski, B R; McFarlan, F W

    1990-01-01

    How can one company gain access to another's resources or customers without merging ownership, management, or plotting a takeover? The answer is found in new information partnerships, enabling diverse companies to develop strategic coalitions through the sharing of data. The key to cooperation is a quantum improvement in the hardware and software supporting relational databases: new computer speeds, cheaper mass-storage devices, the proliferation of fiber-optic networks, and networking architectures. Information partnerships mean that companies can distribute the technological and financial exposure that comes with huge investments. For the customer's part, partnerships inevitably lead to greater simplification on the desktop and more common standards around which vendors have to compete. The most common types of partnership are: joint marketing partnerships, such as American Airline's award of frequent flyer miles to customers who use Citibank's credit card; intraindustry partnerships, such as the insurance value-added network service (which links insurance and casualty companies to independent agents); customer-supplier partnerships, such as Baxter Healthcare's electronic channel to hospitals for medical and other equipment; and IT vendor-driven partnerships, exemplified by ESAB (a European welding supplies and equipment company), whose expansion strategy was premised on a technology platform offered by an IT vendor. Partnerships that succeed have shared vision at the top, reciprocal skills in information technology, concrete plans for an early success, persistence in the development of usable information for all partners, coordination on business policy, and a new and imaginative business architecture.

  5. Labia Majora Share

    Science.gov (United States)

    Lee, Hanjing; Yap, Yan Lin; Low, Jeffrey Jen Hui

    2017-01-01

    Defects involving specialised areas with characteristic anatomical features, such as the nipple, upper eyelid, and lip, benefit greatly from the use of sharing procedures. The vulva, a complex 3-dimensional structure, can also be reconstructed through a sharing procedure drawing upon the contralateral vulva. In this report, we present the interesting case of a patient with chronic, massive, localised lymphedema of her left labia majora that was resected in 2011. Five years later, she presented with squamous cell carcinoma over the left vulva region, which is rarely associated with chronic lymphedema. To the best of our knowledge, our management of the radical vulvectomy defect with a labia majora sharing procedure is novel and has not been previously described. The labia major flap presented in this report is a shared flap; that is, a transposition flap based on the dorsal clitoral artery, which has consistent vascular anatomy, making this flap durable and reliable. This procedure epitomises the principle of replacing like with like, does not interfere with leg movement or patient positioning, has minimal donor site morbidity, and preserves other locoregional flap options for future reconstruction. One limitation is the need for a lax contralateral vulva. This labia majora sharing procedure is a viable option in carefully selected patients. PMID:28194353

  6. Shared care (comanagement).

    Science.gov (United States)

    Montero Ruiz, E

    2016-01-01

    Surgical departments have increasing difficulties in caring for their hospitalised patients due to the patients' advanced age and comorbidity, the growing specialisation in medical training and the strong political-healthcare pressure that a healthcare organisation places on them, where surgical acts take precedence over other activities. The pressure exerted by these departments on the medical area and the deficient response by the interconsultation system have led to the development of a different healthcare organisation model: Shared care, which includes perioperative medicine. In this model, 2 different specialists share the responsibility and authority in caring for hospitalised surgical patients. Internal Medicine is the most appropriate specialty for shared care. Internists who exercise this responsibility should have certain characteristics and must overcome a number of concerns from the surgeon and anaesthesiologist. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  7. Sharing big biomedical data.

    Science.gov (United States)

    Toga, Arthur W; Dinov, Ivo D

    The promise of Big Biomedical Data may be offset by the enormous challenges in handling, analyzing, and sharing it. In this paper, we provide a framework for developing practical and reasonable data sharing policies that incorporate the sociological, financial, technical and scientific requirements of a sustainable Big Data dependent scientific community. Many biomedical and healthcare studies may be significantly impacted by using large, heterogeneous and incongruent datasets; however there are significant technical, social, regulatory, and institutional barriers that need to be overcome to ensure the power of Big Data overcomes these detrimental factors. Pragmatic policies that demand extensive sharing of data, promotion of data fusion, provenance, interoperability and balance security and protection of personal information are critical for the long term impact of translational Big Data analytics.

  8. CF Mutation Panel

    Science.gov (United States)

    ... Testing; Cystic Fibrosis Transmembrane Conductance Regulator Mutation Analysis; CFTR Mutation Analysis Formal name: Cystic Fibrosis Gene Mutation ... an elevated immunoreactive trypsinogen (IRT) or positive sweat chloride test , to confirm the diagnosis of cystic fibrosis. ...

  9. Sharing the dance -

    DEFF Research Database (Denmark)

    He, Jing; Ravn, Susanne

    2017-01-01

    to the highly specialized field of elite sports dance, we aim at exploring the way in which reciprocity unfolds in intensive deliberate practices of movement. In our analysis, we specifically argue that the ongoing dynamics of two separate flows of movement constitute a shared experience of dancing together....... In this sense, moving together, in sports dance, is a practical way of understanding each other. In agreement with Zahavi, our analysis emphasizes the bi-directed nature of sharing. However, at the same time, we contribute to Zahavi’s ongoing endeavour as the special case of sports dance reveals how reciprocity...

  10. Towards A Shared Mission

    DEFF Research Database (Denmark)

    Staunstrup, Jørgen; Orth Gaarn-Larsen, Carsten

    A mission shared by stakeholders, management and employees is a prerequisite for an engaging dialog about the many and substantial changes and challenges currently facing universities. Too often this essen-tial dialog reveals mistrust and misunderstandings about the role and outcome of the univer......A mission shared by stakeholders, management and employees is a prerequisite for an engaging dialog about the many and substantial changes and challenges currently facing universities. Too often this essen-tial dialog reveals mistrust and misunderstandings about the role and outcome...

  11. Shared values and normality

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-hua; PANG Xue-cheng

    2006-01-01

    This paper investigates the relationship between the normality and the shared values for a meromorphic function on the unit disc △.Based on Marty's normality criterion and through a detailed analysis of the meromorphic functions,it is shown that if for every f∈F,f and f(k) share a and b on △ and the zeros of f(z)-a are of multiplicity k≥3,then F is normal on △,where F is a family of meromorphic functions on the unit disc △,and a and b are distinct values.

  12. Molecular methods for the detection of mutations.

    Science.gov (United States)

    Monteiro, C; Marcelino, L A; Conde, A R; Saraiva, C; Giphart-Gassler, M; De Nooij-van Dalen, A G; Van Buuren-van Seggelen, V; Van der Keur, M; May, C A; Cole, J; Lehmann, A R; Steinsgrimsdottir, H; Beare, D; Capulas, E; Armour, J A

    2000-01-01

    We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.

  13. SharedSpaces mingle

    NARCIS (Netherlands)

    Handberg, L.; Gullström, C.; Kort, J.; Nyström, J.

    2016-01-01

    SharedSpaces is a WebRTC design prototype that creates a virtual media space where people can mingle and interact. Although you are in different locations, you appear side by side in front of a chosen backdrop. This interactive installation addresses spatial and social connectedness, stressing the

  14. Shared goals and development

    DEFF Research Database (Denmark)

    Blomberg, Olle

    2015-01-01

    undemanding for children to engage in, and therefore has the potential to play a part in fostering their understanding of other minds. Part of the functional role of shared goals is to enable agents to choose means that are appropriate to realising a goal with others rather than individually. By offering...

  15. Shared Oral Care

    DEFF Research Database (Denmark)

    Hede, Børge; Elmelund Poulsen,, Johan; Christophersen, Rasmus

    2014-01-01

    Shared Oral Care - Forebyggelse af orale sygdomme på plejecentre Introduktion og formål: Mangelfuld mundhygiejne hos plejekrævende ældre er et alment og veldokumenteret sundhedsproblem, der kan føre til massiv udvikling af tandsygdomme, og som yderligere kan være medvirkende årsag til alvorlige...

  16. Shared Care in Diabetes?

    DEFF Research Database (Denmark)

    Bødker, Keld

    2006-01-01

    The Danish National Board of Health has recently released a report that is intended to mark the start of a new project to establish it support for shared care in diabetes. In this paper I raise a number of concerns where lack of attention towards participation from prospective users constitute...

  17. Sharing Expertise: Consulting

    Science.gov (United States)

    Graves, Bill

    2011-01-01

    A special breed of superintendents who have developed expertise in a particular area find ways of sharing it in other venues as outside consultants. They pull extra duty to put their special skills into practice, to give back to their communities, to stay current and grounded in the field, or to enhance their professional reputations. They teach…

  18. 'Smart Power' for' Sharing'

    Institute of Scientific and Technical Information of China (English)

    Wang Ting

    2010-01-01

    @@ As an attitude of life The Interstoff Asia Essential Spring will be held from March 17th to 19th,2010,in Hong Kong Convention & Exhibition Centre.During this exhibition,the Interstoff Asia Directions trend committee will present its apparel fabric trend forecast for next season's wardrobes,unfolding a story of'Smart Power' of 'Sharing'.

  19. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...

  20. Promoting teachers’ knowledge sharing

    NARCIS (Netherlands)

    Runhaar, P.R.; Sanders, K.

    2016-01-01

    Teachers’ professional development is nowadays seen as key in efforts to improve education. Knowledge sharing is a learning activity with which teachers not only professionalize themselves, but contribute to the professional development of their colleagues as well. This paper presents two studies,

  1. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...

  2. Sharing Research Results

    Science.gov (United States)

    Ashbrook, Peggy

    2011-01-01

    There are many ways to share a collection of data and students' thinking about that data. Explaining the results of science inquiry is important--working scientists and amateurs both contribute information to the body of scientific knowledge. Students can collect data about an activity that is already happening in a classroom (e.g., the qualities…

  3. Promoting teachers’ knowledge sharing

    NARCIS (Netherlands)

    Runhaar, P.R.; Sanders, K.

    2016-01-01

    Teachers’ professional development is nowadays seen as key in efforts to improve education. Knowledge sharing is a learning activity with which teachers not only professionalize themselves, but contribute to the professional development of their colleagues as well. This paper presents two studies, a

  4. Share the Fruits

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Procter & Gamble Co,extends its employee stock ownership plan to benefit its Chinese employees The Procter & Gamble Co.(P&G) launched its Chinese employee stock ownership plan(ESOP)on April 1 after five years of preparation.The plan entitles its more than 7,000 employees in China to buy P&G stocks and share its growth benefits.

  5. Beyond processor sharing

    NARCIS (Netherlands)

    Aalto, S.; Ayesta, U.; Borst, S.C.; Misra, V.; Núñez Queija, R.

    2007-01-01

    While the (Egalitarian) Processor-Sharing (PS) discipline offers crucial insights in the performance of fair resource allocation mechanisms, it is inherently limited in analyzing and designing differentiated scheduling algorithms such as Weighted Fair Queueing and Weighted Round-Robin. The Discrimin

  6. Power Sharing Courts

    Directory of Open Access Journals (Sweden)

    Stefan Graziadei

    2016-06-01

    Full Text Available In this paper, I introduce a novel concept, the one of power sharing courts. Scholars of judicial politics look at the reasons behind judicial selection and the patterns of decision making within courts through the lens of ideology (left-right. However, the resulting fertile scholarly analysis has not been extended to divided societies, where the main cleavages are not partisan but ethno-national. In these societies, the liberal model of selecting judges and taking decisions within an apex court is often corrected to specifically include politically salient ascriptive cleavages (such as ethnicity/nationality/language/religion. The main thrust of my argument is that there is a model of selecting judges, taking decisions and sharing posts of influence within apex courts in divided societies that has not yet been conceptually captured: power sharing courts. In analogy to consociationalism in the political system, power sharing in the judiciary aims to solve salient inter-community conflicts by including all relevant groups in these bodies on a basis of parity or proportionality. The paper is of equal interest to scholars of constitutional courts, consociationalists, comparatists, as well as country specialists.

  7. The Sharing Economy

    DEFF Research Database (Denmark)

    Hamari, Juho; Sjöklint, Mimmi; Ukkonen, Antti

    2016-01-01

    Information and communications technologies (ICTs) have enabled the rise of so-called “Collaborative Consumption” (CC): the peer-to-peer-based activity of obtaining, giving, or sharing the access to goods and services, coordinated through community-based online services. CC has been expected...

  8. Promoting teachers’ knowledge sharing

    NARCIS (Netherlands)

    Runhaar, P.R.; Sanders, K.

    2016-01-01

    Teachers’ professional development is nowadays seen as key in efforts to improve education. Knowledge sharing is a learning activity with which teachers not only professionalize themselves, but contribute to the professional development of their colleagues as well. This paper presents two studies, a

  9. Policy enabled information sharing system

    Science.gov (United States)

    Jorgensen, Craig R.; Nelson, Brian D.; Ratheal, Steve W.

    2014-09-02

    A technique for dynamically sharing information includes executing a sharing policy indicating when to share a data object responsive to the occurrence of an event. The data object is created by formatting a data file to be shared with a receiving entity. The data object includes a file data portion and a sharing metadata portion. The data object is encrypted and then automatically transmitted to the receiving entity upon occurrence of the event. The sharing metadata portion includes metadata characterizing the data file and referenced in connection with the sharing policy to determine when to automatically transmit the data object to the receiving entity.

  10. Genomic sharing surrounding alleles identical by descent : Effects of genetic drift and population growth

    NARCIS (Netherlands)

    te Meerman, G J; Van der Meulen, M A

    1997-01-01

    The number of identical deleterious mutations present in a population may become very large, depending on the combined effect of genetic drift, population growth and limited negative selection. The distribution of the length of the shared area between two random chromosomes carrying the mutations ha

  11. Genomic sharing surrounding alleles identical by descent : Effects of genetic drift and population growth

    NARCIS (Netherlands)

    te Meerman, G J; Meulen ,van der Martin

    1997-01-01

    The number of identical deleterious mutations present in a population may become very large, depending on the combined effect of genetic drift, population growth and limited negative selection. The distribution of the length of the shared area between two random chromosomes carrying the mutations ha

  12. Shared care and boundaries:

    DEFF Research Database (Denmark)

    Winthereik, Brit Ross

    2008-01-01

    and technology studies. Findings – The paper shows how a version of “the responsible patient” emerges from the project which is different from the version envisioned by the project organisation. The emerging one is concerned with the boundary between primary and secondary sector care, and not with the boundary...... of healthcare in relation to IT design. Originality/value – The paper shows that “unshared” care does not exist; care is always shared among human and nonhuman actors. It also points to the value of studying how boundaries are enacted in projects that seek to create continuity across boundaries. Udgivelsesdato......Purpose – The paper seeks to examine how an online maternity record involving pregnant women worked as a means to create shared maternity care. Design/methodology/approach – Ethnographic techniques have been used. The paper adopts a theoretical/methodological framework based on science...

  13. Shared goals and development

    DEFF Research Database (Denmark)

    Blomberg, Olle

    2015-01-01

    In 'Joint Action and Development', Stephen Butterfill argues that if several agents' actions are driven by what he calls a "shared goal" -- a certain pattern of goal-relations and expectations -- then these actions constitute a joint action. This kind of joint action is sufficiently cognitively...... undemanding for children to engage in, and therefore has the potential to play a part in fostering their understanding of other minds. Part of the functional role of shared goals is to enable agents to choose means that are appropriate to realising a goal with others rather than individually. By offering...... a counterexample, I show that the pattern of goal-relations and expectations specified by Butterfill cannot play this role. I then provide an appropriately conceptually and cognitively undemanding amendment with which the account can be saved....

  14. Does Knowledge Sharing Pay?

    DEFF Research Database (Denmark)

    Mahnke, Volker; Pedersen, Torben; Venzin, Markus

    This empirical paper explores knowledge outflow from MNC subsidiaries and its impact on the MNC performance. We develop and test hypotheses derived from literature on MNC knowledge flows integrated with the perspective of knowledge-creating, self-interested MNC subsidiaries. The hypotheses...... are developed using a simultaneous equation model applied to a unique dataset encompassing a German MNC, HeidelbergCement. Enablers and impediments of knowledge outflows are assessed in order to explain why subsidiaries share their knowledge with other MNC units. Implications are examined by studying the link...... between knowledge outflows and subsidiary performance. Our findings suggest that knowledge outflows increase a subsidiary's performance only up to a certain point and that too much knowledge sharing may be detrimental to the contributing subsidiary's performance....

  15. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  16. Does Knowledge Sharing Pay?

    DEFF Research Database (Denmark)

    Mahnke, Volker; Pedersen, Torben; Venzin, Markus

    This empirical paper explores knowledge outflow from MNC subsidiaries and its impact on the MNC performance. We develop and test hypotheses derived from literature on MNC knowledge flows integrated with the perspective of knowledge-creating, self-interested MNC subsidiaries. The hypotheses are de...... between knowledge outflows and subsidiary performance. Our findings suggest that knowledge outflows increase a subsidiary's performance only up to a certain point and that too much knowledge sharing may be detrimental to the contributing subsidiary's performance....

  17. Sharing data increases citations

    DEFF Research Database (Denmark)

    Drachen, Thea Marie; Ellegaard, Ole; Larsen, Asger Væring

    2016-01-01

    This paper presents some indications to the existence of a citation advantage related to sharing data using astrophysics as a case. Through bibliometric analyses we find a citation advantage for astrophysical papers in core journals. The advantage arises as indexed papers are associated with data...... by bibliographical links, and consists of papers receiving on average significantly more citations per paper per year, than do papers not associated with links to data....

  18. Sharing resources@CERN

    CERN Multimedia

    2002-01-01

    The library is launching a 'sharing resources@CERN' campaign, aiming to increase the library's utility by including the thousands of books bought by individual groups at CERN. This will improve sharing of information among CERN staff and users. Until now many people were unaware that copies of the same book (or standard, or journal) are often held not only by the library but by different divisions. (Here Eduardo Aldaz, from the PS division, and Isabel Bejar, from the ST division, read their divisional copies of the same book.) The idea behind the library's new sharing resources@CERN' initiative is not at all to collect the books in individual collections at the CERN library, but simply to register them in the Library database. Those not belonging to the library will in principle be unavailable for loan, but should be able to be consulted by anybody at CERN who is interested. "When you need a book urgently and it is not available in the library,' said PS Division engineer Eduardo Aldaz Carroll, it is a sham...

  19. Bonobos share with strangers.

    Directory of Open Access Journals (Sweden)

    Jingzhi Tan

    Full Text Available Humans are thought to possess a unique proclivity to share with others--including strangers. This puzzling phenomenon has led many to suggest that sharing with strangers originates from human-unique language, social norms, warfare and/or cooperative breeding. However, bonobos, our closest living relative, are highly tolerant and, in the wild, are capable of having affiliative interactions with strangers. In four experiments, we therefore examined whether bonobos will voluntarily donate food to strangers. We show that bonobos will forego their own food for the benefit of interacting with a stranger. Their prosociality is in part driven by unselfish motivation, because bonobos will even help strangers acquire out-of-reach food when no desirable social interaction is possible. However, this prosociality has its limitations because bonobos will not donate food in their possession when a social interaction is not possible. These results indicate that other-regarding preferences toward strangers are not uniquely human. Moreover, language, social norms, warfare and cooperative breeding are unnecessary for the evolution of xenophilic sharing. Instead, we propose that prosociality toward strangers initially evolves due to selection for social tolerance, allowing the expansion of individual social networks. Human social norms and language may subsequently extend this ape-like social preference to the most costly contexts.

  20. Fixed Access Network Sharing

    Science.gov (United States)

    Cornaglia, Bruno; Young, Gavin; Marchetta, Antonio

    2015-12-01

    Fixed broadband network deployments are moving inexorably to the use of Next Generation Access (NGA) technologies and architectures. These NGA deployments involve building fiber infrastructure increasingly closer to the customer in order to increase the proportion of fiber on the customer's access connection (Fibre-To-The-Home/Building/Door/Cabinet… i.e. FTTx). This increases the speed of services that can be sold and will be increasingly required to meet the demands of new generations of video services as we evolve from HDTV to "Ultra-HD TV" with 4k and 8k lines of video resolution. However, building fiber access networks is a costly endeavor. It requires significant capital in order to cover any significant geographic coverage. Hence many companies are forming partnerships and joint-ventures in order to share the NGA network construction costs. One form of such a partnership involves two companies agreeing to each build to cover a certain geographic area and then "cross-selling" NGA products to each other in order to access customers within their partner's footprint (NGA coverage area). This is tantamount to a bi-lateral wholesale partnership. The concept of Fixed Access Network Sharing (FANS) is to address the possibility of sharing infrastructure with a high degree of flexibility for all network operators involved. By providing greater configuration control over the NGA network infrastructure, the service provider has a greater ability to define the network and hence to define their product capabilities at the active layer. This gives the service provider partners greater product development autonomy plus the ability to differentiate from each other at the active network layer.

  1. Shared clinical decision making

    Science.gov (United States)

    AlHaqwi, Ali I.; AlDrees, Turki M.; AlRumayyan, Ahmad; AlFarhan, Ali I.; Alotaibi, Sultan S.; AlKhashan, Hesham I.; Badri, Motasim

    2015-01-01

    Objectives: To determine preferences of patients regarding their involvement in the clinical decision making process and the related factors in Saudi Arabia. Methods: This cross-sectional study was conducted in a major family practice center in King Abdulaziz Medical City, Riyadh, Saudi Arabia, between March and May 2012. Multivariate multinomial regression models were fitted to identify factors associated with patients preferences. Results: The study included 236 participants. The most preferred decision-making style was shared decision-making (57%), followed by paternalistic (28%), and informed consumerism (14%). The preference for shared clinical decision making was significantly higher among male patients and those with higher level of education, whereas paternalism was significantly higher among older patients and those with chronic health conditions, and consumerism was significantly higher in younger age groups. In multivariate multinomial regression analysis, compared with the shared group, the consumerism group were more likely to be female [adjusted odds ratio (AOR) =2.87, 95% confidence interval [CI] 1.31-6.27, p=0.008] and non-dyslipidemic (AOR=2.90, 95% CI: 1.03-8.09, p=0.04), and the paternalism group were more likely to be older (AOR=1.03, 95% CI: 1.01-1.05, p=0.04), and female (AOR=2.47, 95% CI: 1.32-4.06, p=0.008). Conclusion: Preferences of patients for involvement in the clinical decision-making varied considerably. In our setting, underlying factors that influence these preferences identified in this study should be considered and tailored individually to achieve optimal treatment outcomes. PMID:26620990

  2. Mobile energy sharing futures

    DEFF Research Database (Denmark)

    Worgan, Paul; Knibbe, Jarrod; Plasencia, Diego Martinez

    2016-01-01

    We foresee a future where energy in our mobile devices can be shared and redistributed to suit our current task needs. Many of us are beginning to carry multiple mobile devices and we seek to re-evaluate the traditional view of a mobile device as only accepting energy. In our vision, we can...... leverage the energy stored in our devices to wirelessly distribute energy between our friends, family, colleagues and strangers devices. In this paper we explore the opportunities and interactions presented by such spontaneous energy transfer interactions and present some envisaged collaborative energy...

  3. Sharing Keynote Slideshows

    CERN Document Server

    Clark, Josh

    2010-01-01

    Slideshows have come a long way since overhead projectors were your only option. You can show share your ideas with the world via email, DVD, PDF, YouTube, iPhone, or kiosk. Once your show is polished to perfection, this thorough, accessible guide shows you how to export and deliver it all possible ways-even as a PowerPoint file, QuickTime movie, or web site. As a bonus, you'll find advice on setting up your equipment and delivering an effective presentation.

  4. VHA Data Sharing Agreement Repository

    Data.gov (United States)

    Department of Veterans Affairs — The VHA Data Sharing Agreement Repository serves as a centralized location to collect and report on agreements that share VHA data with entities outside of VA. It...

  5. BOREL'S DIRECTIONS AND SHARED VALUES

    Institute of Scientific and Technical Information of China (English)

    Qingcai ZHANG

    2013-01-01

    In this article,we study the problems of Borel's directions of meromorphic functions concerning shared values and prove that if two meromorphic functions of infinite order share three distinct values,their Borel's directions are same.

  6. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Shared consultant physician posts.

    LENUS (Irish Health Repository)

    Cooke, J

    2012-01-31

    Our aim was to assess the acceptability and cost-efficiency of shared consultancy posts. Two consultant physicians worked alternate fortnights for a period of twelve months. Questionnaires were distributed to general practitioners, nurses, consultants and junior doctors affected by the arrangement. Patients or their next of kin were contacted by telephone. 1\\/17 of consultants described the experience as negative. 14\\/19 junior doctors reported a positive experience. 11 felt that training had been improved while 2 felt that it had been adversely affected. 17\\/17 GPs were satisfied with the arrangement. 1\\/86 nurses surveyed reported a negative experience. 1\\/48 patients were unhappy with the arrangement. An extra 2.2 (p<0.001) patients were seen per clinic. Length of stay was shortened by 2.49 days (p<0.001). A saving of 69,212 was made due to decreased locum requirements. We present data suggesting structured shared consultancy posts can be broadly acceptable and cost efficient in Ireland.

  8. Shared Consumption : A Technological Analysis

    OpenAIRE

    John A. Weymark

    2004-01-01

    James Buchanan (Economica, [1966]) has argued that Alfred Marshall's theory of jointly-supplied goods can be extended to analyze the allocation of impure public goods. This article introduces a way of modelling sharing technologies for jointly-supplied goods that captures the essential features of Buchanan's proposal. Public and private goods are special cases of shared goods obtained by appropriately specifying the sharing technology. Necessary conditions for an allocation in a shared goods ...

  9. Competition in the sharing economy

    OpenAIRE

    Demary, Vera

    2015-01-01

    Sharing goods, services or knowledge is at the center of the so-called Sharing Economy. Businesses are usually based on online platforms that match demand and supply which is in many cases, but not always provided by individuals. Sharing Economy companies typically compete with traditional companies in many different markets. The main challenge of this type of competition currently is the application of the existing regulation. While incumbent firms adhere to this, Sharing Economy companies o...

  10. Fractions: How to Fair Share

    Science.gov (United States)

    Wilson, P. Holt; Edgington, Cynthia P.; Nguyen, Kenny H.; Pescosolido, Ryan S.; Confrey, Jere

    2011-01-01

    Children learn from a very early age what it means to get their "fair share." Whether it is candy or birthday cake, many children successfully create equal-size groups or parts of a collection or whole but later struggle to create fair shares of multiple wholes, such as fairly sharing four pies among a family of seven. Recent research suggests…

  11. Transgenic Animal Mutation Assays

    Institute of Scientific and Technical Information of China (English)

    Tao Chen; Ph.D.D.A.B.T.

    2005-01-01

    @@ The novel transgenic mouse and rat mutation assays have provided a tool for analyzing in vivo mutation in any tissue, thus permitting the direct comparison of cancer incidence with mutant frequency.

  12. A common Greenlandic Inuit BRCA1 RING domain founder mutation

    DEFF Research Database (Denmark)

    Hansen, T.v.O.; Ejlertsen, B.; Albrechtsen, Anders;

    2009-01-01

    Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1...... exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight...... of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit...

  13. SHARED TECHNOLOGY TRANSFER PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    GRIFFIN, JOHN M. HAUT, RICHARD C.

    2008-03-07

    The program established a collaborative process with domestic industries for the purpose of sharing Navy-developed technology. Private sector businesses were educated so as to increase their awareness of the vast amount of technologies that are available, with an initial focus on technology applications that are related to the Hydrogen, Fuel Cells and Infrastructure Technologies (Hydrogen) Program of the U.S. Department of Energy. Specifically, the project worked to increase industry awareness of the vast technology resources available to them that have been developed with taxpayer funding. NAVSEA-Carderock and the Houston Advanced Research Center teamed with Nicholls State University to catalog NAVSEA-Carderock unclassified technologies, rated the level of readiness of the technologies and established a web based catalog of the technologies. In particular, the catalog contains technology descriptions, including testing summaries and overviews of related presentations.

  14. Borrowing brainpower - sharing insecurities

    DEFF Research Database (Denmark)

    Wegener, Charlotte; Meier, Ninna; Ingerslev, Karen

    2016-01-01

    Academic writing is a vital, yet complex skill that must be developed within a doctoral training process. In addition, becoming an academic researcher is a journey of changing sense of self and identity. Through analysis of a group session, we show how the feedback of peers addresses questions...... of structure and writing style along with wider issues of researcher identity. Thus, peer learning is demonstrated as a process of simultaneously building a text and an identity as scholarly researcher. The paper advocates ‘borrowing brainpower’ from peers in order to write better texts and, at the same time......, ‘share insecurities’ during the development of the researcher identity. Based on a distributed notion of peer learning and identity, we point to the need for further research into the everyday activities of doctoral writing groups in order to understand the dynamic relationship between production of text...

  15. Latex allergy and filaggrin null mutations

    DEFF Research Database (Denmark)

    Carlsen, Berit C; Meldgaard, Michael; Hamann, Dathan

    2011-01-01

    Objectives Natural rubber latex (NRL) contains over 200 proteins of which 13 have been identified as allergens and the cause of type I latex allergy. Health care workers share a high occupational risk for developing latex allergy. Filaggrin null mutations increase the risk of type I sensitization...... in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized......Objectives Natural rubber latex (NRL) contains over 200 proteins of which 13 have been identified as allergens and the cause of type I latex allergy. Health care workers share a high occupational risk for developing latex allergy. Filaggrin null mutations increase the risk of type I sensitizations...

  16. Secret Sharing and Proactive Renewal of Shares in Hierarchical Groups

    CERN Document Server

    Naskar, Ruchira; 10.5121/ijcsit.2010.2312

    2010-01-01

    Secret sharing in user hierarchy represents a challenging area for research. Although a lot of work has already been done in this direc- tion, this paper presents a novel approach to share a secret among a hierarchy of users while overcoming the limitations of the already exist- ing mechanisms. Our work is based on traditional (k +1; n)-threshold secret sharing, which is secure as long as an adversary can compromise not more than k secret shares. But in real life it is often feasible for an adversary to obtain more than k shares over a long period of time. So, in our work we also present a way to overcome this vulnerability, while implementing our hierarchical secret sharing scheme. The use of Elliptic Curve Cryptography makes the computations easier and faster in our work.

  17. Maize Mutator transposon

    Institute of Scientific and Technical Information of China (English)

    Yijun WANG; Mingliang XU; Dexiang DENG; Yunlong BIAN

    2008-01-01

    Transposable elements are widely distributed in eukaryotes. Due to its high copy numbers, high forward mutation rate and preferential insertion into low-copy DNA sequences, among others, the Mutator system has been widely used as a mutagen in genomic research. The discovery, classification, transposition specificity and epige-netic regulation of Mutator transposons were described. The application of Mutator tagging in plant genomic research was also presented. The role of Mu-like elements in genome evolution was briefly depicted. Moreover, the direction of Mutator transposon research in the future was discussed.

  18. Data sharing in neuroimaging research

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste ePoline

    2012-04-01

    Full Text Available Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging.

  19. 2012 Information Sharing Environment Performance Data

    Data.gov (United States)

    Information Sharing Environment — This is a survey of federal departments and agencies who share terrorism information and are therefore considered part of the Information Sharing Environment. The...

  20. 2013 Information Sharing Environment Performance Data

    Data.gov (United States)

    Information Sharing Environment — This is a survey of federal departments and agencies who share terrorism information and are therefore considered part of the Information Sharing Environment. The...

  1. SharePoint User's Guide

    CERN Document Server

    Corporation, Infusion Development

    2009-01-01

    This straightforward guide shows SharePoint users how to create and use web sites for sharing and collaboration. Learn to use the document and picture libraries for adding and editing content, add discussion boards and surveys, receive alerts when documents and information have been added or changed, and enhance security. Designed to help you find answers quickly, the book shows how to make the most of SharePoint for productivity and collaboration.

  2. Challenges in sharing information effectively

    DEFF Research Database (Denmark)

    Sonnenwald, Diane H.

    2006-01-01

    were not recognized; implications of relevant information were not shared; differences in the role and expression of emotions when sharing information was not understood; and, the need to reestablish trust was not recognized. Conclusion. The challenges in information sharing identified here may extend...... to other high stress, unique and complex situations, such as natural disasters. Recommendations for more effective information behaviour techniques in dynamic group work situations are presented....

  3. Challenges in sharing information effectively

    DEFF Research Database (Denmark)

    Sonnenwald, Diane H.

    2006-01-01

    Introduction. The goal of information sharing is to change a person's image of the world and to develop a shared working understanding. It is an essential component of collaboration. This paper examines barriers to sharing information effectively in dynamic group work situations. Method. Three...... to other high stress, unique and complex situations, such as natural disasters. Recommendations for more effective information behaviour techniques in dynamic group work situations are presented....

  4. Modeling Shared Variables in VHDL

    DEFF Research Database (Denmark)

    Madsen, Jan; Brage, Jens P.

    1994-01-01

    A set of concurrent processes communicating through shared variables is an often used model for hardware systems. This paper presents three modeling techniques for representing such shared variables in VHDL, depending on the acceptable constraints on accesses to the variables. Also a set of guide......A set of concurrent processes communicating through shared variables is an often used model for hardware systems. This paper presents three modeling techniques for representing such shared variables in VHDL, depending on the acceptable constraints on accesses to the variables. Also a set...

  5. Information Sharing among Untrustworthy Entities

    Science.gov (United States)

    Tamura, Shinsuke; Yanase, Tatsuro

    Most of current technologies that enable secure information sharing assume that entities that share information are mutually trustworthy. However, in recent applications this assumption is not realistic. As applications become sophisticated, information systems are required to share information securely even among untrustworthy entities. This paper discusses two kinds of problems about information sharing among untrustworthy entities, i.e. secure statistical data gathering and anonymous authentication, and proposes their solutions. The former is a problem to calculate statistics while ensuring that raw data are not disclosed to any entity including ones that calculate statistics, and the latter is a problem to authenticate entities while keeping their identities confidential.

  6. Identification of a founder BRCA2 mutation in Sardinia

    Science.gov (United States)

    Pisano, M; Cossu, A; Persico, I; Palmieri, G; Angius, A; Casu, G; Palomba, G; Sarobba, M G; Rocca, P C Ossu; Dedola, M F; Olmeo, N; Pasca, A; Budroni, M; Marras, V; Pisano, A; Farris, A; Massarelli, G; Pirastu, M; Tanda, Francesco

    2000-01-01

    Sardinian population can be instrumental in defining the molecular basis of cancer, using the identity-by-descent method. We selected seven Sardinian breast cancer families originating from the northern-central part of the island with multiple affected members in different generations. We genotyped 106 members of the seven families and 20 control nuclear families with markers flanking BRCA2 locus at 13q12–q13. The detection of a common haplotype shared by four out of seven families (60%) suggests the presence of a founder BRCA2 mutation. Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a ‘frame-shift’ mutation at codon 2867 (8765delAG), causing a premature termination-codon. This mutation was found in breast cancer patients as well as one prostate and one bladder cancer patient with shared haplotype. We then investigated the frequency of 8765delAG in the Sardinian breast cancer population by analysing 270 paraffin-embedded normal tissue samples from breast cancer patients. Five patients (1.7%) were found to be positive for the 8765delAG mutation. Discovery of a founder mutation in Sardinia through the identity-by-descent method demonstrates that this approach can be applied successfully to find mutations either for breast cancer or for other types of tumours. © 2000 Cancer Research Campaign PMID:10682665

  7. Technology Mediated Information Sharing (Monitor Sharing) in Primary Care Encounters

    Science.gov (United States)

    Asan, Onur

    2013-01-01

    The aim of this dissertation study was to identify and describe the use of electronic health records (EHRs) for information sharing between patients and clinicians in primary-care encounters and to understand work system factors influencing information sharing. Ultimately, this will promote better design of EHR technologies and effective training…

  8. Processor-sharing queues and resource sharing in wireless LANs

    NARCIS (Netherlands)

    Cheung, Sing Kwong

    2007-01-01

    In the past few decades, the processor-sharing (PS) model has received considerable attention in the queueing theory community and in the field of performance evaluation of computer and communication systems. The scarce resource is simultaneously shared among all users in these systems. PS models ar

  9. Risk Sharing in Labour Markets

    NARCIS (Netherlands)

    Bigsten, Arne; Collier, Paul; Dercon, Stefan; Fafchamps, Marcel; Gunning, Jan Willem; Oduro, Abena; Oostendorp, Remco; Pattillo, Cathy; Soderbom, Mans; Teal, Francis; Zeufack, Albert

    2003-01-01

    Empirical work in labour economics has focused on rent sharing as an explanation for the observed correlation in cross-sections between wages and profitability. The alternative explanation of risk sharing between workers and employers has not been tested. Using a unique panel data set for four Afric

  10. Resource Sharing in Community Colleges.

    Science.gov (United States)

    Meyer, Frank; Hines, Edward; Lupo, Anita; Ley, Connie

    1998-01-01

    Presents a study analyzing voluntary resource sharing practices in a state population of 49 community colleges. Asserts that while resource sharing has been used primarily to solve short-term needs, it should be integrated in strategic and long-term fiscal planning. (JDI)

  11. The Nominal Share Price Puzzle

    National Research Council Canada - National Science Library

    William C. Weld; Roni Michaely; Richard H. Thaler; Shlomo Benartzi

    2009-01-01

    ... investigate in this paper is whether vestigial norms and customs affect corporate decision making. Consider the following fact: The average nominal price for a share of stock on the New York Stock exchange has remained roughly constant (about $35) since the Great Depression. The mechanism that has allowed share prices to remain remarkably con...

  12. Food Sharing: An Evolutionary Perspective.

    Science.gov (United States)

    Feinman, Saul

    Food altruism and the consumption of food are examined from a sociological perspective which assumes that humans share food as inclusive fitness actors. Inclusive fitness implies the representation of an individual's genes in future generations through his own or others' offspring. The discussion includes characteristics of food sharing among kin…

  13. Knowledge Sharing: Developing from within

    Science.gov (United States)

    Patrick, Keith; Dotsika, Fefie

    2007-01-01

    Purpose: If collaboration and knowledge sharing lie at the core of providing added-value to either services or products can we improve this process? The purpose of this paper is to suggest that it can be improved and this lies in how we develop the systems that support collaboration and knowledge sharing. This can be achieved within the…

  14. Food Sharing: An Evolutionary Perspective.

    Science.gov (United States)

    Feinman, Saul

    Food altruism and the consumption of food are examined from a sociological perspective which assumes that humans share food as inclusive fitness actors. Inclusive fitness implies the representation of an individual's genes in future generations through his own or others' offspring. The discussion includes characteristics of food sharing among kin…

  15. SECTORAL SHARES AND ECONOMIC GROWTH

    DEFF Research Database (Denmark)

    Ahmad, Nisar; Naveed, Amjad; Naz, Amber

    2013-01-01

    In developed countries, the share of services and industrial sector has increased in the past few decades and at the same time the share of agriculture sector went down considerably. In the literature, there exists a debate about structural change in the developed countries. Neoclassical economists...

  16. Work sharing in Kerela's fisheries

    NARCIS (Netherlands)

    Berg, van den M.M.; Lensing, B.J.

    2007-01-01

    Earlier studies suggest that once population growth and market integration reach a certain critical level, traditional practices of work sharing tend to degenerate or disappear altogether. Work sharing has, however, survived to date in small-scale fisheries in Kerala, India. Artisanal fishermen

  17. Governing Individual Knowledge Sharing Behavior

    DEFF Research Database (Denmark)

    Minbaeva, Dana; Pedersen, Torben

    2010-01-01

    The emerging Knowledge Governance Approach asserts the need to build microfoundations grounded in individual action. Toward this goal, using the Theory of Planned Behavior, we aim to explain individual knowledge sharing behavior as being determined by the intention to share knowledge and its...

  18. Three kinds of mutation

    CERN Document Server

    Buan, Aslak Bakke; Thomas, Hugh

    2010-01-01

    For a finite dimensional hereditary algebra, we consider: exceptional sequences in the category of finite dimensional modules, silting objects in the bounded derived category, and m-cluster tilting objects in the m-cluster category. There are mutation operations on both the set of m-cluster tilting objects and the set of exceptional sequences. It is also possible to define a mutation operation for silting objects. We compare these three different notions of mutation.

  19. Down-regulation of B cell-related genes in peripheral blood leukocytes of Parkinson's disease patients with and without GBA mutations.

    Science.gov (United States)

    Kobo, Hila; Bar-Shira, Anat; Dahary, Dvir; Gan-Or, Ziv; Mirelman, Anat; Goldstein, Orly; Giladi, Nir; Orr-Urtreger, Avi

    2016-02-01

    Parkinson's disease (PD) is a common neurodegenerative disorder, caused by aging, genetic and environmental factors. Many genes and genetic loci have been implicated in autosomal dominant and recessive PD, among them SNCA, LRRK2, GBA, Parkin, DJ1 and PINK1. Mutations in the LRRK2 and GBA genes are especially common among PD patients of Ashkenazi-Jewish (AJ) origin, accounting for over a third of the patient population. We aimed to identify genes and cellular pathways that may be involved in GBA-associated PD. Whole genome expression analysis was performed using peripheral blood leukocytes (PBLs) of PD patients with mutations in the GBA gene (PD-GBA, n = 59) compared to healthy controls (n = 59). Significant expression changes were detected in 26 genes, most of them were down-regulated in patients and annotated to B cell or immune-related functions. The expression levels of five membrane-bound B cell genes (FCRL1, CD19, CD22, CD79A and CD180) were further analyzed in four distinct populations: (1) Healthy controls (n = 20), (2) PD-GBA (n = 20), (3) PD patients who do not carry LRRK2 or GBA mutations (PD-NC, n = 20), (4) Asymptomatic 1st degree family members, with (n = 15) or without (n = 15) GBA mutations. In qRT-PCR analysis, all five genes were down-regulated in patients (PD-GBA and PD-NC) compared to controls. These changes in expression were not observed when comparing family members who carry GBA mutations to non-carrier family members. Furthermore, these expression levels were disease-duration dependent: the most significant decreased expression occurred after the first two years of onset, and remained steady after 6 years. These results further support the involvement of B cell-related genes in PD and correlate the level of reduced expression to disease duration.

  20. Knowledge Sharing and National Culture

    DEFF Research Database (Denmark)

    Michailova, Snejina; Hutchings, Kate

    2004-01-01

    Much of the knowledge management literature tends to assume a rather universalistunderstanding of knowledge sharing. Yet, attitudes to knowledge sharing as well as actualknowledge-sharing behaviour depend on conditions that vary across institutional and culturalenvironments. This paper contributes...... to the knowledge-sharing literature by specificallydiscussing the interplay between knowledge-sharing and national cultural factors in the context oftransition countries. The paper engages in a comparative examination of two major transitionsocieties, China and Russia, and contributes to understanding...... the complexity of differencesbetween transition economies. The paper is written as a set of theoretical arguments andpropositions that is designed to elucidate more nuanced ways of thinking about knowledgesharing in China and Russia. We argue that in the case of China and Russia, verticalindividualism...

  1. AKUISISI DAN BUDAYA KNOWLEDGE SHARING

    Directory of Open Access Journals (Sweden)

    Nuril Kusumawardhani Soeprapto Putri

    2011-05-01

    Full Text Available Large companies which are experiencing barriers in innovation often take a radical step to acquire knowledge, namely acquisition. Though innovation is not the only reason, acquisition will result in the company wishes to achieve competitive advantage affected by the creation of ideas, creativity and innovation. The three points can be achieved more easily when the knowledge sharing within the organization / company runs well. However, the acquisition maybe impacts as a counter-attack for the knowledge sharing culture both in the acquisitor and company which obtains the acquisition. Therefore, a key to succeed the acquisition is a sharing culture among individuals within a company that runs well or even better. Individuals from the acquisitor and those of the company that obtains the acquisition can adapt to each other and have confidence in order not to hinder them to share knowledge. This study discusses in detail the potential impacts of an acquisition upon a knowledge sharing culture in a company.

  2. Knowledge Sharing and National Culture

    DEFF Research Database (Denmark)

    Michailova, Snejina; Hutchings, Kate

    2004-01-01

    Much of the knowledge management literature tends to assume a rather universalistunderstanding of knowledge sharing. Yet, attitudes to knowledge sharing as well as actualknowledge-sharing behaviour depend on conditions that vary across institutional and culturalenvironments. This paper contributes...... to the knowledge-sharing literature by specificallydiscussing the interplay between knowledge-sharing and national cultural factors in the context oftransition countries. The paper engages in a comparative examination of two major transitionsocieties, China and Russia, and contributes to understanding...... the complexity of differencesbetween transition economies. The paper is written as a set of theoretical arguments andpropositions that is designed to elucidate more nuanced ways of thinking about knowledgesharing in China and Russia. We argue that in the case of China and Russia, verticalindividualism...

  3. Gestational mutations in radiation carcinogenesis

    Science.gov (United States)

    Meza, R.; Luebeck, G.; Moolgavkar, S.

    Mutations in critical genes during gestation could increase substantially the risk of cancer. We examine the consequences of such mutations using the Luebeck-Moolgavkar model for colorectal cancer and the Lea-Coulson modification of the Luria-Delbruck model for the accumulation of mutations during gestation. When gestational mutation rates are high, such mutations make a significant contribution to cancer risk even for adult tumors. Furthermore, gestational mutations ocurring at distinct times during emryonic developmemt lead to substantially different numbers of mutated cells at birth, with early mutations leading to a large number (jackpots) of mutated cells at birth and mutation occurring late leading to only a few mutated cells. Thus gestational mutations could confer considerable heterogeneity of the risk of cancer. If the fetus is exposed to an environmental mutagen, such as ionizing radiation, the gestational mutation rate would be expected to increase. We examine the consequences of such exposures during gestation on the subsequent development of cancer.

  4. Simulation Analysis of Data Sharing in Shared Memory Multiprocessors

    Science.gov (United States)

    2016-06-14

    Arch86] J. Archibald and J. Baer, "An Evaluation of Cache Coherence So lutions in Shared-Bus Multiprocessors", ACM Transactions on Computer Systen...Agarwal and A. Gupta, "Memory-Refer ence Olaracteristics of Multiprocessor Applications under MACH", Proceedings of the 1 988 ACM Sigmerrics Conference on...Evaluation of Cache Coherence Solutions in Shared-Bus Multiprocessors", ACM Transactions on Computer Systems, 4, 4 (November 1986), 273-298. [Baro85

  5. On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Wang Daoshun

    2010-01-01

    Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

  6. One Share-One Vote

    DEFF Research Database (Denmark)

    Poulsen, Thomas; Eklund, Johan E.

    Shares with more voting rights than cash flow rights provide their owners with a disproportional influence that is often found to destroy the value of outside equity. This is taken as evidence of discretionary use of power. However, concentration of power does not necessarily result from control...... enhancing mechanisms; it could also be that some shareholders retain a large block in a one share-one vote structure. In this paper, we develop a methodology to disentangle disproportionality, which allows us to test the effect of deviations from one share-one vote more precisely. Our empirical findings add...

  7. Knowledge Sharing is Knowledge Creation

    DEFF Research Database (Denmark)

    Greve, Linda

    2015-01-01

    Knowledge sharing and knowledge transfer are important to knowledge communication. However when groups of knowledge workers engage in knowledge communication activities, it easily turns into mere mechanical information processing despite other ambitions. This article relates literature of knowledge...... reducing complexity and dividing knowledge into to dichotomies or hierarchies, knowledge workers should be enabled to use different strategies for knowledge sharing, -transfer and –creation depending on the task and the nature of the knowledge. However if the ambition is to have a strategy for sharing...

  8. Almost-perfect secret sharing

    CERN Document Server

    Kaced, Tarik

    2011-01-01

    Splitting a secret s between several participants, we generate (for each value of s) shares for all participants. The goal: authorized groups of participants should be able to reconstruct the secret but forbidden ones get no information about it. In this paper we introduce several notions of non- perfect secret sharing, where some small information leak is permitted. We study its relation to the Kolmogorov complexity version of secret sharing (establishing some connection in both directions) and the effects of changing the secret size (showing that we can decrease the size of the secret and the information leak at the same time).

  9. i-Review: Sharing Code

    Directory of Open Access Journals (Sweden)

    Jonas Kubilius

    2014-02-01

    Full Text Available Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF. GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  10. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

    DEFF Research Database (Denmark)

    de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah;

    2016-01-01

    BACKGROUND: Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellect...

  11. Mutation and premating isolation.

    Science.gov (United States)

    Woodruff, R C; Thompson, J N

    2002-11-01

    While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

  12. Medicaid Disproportionate Share Hospital Payments

    Data.gov (United States)

    U.S. Department of Health & Human Services — Medicaid Disproportionate Share Hospital (DSH) Payments This link provides you with information about Medicaid DSH Payments. You can find information on DSH Audit...

  13. Information sharing promotes prosocial behaviour

    CERN Document Server

    Szolnoki, Attila

    2013-01-01

    More often than not, bad decisions are bad regardless of where and when they are made. Information sharing might thus be utilized to mitigate them. Here we show that sharing the information about strategy choice between players residing on two different networks reinforces the evolution of cooperation. In evolutionary games the strategy reflects the action of each individual that warrants the highest utility in a competitive setting. We therefore assume that identical strategies on the two networks reinforce themselves by lessening their propensity to change. Besides network reciprocity working in favour of cooperation on each individual network, we observe the spontaneous emerge of correlated behaviour between the two networks, which further deters defection. If information is shared not just between individuals but also between groups, the positive effect is even stronger, and this despite the fact that information sharing is implemented without any assumptions with regards to content.

  14. COAST Map Sharing Plugin Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the development of a capability which will allow ecosystem managers to share a map view in terms of location, magnification level, and data layers (to...

  15. Share capitalism and worker wellbeing().

    Science.gov (United States)

    Bryson, Alex; Clark, Andrew E; Freeman, Richard B; Green, Colin P

    2016-10-01

    We show that worker wellbeing is determined not only by the amount of compensation workers receive but also by how compensation is determined. While previous theoretical and empirical work has often been preoccupied with individual performance-related pay, we find that the receipt of a range of group-performance schemes (profit shares, group bonuses and share ownership) is associated with higher job satisfaction. This holds conditional on wage levels, so that pay methods are associated with greater job satisfaction in addition to that coming from higher wages. We use a variety of methods to control for unobserved individual and job-specific characteristics. We suggest that half of the share-capitalism effect is accounted for by employees reciprocating for the "gift"; we also show that share capitalism helps dampen the negative wellbeing effects of what we typically think of as "bad" aspects of job quality.

  16. Information sharing promotes prosocial behaviour

    Science.gov (United States)

    Szolnoki, Attila; Perc, Matjaž

    2013-05-01

    More often than not, bad decisions are bad regardless of where and when they are made. Information sharing might thus be utilized to mitigate them. Here we show that sharing information about strategy choice between players residing on two different networks reinforces the evolution of cooperation. In evolutionary games, the strategy reflects the action of each individual that warrants the highest utility in a competitive setting. We therefore assume that identical strategies on the two networks reinforce themselves by lessening their propensity to change. Besides network reciprocity working in favour of cooperation on each individual network, we observe the spontaneous emergence of correlated behaviour between the two networks, which further deters defection. If information is shared not just between individuals but also between groups, the positive effect is even stronger, and this despite the fact that information sharing is implemented without any assumptions with regard to content.

  17. Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia.

    Science.gov (United States)

    Ben Brick, Ahlem Sabrine; Laroussi, Nadia; Mesrati, Hela; Kefi, Rym; Bchetnia, Mbarka; Lasram, Khaled; Ben Halim, Nizar; Romdhane, Lilia; Ouragini, Houyem; Marrakchi, Salaheddine; Boubaker, Mohamed Samir; Meddeb Cherif, Mounira; Castiglia, Daniele; Hovnanian, Alain; Abdelhak, Sonia; Turki, Hamida

    2014-05-01

    Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background.

  18. An Image Secret Sharing Method

    Science.gov (United States)

    2006-07-01

    M. E. Hellman, “On secret sharing systems,” vol. IT-29, no. 1, pp. 35–41, Jan. 1983. [10] K. Kurosawa , K. Okada, K. Sakano, W. Ogata, and S. Tsujii...Ed., Berlin, Germany, 1994, pp. 1–12. [14] W. Ogata and K. Kurosawa , “Some ba- sic properties of general nonperfect secret sharing schemes,” J.UCS

  19. Information Sharing and Environmental Policies

    Directory of Open Access Journals (Sweden)

    Nikos Tsakiris

    2010-10-01

    Full Text Available Based on the assumption that in a standard eco-dumping model governments are uncertain about future product demand and allowing governments to obtain information from firms, we examine governments’ and firms’ incentives to share information. We show that when governments regulate polluting firms through emission standards, then governments and firms will reach an agreement concerning information sharing. The opposite holds when governments regulate pollution through emission taxes.

  20. Developing SharePoint applications

    OpenAIRE

    Rupnik, Gašper

    2011-01-01

    The thesis includes a research on SharePoint 2010 programming capabilities and a display of products created by this knowledge. The introduction part includes background information on how the topic was chosen and how the thesis was developed. The second chapter presents the SharePoint platform, which includes a description of its structure, function and usability. The third chapter focuses solely on the programming of the platform. First, some of the most useful software tools for i...

  1. Normal Functions Concerning Shared Values

    Institute of Scientific and Technical Information of China (English)

    WANG XIAO-JING

    2009-01-01

    In this paper we discuss normal functions concerning shared values. We obtain the follow result. Let F be a family of meromorphic functions in the unit disc △, and a be a nonzero finite complex number. If for any f ∈ F, the zeros of f are of multiplicity, f and f' share a, then there exists a positive number M such that for any f ∈ F, (1 -|z|~2)(|f'(z)|)/(1+|f(z)|~2)≤ M.

  2. The value of shared services.

    Science.gov (United States)

    Wallace, Beverly B

    2011-07-01

    A multisite shared services organization, combined with a robust business continuity plan, provides infrastructure and redundancies that mitigate risk for hospital CFOs. These structures can position providers to do the following: move essential operations out of a disaster impact zone, if necessary. Allow resources to focus on immediate patient care needs. Take advantage of economies of scale in temporary staffing. Leverage technology. Share in investments in disaster preparedness and business continuity solutions

  3. Shared Year Exchange in Nursing

    DEFF Research Database (Denmark)

    Vedsegaard, Helle Wendner; Wederkinck, Elisabeth

    2010-01-01

    Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien.......Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien....

  4. Capacity sharing of water reservoirs

    Science.gov (United States)

    Dudley, Norman J.; Musgrave, Warren F.

    1988-05-01

    The concept of a water use property right is developed which does not apply to water volumes as such but to a share of the capacity (not contents) of river storage reservoirs and their inflows. The shareholders can withdraw water from their share over time in accordance with their preferences for stability of water deliveries. The reservoir authority does not manage reservoir releases but keeps record of individual shareholder's withdrawals and net inflows to monitor the quantity of water in each shareholder's capacity share. A surplus of total reservoir contents over the sum of the contents of the individual shareholder's capacity shares will accrue over time. Two different criteria for its periodic distribution among shareholders are compared. A previous paper Dudley (this issue(b)) noted a loss of short-run economic efficiency as reservoir and farm management decision making become separated. This is largely overcome by capacity sharing which allows each user to integrate the management of their portion of the reservoir and their farming operations. The nonattenuated nature of the capacity sharing water rights also promotes long-run economic efficiency.

  5. Mutation rates among RNA viruses

    OpenAIRE

    Drake, John W.; Holland, John J.

    1999-01-01

    The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often lacking. A previous analysis of mutation rates in RNA viru...

  6. 7 CFR 1980.391 - Equity sharing.

    Science.gov (United States)

    2010-01-01

    ... property. Shared equity will be the lesser of the interest assistance granted or the amount of value appreciation available for shared equity. Value appreciation available for shared equity means the market value... amount of shared equity. The RHS approval official will calculate shared equity when a borrower's...

  7. Display Sharing: An Alternative Paradigm

    Science.gov (United States)

    Brown, Michael A.

    2010-01-01

    The current Johnson Space Center (JSC) Mission Control Center (MCC) Video Transport System (VTS) provides flight controllers and management the ability to meld raw video from various sources with telemetry to improve situational awareness. However, maintaining a separate infrastructure for video delivery and integration of video content with data adds significant complexity and cost to the system. When considering alternative architectures for a VTS, the current system's ability to share specific computer displays in their entirety to other locations, such as large projector systems, flight control rooms, and back supporting rooms throughout the facilities and centers must be incorporated into any new architecture. Internet Protocol (IP)-based systems also support video delivery and integration. IP-based systems generally have an advantage in terms of cost and maintainability. Although IP-based systems are versatile, the task of sharing a computer display from one workstation to another can be time consuming for an end-user and inconvenient to administer at a system level. The objective of this paper is to present a prototype display sharing enterprise solution. Display sharing is a system which delivers image sharing across the LAN while simultaneously managing bandwidth, supporting encryption, enabling recovery and resynchronization following a loss of signal, and, minimizing latency. Additional critical elements will include image scaling support, multi -sharing, ease of initial integration and configuration, integration with desktop window managers, collaboration tools, host and recipient controls. This goal of this paper is to summarize the various elements of an IP-based display sharing system that can be used in today's control center environment.

  8. Mitochondrial DNA mutations in mutator mice confer respiration defects and B-cell lymphoma development.

    Directory of Open Access Journals (Sweden)

    Takayuki Mito

    Full Text Available Mitochondrial DNA (mtDNA mutator mice are proposed to express premature aging phenotypes including kyphosis and hair loss (alopecia due to their carrying a nuclear-encoded mtDNA polymerase with a defective proofreading function, which causes accelerated accumulation of random mutations in mtDNA, resulting in expression of respiration defects. On the contrary, transmitochondrial mito-miceΔ carrying mtDNA with a large-scale deletion mutation (ΔmtDNA also express respiration defects, but not express premature aging phenotypes. Here, we resolved this discrepancy by generating mtDNA mutator mice sharing the same C57BL/6J (B6J nuclear background with that of mito-miceΔ. Expression patterns of premature aging phenotypes are very close, when we compared between homozygous mtDNA mutator mice carrying a B6J nuclear background and selected mito-miceΔ only carrying predominant amounts of ΔmtDNA, in their expression of significant respiration defects, kyphosis, and a short lifespan, but not the alopecia. Therefore, the apparent discrepancy in the presence and absence of premature aging phenotypes in mtDNA mutator mice and mito-miceΔ, respectively, is partly the result of differences in the nuclear background of mtDNA mutator mice and of the broad range of ΔmtDNA proportions of mito-miceΔ used in previous studies. We also provided direct evidence that mtDNA abnormalities in homozygous mtDNA mutator mice are responsible for respiration defects by demonstrating the co-transfer of mtDNA and respiration defects from mtDNA mutator mice into mtDNA-less (ρ(0 mouse cells. Moreover, heterozygous mtDNA mutator mice had a normal lifespan, but frequently developed B-cell lymphoma, suggesting that the mtDNA abnormalities in heterozygous mutator mice are not sufficient to induce a short lifespan and aging phenotypes, but are able to contribute to the B-cell lymphoma development during their prolonged lifespan.

  9. Mutations in GABRB3

    DEFF Research Database (Denmark)

    Møller, Rikke S; Wuttke, Thomas V; Helbig, Ingo

    2017-01-01

    OBJECTIVE: To examine the role of mutations in GABRB3 encoding the β3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. METHODS: We performed massive parallel sequencing...... of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs. RESULTS: We identified 22 patients with heterozygous mutations in GABRB3, including 3...... probands from multiplex families. The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy with myoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies...

  10. AIP mutations and gigantism.

    Science.gov (United States)

    Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F; Beckers, Albert

    2017-06-01

    AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated pituitary adenoma (FIPA) kindreds, and patients with macroadenomas who are diagnosed ≤30 years). AIP mutations are most prevalent in patients with pituitary gigantism (29% of this group were found to have mutations in AIP gene). These data support targeted genetic screening for AIP mutations/deletions in these groups of pituitary adenoma patients. Earlier diagnosis of AIP-related acromegaly-gigantism cases enables timely clinical evaluation and treatment, thereby improving outcomes in terms of excessive linear growth and acromegaly comorbidities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Mapping Mutations on Phylogenies

    DEFF Research Database (Denmark)

    Nielsen, Rasmus

    2005-01-01

    This chapter provides a short review of recent methodologies developed for mapping mutations on phylogenies. Mapping of mutations, or character changes in general, using the maximum parsimony principle has been one of the most powerful tools in phylogenetics, and it has been used in a variety...... of different applications, for example, in the detection of correlated evolution and to identify selection acting on DNA sequences. However, many uses of parsimony mappings have been criticized because they focus on only one of many possible mappings and/or because they do not incorporate statistical...... uncertainty in the mapping. Recently developed probabilistic methods can incorporate statistical uncertainty in the character mappings. In these methods, focus is on a probability distribution of mutational mappings instead of a single estimate of the mutational mapping....

  12. Knowledge sharing in diverse organizations

    DEFF Research Database (Denmark)

    Lauring, Jakob; Selmer, Jan

    2012-01-01

    It has been argued that both strengths and weaknesses of diversity in organisations stem from the different demographic, national, linguistic, social and cultural backgrounds of their members. However, few attempts have been made to link different types of diversity to knowledge sharing despite....... As predicted, results showed that diversity related to internationalisation (cultural and linguistic) had more positive associations with knowledge sharing than inherent demographic diversity (age and gender), which generally had negative or no relationships with knowledge sharing. The implications...... the fact that organisations which can make full use of their collective knowledge and expertise could be expected to be more efficient, effective and creative. Therefore, a survey was directed towards 16 diverse academic departments in three large universities in Denmark, and 489 academics took part...

  13. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  14. Content Sharing for Mobile Devices

    CERN Document Server

    Ball, Rudi

    2008-01-01

    The miniaturisation of computing devices has seen computing devices become increasingly pervasive in society. With this increased pervasiveness, the technologies of small computing devices have also improved. Mobile devices are now capable of capturing various forms of multimedia and able to communicate wirelessly using increasing numbers of communication techniques. The owners and creators of local content are motivated to share this content in ever increasing volume; the conclusion has been that social networks sites are seeing a revolution in the sharing of information between communities of people. As load on centralised systems increases, we present a novel decentralised peer-to-peer approach dubbed the Market Contact Protocol (MCP) to achieve cost effective, scalable and efficient content sharing using opportunistic networking (pocket switched networking), incentive, context-awareness, social contact and mobile devices. Within the report we describe how the MCP is simulated with a superimposed geographi...

  15. Availability Cascades & the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2014-01-01

    In search of a new concept that will provide answers to as to how modern societies should not only make sense but also resolve the social and environmental problems linked with our modes of production and consumption, collaborative consumption and the sharing economy are increasingly attracting...... attention. This conceptual paper attempts to explain the emergent focus on the sharing economy and associated business and consumption models by applying cascade theory. Risks associated with this behavior will be especially examined with regard to the sustainability claim of collaborative consumption....... With academics, practitioners, and civil society alike having a shared history in being rather fast in accepting new concepts that will not only provide business opportunities but also a good conscience, this study proposes a critical study of the implications of collaborative consumption, before engaging...

  16. Availability Cascades & the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2015-01-01

    In search of a new concept that will provide answers to as to how modern societies should not only make sense but also resolve the social and environmental problems linked with our modes of production and consumption, collaborative consumption and the sharing economy are increasingly attracting...... attention. This conceptual paper attempts to explain the emergent focus on the sharing economy and associated business and consumption models by applying cascade theory. Risks associated with this behavior will be especially examined with regard to the sustainability claim of collaborative consumption....... With academics, practitioners, and civil society alike having a shared history in being rather fast in accepting new concepts that will not only provide business opportunities but also a good conscience, this study proposes a critical study of the implications of collaborative consumption, before engaging...

  17. Subquivers of mutation-acyclic quivers are mutation-acyclic

    CERN Document Server

    Warkentin, Matthias

    2011-01-01

    Quiver mutation plays a crucial role in the definition of cluster algebras by Fomin and Zelevinsky. It induces an equivalence relation on the set of all quivers without loops and two-cycles. A quiver is called mutation-acyclic if it is mutation-equivalent to an acyclic quiver. The aim of this note is to show that full subquivers of mutation-acyclic quivers are mutation-acyclic.

  18. Knowledge Sharing is Knowledge Creation

    DEFF Research Database (Denmark)

    Greve, Linda

    2015-01-01

    communication and knowledge creation to an intervention study in a large Danish food production company. For some time a specific group of employees uttered a wish for knowledge sharing, but it never really happened. The group was observed and submitted to metaphor analysis as well as analysis of co......-creation strategies. Confronted with the results, the group completely altered their approach to knowledge sharing and let it become knowledge co-creation. The conclusions are, that knowledge is and can only be a diverse and differentiated concept, and that groups are able to embrace this complexity. Thus rather than...

  19. Sharing best practice in partnerships

    DEFF Research Database (Denmark)

    Mosgaard, Mette; Remmen, Arne; Pedersen, Claus Stig

    In this paper, the promotion of sustainable products through the sharing of best practices in product chains is examined. The general understanding is that the interactions in the supply chain are changing from a traditional focus on the supply of goods “just in time” towards a focus on value...... upstream in the supply chain, and “business development” of sustainable products and product service systems. Sharing best practice in partnerships is an example of the latter, but Supply Chain Management goes beyond product chains and into partnerships where the focus is not on one main company...

  20. Circular threshold quantum secret sharing

    Institute of Scientific and Technical Information of China (English)

    Yang Yu-Guang; Wen Qiao-Yan

    2008-01-01

    This paper proposes a circular threshold quantum secret sharing (TQSS) scheme with polarized single photons.A polarized single photon sequence runs circularly among any t or more of n parties and any t or more of n parties can reconstruct the secret key when they collaborate.It shows that entanglement is not necessary for quantum secret sharing.Moreover,the theoretic efficiency is improved to approach 100% as the single photons carrying the secret key are deterministically forwarded among any t or more of n parties,and each photon can carry one bit of information without quantum storage.This protocol is feasible with current technology.

  1. Neither invented nor shared here

    DEFF Research Database (Denmark)

    Burcharth, Ana Luiza de Araújo; Knudsen, M. P.; Søndergaard, Helle Alsted

    2014-01-01

    against the sourcing of external knowledge (the Not-invented-here (NIH) syndrome) and against the external exploitation of knowledge assets (the Not-shared-here (NSH) syndrome). Using survey data collected from 331 firms, this article empirically assesses the theoretical assertion that the NIH and NSH...

  2. Building a Shared Information Network.

    Science.gov (United States)

    Stanat, Ruth

    1991-01-01

    Discussion of information needs in a business environment focuses on how to build a shared information network. Highlights include the evolution of corporate intelligence systems; results of a survey that examined the information networking needs of large corporations; and a case study of the development of an information network at Citibank N.A.…

  3. Natural deduction : sharing by presentation

    NARCIS (Netherlands)

    Loeb, Iris

    2007-01-01

    Part I of this thesis studies a fragment of natural deduction to which we have added the notion of sharing of subresults. This formalism is called 'deduction graphs'. We show some properties of cut-elimination on deduction graphs, like strong normalisation and confluence. We discuss connections with

  4. Car sharing à la carte

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    Do you want to make your commute to CERN easier, while saving money at the same time? Would you prefer not to spend a quarter of an hour crawling round the CERN car parks looking for a space? If so, read on: this article might well be of great interest to you.   We would like to draw your attention to a well established, albeit sadly under-used, method of transport: car sharing. To promote car-sharing, the GS Department has stepped in to call on the services of the Swiss firm Green Monkeys which specialises in this user-friendly and intelligent transport scheme. The company’s slogan is:  “Car-sharing as you want, when you want and as much as you want”. The principle is very straightforward. To use this car-sharing facility, you simply complete your free online registration with Green Monkeys, providing the following details: your journey, departure time, arrival time and days of the week, and indicating whether you are a passenger or driver or both. &a...

  5. Normal Families and Shared Functions

    Institute of Scientific and Technical Information of China (English)

    WANG Xue-qin; LEI Chun-lin

    2015-01-01

    Let k be a positive integer, let h be a holomorphic function in a domain D, h 6≡0 and let F be a family of nonvanishing meromorphic functions in D. If each pair of functions f and g in F , f (k) and g(k) share h in D, then F is normal in D.

  6. Secret sharing using biometric traits

    Science.gov (United States)

    Kholmatov, Alisher; Yanikoglu, Berrin; Savas, Erkay; Levi, Albert

    2006-04-01

    In biometric based authentication, biometric traits of a person are matched against his/her stored biometric profile and access is granted if there is sufficient match. However, there are other access scenarios, which require participation of multiple previously registered users for a successful authentication or to get an access grant for a certain entity. For instance, there are cryptographic constructs generally known as secret sharing schemes, where a secret is split into shares and distributed amongst participants in such a way that it is reconstructed/revealed only when the necessary number of share holders come together. The revealed secret can then be used for encryption or authentication (if the revealed key is verified against the previously registered value). In this work we propose a method for the biometric based secret sharing. Instead of splitting a secret amongst participants, as is done in cryptography, a single biometric construct is created using the biometric traits of the participants. During authentication, a valid cryptographic key is released out of the construct when the required number of genuine participants present their biometric traits.

  7. Interlibrary Cooperation and Resource Sharing.

    Science.gov (United States)

    Kittel, Dorothy

    Based on fiscal year 1985 annual reports from 48 states, this report describes interlibrary cooperation and resource-sharing activities supported by Library Services and Construction Act (LSCA), Title III, funds during 1985. A summary of types of activities reported includes the establishment, maintenance, and expansion of communication networks…

  8. Moralities of sharing and caring

    NARCIS (Netherlands)

    Niehof, A.; Wahlen, S.

    2017-01-01

    This paper propounds the concept of the moral household economy in order to understand and explain gender performances in food practices of sharing and caring in the socio-cultural domain of unpaid food work. Households are the immediate context for meeting people’s food and nutrition needs and for

  9. Interlibrary Cooperation and Resource Sharing.

    Science.gov (United States)

    Kittel, Dorothy

    Based on fiscal year 1986 annual reports from 48 states, Guam, Puerto Rico, and the Virgin Islands, this report describes interlibrary cooperation and resource sharing activities supported by the Library Services and Construction Act (LSCA), Title III, funds. In response to the 1984 amendment to Title III (which required each state to include in…

  10. Scalable shared-memory multiprocessing

    CERN Document Server

    Lenoski, Daniel E

    1995-01-01

    Dr. Lenoski and Dr. Weber have experience with leading-edge research and practical issues involved in implementing large-scale parallel systems. They were key contributors to the architecture and design of the DASH multiprocessor. Currently, they are involved with commercializing scalable shared-memory technology.

  11. Benefit sharing in health research

    African Journals Online (AJOL)

    2015-08-02

    Aug 2, 2015 ... [4] Those who contribute to scientific research ought to share ... 2 Managing director; Right to Care, Department of Medicine, Clinical HIV Research Unit, Internal Medicine ..... boration with the United Nations and the World Health Organization ... a benefitsharing model that tempers (not diminish) commercial.

  12. Dynamic Spectrum Sharing among Femtocells

    DEFF Research Database (Denmark)

    Da Costa, Gustavo Wagner Oliveira

    2012-01-01

    The ever-growing demand for mobile broadband is leading to an imminent spectrum scarcity. In order to cope with such situation dynamic spectrum sharing and the widespread deployment of small cells (femtocells) are promising solutions. Delivering such a view is not short of challenges. Massive dep...

  13. Moralities of sharing and caring

    NARCIS (Netherlands)

    Niehof, A.; Wahlen, S.

    2017-01-01

    This paper propounds the concept of the moral household economy in order to understand and explain gender performances in food practices of sharing and caring in the socio-cultural domain of unpaid food work. Households are the immediate context for meeting people’s food and nutrition needs and for

  14. Reverse mutation in fragile X syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Antinolo, G.; Borrego, S.; Cabeza, J.C. [Hospital Universitario, Sevilla (Spain)] [and others

    1996-01-01

    The fragile X syndrome is the most common cause of familial mental retardation, with an incidence of {approximately}1/1,500 in males and 1/2,500 in females. The clinical expression includes moderate to severe mental retardation, macroorchidism, dysmorphic facial features and behavior disturbances. In 1991, the FMR-1 gene was isolated from the region of the fragile X site. The fragile X phenotype has been found, in most cases, to be characterized at the molecular level by expansion of a (CGG){sub n} repeat and hypermethylation of a CpG island identified in the 5{prime}-UTR of the FMR-1 gene. It has been proposed, and some evidence has been shown, that germ cells carry only premutation alleles and that expansion occurs at a postzygotic stage. A few cases of reduction of the (CGG){sub n} repeat in fragile X syndrome have been reported. These reductions were from a larger premutation to a smaller premutation, in female-to-male transmission, from full mutation to a mosaic pattern, reduction from mosaic full-mutation/premutation females or regression from premutation to normal. We present here the novel observation of a phenotypically normal female carrying a nonmosaic full-mutation allele in somatic cells who transmits a premutation allele to her daughter. This daughter has three mosaic offspring with the full mutation and the premutation. Two of them are monozygotic (MZ) twins sharing a concordant mutation pattern. They are monoamniotic monochorionic, which indicates a late form of twinning. 20 refs., 1 fig.

  15. Mutational spectrum drives the rise of mutator bacteria.

    Directory of Open Access Journals (Sweden)

    Alejandro Couce

    Full Text Available Understanding how mutator strains emerge in bacterial populations is relevant both to evolutionary theory and to reduce the threat they pose in clinical settings. The rise of mutator alleles is understood as a result of their hitchhiking with linked beneficial mutations, although the factors that govern this process remain unclear. A prominent but underappreciated fact is that each mutator allele increases only a specific spectrum of mutational changes. This spectrum has been speculated to alter the distribution of fitness effects of beneficial mutations, potentially affecting hitchhiking. To study this possibility, we analyzed the fitness distribution of beneficial mutations generated from different mutator and wild-type Escherichia coli strains. Using antibiotic resistance as a model system, we show that mutational spectra can alter these distributions substantially, ultimately determining the competitive ability of each strain across environments. Computer simulation showed that the effect of mutational spectrum on hitchhiking dynamics follows a non-linear function, implying that even slight spectrum-dependent fitness differences are sufficient to alter mutator success frequency by several orders of magnitude. These results indicate an unanticipated central role for the mutational spectrum in the evolution of bacterial mutation rates. At a practical level, this study indicates that knowledge of the molecular details of resistance determinants is crucial for minimizing mutator evolution during antibiotic therapy.

  16. Work-Sharing: Panacea or Palliative?

    Science.gov (United States)

    Dawkins, Peter J.

    1983-01-01

    Recently, high unemployment and a high perceived rate of technological change have created interest in work-sharing. Definitions of different types of work-sharing and theoretical and practical issues related to work-sharing are covered. Work-sharing is not necessarily a panacea, but it does show the potential to help. (Author/IS)

  17. Professional SharePoint 2013 administration

    CERN Document Server

    Young, Shane; Klindt, Todd

    2013-01-01

    SharePoint admin author gurus return to prepare you for working with the new features of SharePoint 2013! The new iteration of SharePoint boasts exciting new features. However, any new version also comes with its fair share of challenges and that's where this book comes in. The team of SharePoint admin gurus returns to presents a fully updated resource that prepares you for making all the new SharePoint 2013 features work right. They cover all of the administration components of SharePoint 2013 in detail, and present a clear understanding of how they affect the role of the adminis

  18. To share or not to share? Business aspects of network sharing for Mobile Network Operators

    NARCIS (Netherlands)

    Berkers, F.T.H.M.; Hendrix, G.; Chatzicharistou, I.; Haas, T. de; Hamera, D.

    2010-01-01

    Radio spectrum and network infrastructure are two essential resources for mobile service delivery, which are both costly and increasingly scarce. In this paper we consider drivers and barriers of network sharing, which is seen as a potential solution for scarcity in these resources. We considered a

  19. Secret sharing scheme with inherited characteristic

    Institute of Scientific and Technical Information of China (English)

    Ye Zhenjun; Meng Fanzhen

    2006-01-01

    To assure the shareholders can look for their "legal" attorneys to renew the secret, once the secret sharing scheme is initialized, a secret sharing scheme with inherited characteristic is constructed. In this scheme, each shareholder can produce a new share by his algorithm, which is equivalent to the primary one. Together with other shares, the primary secret can be renewed. Since this scheme is constructed not by replacing the primary share with a new share produced by the dealer in his primitive secret sharing scheme, so no matter how much shares the shareholder produces, these shares can not be gathered together to renew the secret in this scheme. Compared with the existing secret sharing schemes, this scheme provides more agility for the shareholders by investing each of them a function but not affect its security.

  20. Silting mutation in triangulated categories

    CERN Document Server

    Aihara, Takuma

    2010-01-01

    In representation theory of algebras the notion of `mutation' often plays important roles, and two cases are well known, i.e. `cluster tilting mutation' and `exceptional mutation'. In this paper we focus on `tilting mutation', which has a disadvantage that it is often impossible, i.e. some of summands of a tilting object can not be replaced to get a new tilting object. The aim of this paper is to take away this disadvantage by introducing `silting mutation' for silting objects as a generalization of `tilting mutation'. We shall develope a basic theory of silting mutation. In particular, we introduce a partial order on the set of silting objects and establish the relationship with `silting mutation' by generalizing the theory of Riedmann-Schofield and Happel-Unger. We show that iterated silting mutation act transitively on the set of silting objects for local, hereditary or canonical algebras. Finally we give a bijection between silting subcategories and certain t-structures.

  1. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder. The ...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  2. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  3. Are There Mutator Polymerases?

    Directory of Open Access Journals (Sweden)

    Miguel Garcia-Diaz

    2003-01-01

    Full Text Available DNA polymerases are involved in different cellular events, including genome replication and DNA repair. In the last few years, a large number of novel DNA polymerases have been discovered, and the biochemical analysis of their properties has revealed a long list of intriguing features. Some of these polymerases have a very low fidelity and have been suggested to play mutator roles in different processes, like translesion synthesis or somatic hypermutation. The current view of these processes is reviewed, and the current understanding of DNA polymerases and their role as mutator enzymes is discussed.

  4. GLOBALIZATION IMPACT ON UKRAINIAN MARKET OF SHARES

    Directory of Open Access Journals (Sweden)

    O. Zotsenko

    2013-05-01

    Full Text Available The paper examines the impact of globalization on the Ukrainian market of shares. Main trends of globalization of world share market are analyzed. The study highlights key elements of the operating share markets of the world leading countries. The research investigates main factors that affect on the level of national market of shares. The findings trace out a number of problems that hinder and distort the role of the Ukrainian share market in capital allocation.

  5. Designing for Sharing in Local Communities

    DEFF Research Database (Denmark)

    Malmborg, Lone; Light, Ann; Fitzpatrick, Geraldine

    2015-01-01

    The Sharing Economy has brought new attention to the everyday practice of sharing. Digital tools are changing both what we can do together across neighbourhoods and how we think about sharing our time, materials and skills. It is possible to design to boost resource management, economic wellbeing...... and social resilience by fostering sharing practices, but do different designs speak to different priorities in design for sharing?...

  6. Shared energy savings (SES) contracting

    Energy Technology Data Exchange (ETDEWEB)

    Aldridge, D.R. Jr. [Army Corps of Engineers, Huntsville, AL (United States)

    1995-11-01

    This paper discusses the use of a Shared Energy Savings (SES) contract as the procurement vehicle to provide, install, and maintain closed-loop ground-coupled heat pumps (CLGCHP`s) for 4,003 family-housing units at Fort Polk, Louisiana. In addition to the requirement relative to heat pumps, the contract allows the energy service company (ESCO) to propose additional projects needed to take full advantage of energy cost-saving opportunities that may exist at Fort Polk. The paper traces the development of the SES contract from feasibility study through development of the request for proposal (RFP) to contract award and implementation. In tracing this development, technical aspects of the project are set forth and various benefits inherent in SES contracting are indicated. The paper concludes that, due to the positive motivation inherent in the shared-savings, as well as partnering aspects of SES contracts, SES contracting is well suited to use as a procurement vehicle.

  7. Barriers to Cyber Information Sharing

    Science.gov (United States)

    2014-12-01

    initial areas; telecommunications, energy, banking and finance, transportation , water systems and emergency services, both government and private. PDD 63...protection/how-retailers-can- boost-security-through-information-sharing.html. 183 Lech Janczewski and Andrew M. Colarik, Cyber Warfare and Cyber...iSight Partners. 2014. What Is Cyber Threat Intelligence and Why Do I Need It? Dallas: iSIGHT Partners, 2014. Janczewski, Lech and Andrew M

  8. So This is Knowledge Sharing

    Science.gov (United States)

    Motil, Susan

    2003-01-01

    People within large organizations have probably already dealt with problems similar to the problems that you face; you can save time and money by taking advantage of that experience and knowledge. Knowledge sharing by mentors can empower less experienced managers who would otherwise not challenge the status quo. Reviews should encourage joint problem solving rather than just reporting. To accomplish this, ensure that the review process is viewed as feedback from independent and supportive experts.

  9. The evolution of reciprocal sharing

    OpenAIRE

    Moore, Jim

    1984-01-01

    Genetical models of the evolution of reciprocal altruism (as distinct from cooperation, mutualism, or nepotism) have difficulty explaining the initial establishment of an altruist gene in a selfish deme. Though potential mechanisms have been suggested, there is an alternative: much "altruistic" behavior may in fact be purely selfish in origin and consequently reciprocity need not be invoked to provide a selective benefit to the actor. _Sharing_ and _helping_ are fundamentally different behavi...

  10. Population genetics and benefit sharing.

    Science.gov (United States)

    Knoppers, B M

    2000-01-01

    The majority of international or national guidelines, specific to human genetics concentrate on actual or potential clinical applications. In contrast, the Ethics Committee of the Human Genome Organisation (HUGO) attempts to provide guidance to the bench scientists engaged in fundamental research in genomics prior to any clinical applications. Often confused as constituting the Human Genome Project (HGP) itself, HUGO's (Human Genome Organization) ultimate goal is to assist in the worldwide collaboration underpinning the HGP. It is an international organisation with 1,229 members in approximately 60 countries. The Ethics Committee is one of HUGO's six international advisory committees. Composed of experts from a number of countries and disciplines, the HUGO Ethics Committee promotes discussion and understanding of social, legal, and ethical issues as they relate to the conduct of, and knowledge derived from, the Genome Initiative. Currently, it has 13 members from 11 difference countries. It has produced statements on the conduct of genetic research, on cloning, and, has most recently presented a 'Statement on Benefit-Sharing', April 11, 2000. The Intellectual Property Committee of HUGO has been active in the controversial area of patenting. The issue of benefit-sharing is one that has its source in the mandate of both committees. How to avoid both commodification of the person through payment for access to DNA and biopiracy with no return to benefits to the families or community? While patents are a legitimate form of recognition for innovation, there seems to be no therapeutic exception to some of its stringent rules and the 'morality' exclusion has lain dormant. The HUGO 'Statement on Benefit-Sharing' examines the issues of defining community, common heritage, distributive justice and solidarity before arriving at its conclusions in benefit-sharing. This communication reviews some of these issues.

  11. Hadron therapy information sharing prototype

    OpenAIRE

    Roman, Faustin Laurentiu; Abler, Daniel; Kanellopoulos, Vassiliki; Amorós Vicente, Gabriel; Davies, Jim; Dosanjh, Manjit; Jena, Raj; Kirkby, Norman; Peach, Ken; Salt Cairols, José

    2013-01-01

    The European PARTNER project developed a prototypical system for sharing hadron therapy data. This system allows doctors and patients to record and report treatment-related events during and after hadron therapy. It presents doctors and statisticians with an integrated view of adverse events across institutions, using open-source components for data federation, semantics, and analysis. There is a particular emphasis upon semantic consistency, achieved through intelligent, annotated form desig...

  12. RACE pulls for shared control

    Science.gov (United States)

    Leahy, M. B., Jr.; Cassiday, B. K.

    1993-02-01

    Maintaining and supporting an aircraft fleet, in a climate of reduced manpower and financial resources, dictates effective utilization of robotics and automation technologies. To help develop a winning robotics and automation program the Air Force Logistics Command created the Robotics and Automation Center of Excellence (RACE). RACE is a command wide focal point. Race is an organic source of expertise to assist the Air Logistic Center (ALC) product directorates in improving process productivity through the judicious insertion of robotics and automation technologies. RACE is a champion for pulling emerging technologies into the aircraft logistic centers. One of those technology pulls is shared control. Small batch sizes, feature uncertainty, and varying work load conspire to make classic industrial robotic solutions impractical. One can view ALC process problems in the context of space robotics without the time delay. The ALC's will benefit greatly from the implementation of a common architecture that supports a range of control actions from fully autonomous to teleoperated. Working with national laboratories and private industry, we hope to transition shared control technology to the depot floor. This paper provides an overview of the RACE internal initiatives and customer support, with particular emphasis on production processes that will benefit from shared control technology.

  13. Plant Breeding by Using Radiation Mutation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Si Yong; Kim, Dong Sub; Lee, Geung Joo (and others)

    2007-06-15

    A mutation breeding is to use physical or chemical mutagens to induce mutagenesis, followed by individual selections with favorable traits. The mutation breeding has many advantages over other breeding methods, which include the usefulness for improving one or two inferior characteristics, applications to broad species with different reproductive systems or to diverse plant materials, native or plant introduction with narrow genetic background, time and cost-effectiveness, and valuable mutant resources for genomic researches. Recent applications of the radiation breeding techniques to developments of flowering plants or food crops with improved functional constituents heightened the public's interests in agriculture and in our genetic resources and seed industries. The goals of this project, therefore, include achieving advances in domestic seed industries and agricultural productivities by developing and using new radiation mutants with favored traits, protecting an intellectual property right of domestic seeds or germplasm, and sharing the valuable mutants and mutated gene information for the genomic and biotech researches that eventually leads to economic benefits.

  14. Msx1 Mutations

    Science.gov (United States)

    Wang, Y.; Kong, H.; Mues, G.; D’Souza, R.

    2011-01-01

    Mutations in the transcription factors PAX9 and MSX1 cause selective tooth agenesis in humans. In tooth bud mesenchyme of mice, both proteins are required for the expression of Bmp4, which is the key signaling factor for progression to the next step of tooth development. We have previously shown that Pax9 can transactivate a 2.4-kb Bmp4 promoter construct, and that most tooth-agenesis-causing PAX9 mutations impair DNA binding and Bmp4 promoter activation. We also found that Msx1 by itself represses transcription from this proximal Bmp4 promoter, and that, in combination with Pax9, it acts as a potentiator of Pax9-induced Bmp4 transactivation. This synergism of Msx1 with Pax9 is significant, because it is currently the only documented mechanism for Msx1-mediated activation of Bmp4. In this study, we investigated whether the 5 known tooth-agenesis-causing MSX1 missense mutations disrupt this Pax9-potentiation effect, or if they lead to deficiencies in protein stability, protein-protein interactions, nuclear translocation, and DNA-binding. We found that none of the studied molecular mechanisms yielded a satisfactory explanation for the pathogenic effects of the Msx1 mutations, calling for an entirely different approach to the investigation of this step of odontogenesis on the molecular level. PMID:21297014

  15. Hypertrophy, fibrosis, and sudden cardiac death in response to pathological stimuli in mice with mutations in cardiac troponin T

    NARCIS (Netherlands)

    Maass, AH; Ikeda, K; Oberdorf-Maass, S; Maier, SKG; Leinwand, LA

    2004-01-01

    Background-Transgenic mouse models expressing a missense mutation (R92Q) or a splice donor site mutation (trunc) in the cardiac troponin T (cTnT) model familial hypertrophic cardiomyopathy (FHC) in humans. Although males from these strains share the unusual property of having significantly smaller v

  16. Genetic uptake in BRCA-mutation families is related to emotional and behavioral communication characteristics of index patients.

    NARCIS (Netherlands)

    Landsbergen, K.M.; Verhaak, C.M.; Kraaimaat, F.W.; Hoogerbrugge-van der Linden, N.

    2005-01-01

    INTRODUCTION: Carriers of a hereditary mutation in BRCA are at high risk for breast and ovarian cancer. The first person from a family known to carry the mutation, the index person, has to share genetic information with relatives. This study is aimed at determining the number of relatives tested for

  17. Exome sequencing reveals AMER1 as a frequently mutated gene in colorectal cancer

    Science.gov (United States)

    Sanz-Pamplona, Rebeca; Lopez-Doriga, Adriana; Paré-Brunet, Laia; Lázaro, Kira; Bellido, Fernando; Alonso, M. Henar; Aussó, Susanna; Guinó, Elisabet; Beltrán, Sergi; Castro-Giner, Francesc; Gut, Marta; Sanjuan, Xavier; Closa, Adria; Cordero, David; Morón-Duran, Francisco D.; Soriano, Antonio; Salazar, Ramón; Valle, Laura; Moreno, Victor

    2015-01-01

    PURPOSE Somatic mutations occur at early stages of adenoma and accumulate throughout colorectal cancer (CRC) progression. The aim of this study was to characterize the mutational landscape of stage II tumors and to search for novel recurrent mutations likely implicated in CRC tumorigenesis. DESIGN The exomic DNA of 42 stage II, microsatellite stable, colon tumors and their paired mucosae were sequenced. Other molecular data available in the discovery dataset (gene expression, methylation, and CNV) was used to further characterize these tumors. Additional datasets comprising 553 CRC samples were used to validate the discovered mutations. RESULTS As a result, 4,886 somatic single nucleotide variants (SNVs) were found. Almost all SNVs were private changes, with few mutations shared by more than one tumor, thus revealing tumor-specific mutational landscapes. Nevertheless, these diverse mutations converged into common cellular pathways such as cell cycle or apoptosis. Among this mutational heterogeneity, variants resulting in early stop-codons in the AMER1 (also known as FAM123B or WTX) gene emerged as recurrent mutations in CRC. Loses of AMER1 by other mechanisms apart from mutations such as methylation and copy number aberrations were also found. Tumors lacking this tumor suppressor gene exhibited a mesenchymal phenotype characterized by inhibition of the canonical Wnt pathway. CONCLUSION In silico and experimental validation in independent datasets confirmed the existence of functional mutations in AMER1 in approximately 10% of analyzed CRC tumors. Moreover, these tumors exhibited a characteristic phenotype. PMID:26071483

  18. Mutations in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Reichardt, J.K.V. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States)

    1995-10-01

    This Letter raises four issues concerning two papers on galactosemia published in the March 1995 of the Journal. First, table 2 in the paper by Elsas et al. incorrectly attributes seven galactose-l-phosphate uridyl transferase (GALT) mutations (S135L, L195P, K285N, N314D, R333W, R333G, and K334R). The table also fails to mention that others have reported the same two findings attributed to {open_quotes}Leslie et al.; Elsas et al. and in press{close_quotes} and {open_quotes}Leslie et al.; Elsas et al.{close_quotes} The first finding on the prevalence of the Q188R galactosemia mutation in the G/G Caucasian population has also been described by Ng et al., and the second finding on the correlation of the N314D GALT mutation with the Duarte variant was reported by Lin et al. Second, Elsas et al. suggest that the E203K and N314D mutations may {open_quotes}produce intra-allelic complementation when in cis{close_quotes}. This speculation is supported by the activity data of individual III-2 but is inconsistent with the activities of three other individuals I-1, II-1, and III-1 of the same pedigree. The GALT activity measured in these three individuals suggests a dominant negative effect of E203K in E203K-N314D chromosomes, since they all have less than normal activity. Thus, the preponderance of the data in this paper is at odds with the authors speculation. It is worth recalling that Lin et al. also identified four N314D GALT mutations on 95 galactosemic chromosomes examined. A similar situation also appears to be the case in proband III-1 (with genotype E203K-N314D/IVSC) in the Elsas et al. paper. 9 refs.

  19. Evolutionary Stability Against Multiple Mutations

    CERN Document Server

    Ghatak, Anirban; Shaiju, A J

    2012-01-01

    It is known (see e.g. Weibull (1995)) that ESS is not robust against multiple mutations. In this article, we introduce robustness against multiple mutations and study some equivalent formulations and consequences.

  20. BRAF mutations in conjunctival melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahl, Christina; Dahmcke, Christina M.

    2016-01-01

    Purpose: To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection. Methods: Data from 139 patients...

  1. Understanding shared services (Article 1 of 3

    Directory of Open Access Journals (Sweden)

    T. N. Van der Linde

    2006-12-01

    Full Text Available Purpose: Shared services is a viable business model that can be used by organisations to reduce costs and enhance efficiency and effectiveness in the organisation. The purpose of this trilogy of articles is to introduce shared services as a business model, and how to efficiently and effectively manage a shared services business unit. The purpose of the first article in the trilogy, introduces shared services as a business model, defines what shared services is, the transformation required to successfully implement a shared services business model, as well as the benefits that can be derived from implementing a shared services business model. Methodology: A comprehensive literature study was conducted in order to: - Define and describe shared services as a business model, - Compare shared services with centralisation and de-centralisation, - Determine and describe the transformation required to successfully implement shared services. Findings: In the article, a framework is generated to help organisations understand the business concept of shared services. This work has further potential: when applied correctly, there are both tangible and intangible benefits that can be accrued above cost savings. Implications: The findings of this article are important for organisations that are in the process of implementing or have implemented shared services, as it will assist the organisation in determining if shared services is the correct business model for them to implement. Value: This article provides an understanding of shared services and the business environment required to successfully implement a shared services business model. Value created by a shared services business model is further enhanced once the organisation has embarked on the successful implementation of a shared services business model, which is the primary objective of the second article, Implementation and continuous evolution in shared services.

  2. SharePoint 2010 For Dummies

    CERN Document Server

    Williams, Vanessa L

    2012-01-01

    Here's the bestselling guide on SharePoint 2010, updated to cover Office 365 SharePoint Portal Server is an essential part of the enterprise infrastructure for many businesses. The Office 365 version includes significantly enhanced cloud capabilities. This second edition of the bestselling guide to SharePoint covers getting a SharePoint site up and running, branded, populated with content, and more. It explains ongoing site management and offers plenty of advice for administrators who want to leverage SharePoint and Office 365 in various ways.Many businesses today rely on SharePoint Portal Ser

  3. Professional SharePoint 2010 Development

    CERN Document Server

    Rizzo, Tom; Fried, Jeff; Swider, Paul J; Hillier, Scot; Schaefer, Kenneth

    2012-01-01

    Updated guidance on how to take advantage of the newest features of SharePoint programmability More than simply a portal, SharePoint is Microsoft's popular content management solution for building intranets and websites or hosting wikis and blogs. Offering broad coverage on all aspects of development for the SharePoint platform, this comprehensive book shows you exactly what SharePoint does, how to build solutions, and what features are accessible within SharePoint. Written by a team of SharePoint experts, this new edition offers an extensive selection of field-tested best practices that shows

  4. Professional SharePoint 2013 development

    CERN Document Server

    Alirezaei, Reza; Ranlett, Matt; Hillier, Scot; Wilson, Brian; Fried, Jeff; Swider, Paul

    2013-01-01

    Thorough coverage of development in SharePoint 2013 A team of well-known Microsoft MVPs joins forces in this fully updated resource, providing you with in-depth coverage of development tools in the latest iteration of the immensely popular SharePoint. From building solutions to building custom workflow and content management applications, this book shares field-tested best practices on all aspect of SharePoint 2013 development. Offers a thorough look at Windows Azure and SharePoint 2013Includes new chapters on Application Life Cycle Management, developing apps in ShareP

  5. SharePoint 2010 Field Guide

    CERN Document Server

    Mann, Steven; Gazmuri, Pablo; Caravajal, Steve; Wheeler, Christina

    2012-01-01

    Hands-on solutions for common SharePoint 2010 challenges Aimed at the more than 100 million licensed SharePoint 2010 users, this indispensable field guide addresses an abundance of common SharePoint 2010 problems and offers proven solutions. A team of authors encourages you to customize SharePoint beyond the out-of-the-box functionality so that you can build more complex solutions to these challenges. You?ll discover intricate details and specific full-scale solutions that you can then implement to your own SharePoint 2010 solutions.Tackles a variety of SharePoint 2010 problems ranging from si

  6. Mutational analysis of primary central nervous system lymphoma.

    Science.gov (United States)

    Bruno, Aurélie; Boisselier, Blandine; Labreche, Karim; Marie, Yannick; Polivka, Marc; Jouvet, Anne; Adam, Clovis; Figarella-Branger, Dominique; Miquel, Catherine; Eimer, Sandrine; Houillier, Caroline; Soussain, Carole; Mokhtari, Karima; Daveau, Romain; Hoang-Xuan, Khê

    2014-07-15

    Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.

  7. Better living with hyper-mutation.

    Science.gov (United States)

    Goodman, Myron F

    2016-07-01

    The simplest forms of mutations, base substitutions, typically have negative consequences, aside from their existential role in evolution and fitness. Hypermutations, mutations on steroids, occurring at frequencies of 10(-2) -10(-4) per base pair, straddle a domain between fitness and death, depending on the presence or absence of regulatory constraints. Two facets of hypermutation, one in Escherichia coli involving DNA polymerase V (pol V), the other in humans, involving activation-induced deoxycytidine deaminase (AID) are portrayed. Pol V is induced as part of the DNA-damage-induced SOS regulon, and is responsible for generating the lion's share of mutations when catalyzing translesion DNA synthesis (TLS). Four regulatory mechanisms, temporal, internal, conformational, and spatial, activate pol V to copy damaged DNA and then deactivate it. On the flip side of the coin, SOS-induced pols V, IV, and II mutate undamaged DNA, thus providing genetic diversity heightening long-term survival and evolutionary fitness. Fitness in humans is principally the domain of a remarkably versatile immune system marked by somatic hypermutations (SHM) in immunoglobulin variable (IgV) regions that ensure antibody (Ab) diversity. AID initiates SHM by deaminating C → U, favoring hot WRC (W = A/T, R = A/G) motifs. Since there are large numbers of trinucleotide motif targets throughout IgV, AID must exercise considerable catalytic restraint to avoid attacking such sites repeatedly, which would otherwise compromise diversity. Processive, random, and inefficient AID-catalyzed dC deamination simulates salient features of SHM, yet generates B-cell lymphomas when working at the wrong time in the wrong place. Environ. Mol. Mutagen. 57:421-434, 2016. © 2016 Wiley Periodicals, Inc.

  8. ELOVL5 Mutations Cause Spinocerebellar Ataxia 38

    Science.gov (United States)

    Di Gregorio, Eleonora; Borroni, Barbara; Giorgio, Elisa; Lacerenza, Daniela; Ferrero, Marta; Lo Buono, Nicola; Ragusa, Neftj; Mancini, Cecilia; Gaussen, Marion; Calcia, Alessandro; Mitro, Nico; Hoxha, Eriola; Mura, Isabella; Coviello, Domenico A.; Moon, Young-Ah; Tesson, Christelle; Vaula, Giovanna; Couarch, Philippe; Orsi, Laura; Duregon, Eleonora; Papotti, Mauro Giulio; Deleuze, Jean-François; Imbert, Jean; Costanzi, Chiara; Padovani, Alessandro; Giunti, Paola; Maillet-Vioud, Marcel; Durr, Alexandra; Brice, Alexis; Tempia, Filippo; Funaro, Ada; Boccone, Loredana; Caruso, Donatella; Stevanin, Giovanni; Brusco, Alfredo

    2014-01-01

    Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases. PMID:25065913

  9. ELOVL5 mutations cause spinocerebellar ataxia 38.

    Science.gov (United States)

    Di Gregorio, Eleonora; Borroni, Barbara; Giorgio, Elisa; Lacerenza, Daniela; Ferrero, Marta; Lo Buono, Nicola; Ragusa, Neftj; Mancini, Cecilia; Gaussen, Marion; Calcia, Alessandro; Mitro, Nico; Hoxha, Eriola; Mura, Isabella; Coviello, Domenico A; Moon, Young-Ah; Tesson, Christelle; Vaula, Giovanna; Couarch, Philippe; Orsi, Laura; Duregon, Eleonora; Papotti, Mauro Giulio; Deleuze, Jean-François; Imbert, Jean; Costanzi, Chiara; Padovani, Alessandro; Giunti, Paola; Maillet-Vioud, Marcel; Durr, Alexandra; Brice, Alexis; Tempia, Filippo; Funaro, Ada; Boccone, Loredana; Caruso, Donatella; Stevanin, Giovanni; Brusco, Alfredo

    2014-08-07

    Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal-dominant neurodegenerative disorders involving the cerebellum and 23 different genes. We mapped SCA38 to a 56 Mb region on chromosome 6p in a SCA-affected Italian family by whole-genome linkage analysis. Targeted resequencing identified a single missense mutation (c.689G>T [p.Gly230Val]) in ELOVL5. Mutation screening of 456 independent SCA-affected individuals identified the same mutation in two further unrelated Italian families. Haplotyping showed that at least two of the three families shared a common ancestor. One further missense variant (c.214C>G [p.Leu72Val]) was found in a French family. Both missense changes affect conserved amino acids, are predicted to be damaging by multiple bioinformatics tools, and were not identified in ethnically matched controls or within variant databases. ELOVL5 encodes an elongase involved in the synthesis of polyunsaturated fatty acids of the ω3 and ω6 series. Arachidonic acid and docosahexaenoic acid, two final products of the enzyme, were reduced in the serum of affected individuals. Immunohistochemistry on control mice and human brain demonstrated high levels in Purkinje cells. In transfection experiments, subcellular localization of altered ELOVL5 showed a perinuclear distribution with a signal increase in the Golgi compartment, whereas the wild-type showed a widespread signal in the endoplasmic reticulum. SCA38 and SCA34 are examples of SCAs due to mutations in elongase-encoding genes, emphasizing the importance of fatty-acid metabolism in neurological diseases.

  10. Employee share ownership in Germany

    DEFF Research Database (Denmark)

    Ortlieb, Renate; Matiaske, Wenzel; Fietze, Simon

    2016-01-01

    on an institutional theoretical framework, this article examines what aims firms pursue through the provision of ESO. The data originate from a survey of firms in Germany. The cluster analytic findings indicate distinctive patterns of relationships between aims and firm characteristics. Aims related to employee...... performance are most important to foreign-owned firms, financial aims are most important to non-public small and medium-sized firms and aims related to corporate image are most important to big firms and to firms that do not provide profit sharing. Aims related to employee attraction and retention are almost...

  11. Organisational Diversity and Knowledge Sharing

    DEFF Research Database (Denmark)

    Lauring, Jakob; Jonasson, Charlotte

    segments. But a substantial critique has recently been launched at the arguments for the business case for diversity, especially in the employment of knowledge synergies. Most studies that support or reject the business case argument have limited their research to establish a link between organisational...... productivity and diversity management - that is not engaging in a discussion of how and why there could be potential benefits or difficulties. In this paper we will describe and analyse some of the complications multicultural organisations can experience in regard to knowledge sharing...

  12. Analysing lawyers’ attitude towards knowledge sharing

    Directory of Open Access Journals (Sweden)

    Wole M. Olatokun

    2012-02-01

    Full Text Available Objectives: The study examined and identified the factors that affect lawyers’ attitudes to knowledge sharing, and their knowledge sharing behaviour. Specifically, it investigated the relationship between the salient beliefs affecting the knowledge sharing attitude of lawyers’, and applied a modified version of the Theory of Reasoned Action (TRA in the knowledge sharing context, to predict how these factors affect their knowledge sharing behaviour.Method: A field survey of 273 lawyers was carried out, using questionnaire for data collection. Collected data on all variables were structured into grouped frequency distributions. Principal Component Factor Analysis was applied to reduce the constructs and Simple Regression was applied to test the hypotheses. These were tested at 0.05% level of significance.Results: Results showed that expected associations and contributions were the major determinants of lawyers’ attitudes towards knowledge sharing. Expected reward was not significantly related to lawyers’ attitudes towards knowledge sharing. A positive attitude towards knowledge sharing was found to lead to a positive intention to share knowledge, although a positive intention to share knowledge did not significantly predict a positive knowledge sharing behaviour. The level of Information Technology (IT usage was also found to significantly affect the knowledge sharing behaviour of lawyers’.Conclusion: It was recommended that law firms in the study area should deploy more IT infrastructure and services that encourage effective knowledge sharing amongst lawyers. 

  13. To share or not to share : Parental, sibling, and situational influences on sharing with a younger sibling

    NARCIS (Netherlands)

    Van Berkel, Sheila R.; Van Der Pol, Lotte D.; Groeneveld, Marleen G.; Hallers-Haalboom, Elizabeth T.; Endendijk, Joyce J.; Mesman, Judi; Bakermans-Kranenburg, Marian J.

    2015-01-01

    Sharing is an important indicator of internalised prosocial values. We examined predictors of sharing of 302 preschoolers with their younger siblings in a one-year longitudinal study. Sharing was observed during different home visits, once with father and once with mother. We examined the following

  14. To share or not to share, that is the question. Conditions for the willingness to share knowledge

    NARCIS (Netherlands)

    Andriessen, J.H.E.

    2006-01-01

    Sharing knowledge is an important aspect of most modern organisation. Ideas about how to stimulate knowledge sharing abound, but without much theorising. The objective of this article is to link basic motivation theories to empirical studies of knowledge sharing and its conditions. The paper starts

  15. PINK1: a critical protein kinase in the molecular mechanisms involved in Cancer and Parkinson's disease

    OpenAIRE

    Jiménez Sainz, Judit

    2012-01-01

    El cáncer y la enfermedad de Parkinson (PD) son dos enfermedades en las que el mecanismo pato- fisiológico final no está completamente definido. Datos epidemiológicos indican que los pacientes con PD poseen bajo riesgo de cáncer, con la excepción de melanoma maligno y cánceres de piel, tiroides y mama, lo que sugiere una conexión funcional entre PD y cáncer. Apoyando esta conexión, la desregulación de la homeostasis mitocondrial es una característica importante en la patogénesis de ambas ...

  16. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery

    OpenAIRE

    Yang, Yufeng; Ouyang, Yingshi; Yang, Lichuan; Beal, M. Flint; McQuibban, Angus; Vogel, Hannes; Lu, Bingwei

    2008-01-01

    Mitochondria form dynamic tubular networks that undergo frequent morphological changes through fission and fusion, the imbalance of which can affect cell survival in general and impact synaptic transmission and plasticity in neurons in particular. Some core components of the mitochondrial fission/fusion machinery, including the dynamin-like GTPases Drp1, Mitofusin, Opa1, and the Drp1-interacting protein Fis1, have been identified. How the fission and fusion processes are regulated under norma...

  17. Kin Selection - Mutation Balance

    DEFF Research Database (Denmark)

    Dyken, J. David Van; Linksvayer, Timothy Arnold; Wade, Michael J.

    2011-01-01

    Abstract Social conflict, in the form of intraspecific selfish "cheating" has been observed in a number of natural systems. However, a formal, evolutionary genetic theory of social cheating that provides an explanatory, predictive framework for these observations is lacking. Here we derive the kin...... selection-mutation balance, which provides an evolutionary null hypothesis for the statics and dynamics of cheating. When social interactions have linear fitness effects and Hamilton´s rule is satisfied, selection is never strong enough to eliminate recurrent cheater mutants from a population, but cheater...... lineages are transient and do not invade. Instead, cheating lineages are eliminated by kin selection but are constantly reintroduced by mutation, maintaining a stable equilibrium frequency of cheaters. The presence of cheaters at equilibrium creates a "cheater load" that selects for mechanisms of cheater...

  18. Indirect Medical Education and Disproportionate Share Adj...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Indirect Medical Education and Disproportionate Share Adjustments to Medicare Inpatient Payment Rates The indirect medical education (IME) and disproportionate share...

  19. Shopping for a Time-sharing Service

    Science.gov (United States)

    Elkholy, Hussein

    1970-01-01

    Offers the potential user of digital computers information and suggestions for acquiring a time-sharing system. The results of a survey of the equipment, cost, and services offered by a sample of time-sharing firms are presented. (LC)

  20. Ethics in Data Sharing (Dagstuhl Seminar 14052)

    OpenAIRE

    Cohen, Julie E.; Dietrich, Sven; Pras, Aiko; Zuck, Lenore D.; Hildebrand Mireille

    2014-01-01

    This report documents the program and the outcomes of Dagstuhl Seminar 14052 "Ethics in Data Sharing". The seminar brought together computer scientists, an ethicist and legal scholars to discuss the topic of "ethics in data sharing."

  1. Private Sharing of IOCs and Sightings

    NARCIS (Netherlands)

    Kamp, van de Tim; Peter, Andreas; Everts, Maarten H.; Jonker, Willem

    2016-01-01

    Information sharing helps to better protect computer systems against digital threats and known attacks. However, since security information is usually considered sensitive, parties are hesitant to share all their information through public channels. Instead, they only exchange this information with

  2. Image Sharing in Radiology-A Primer.

    Science.gov (United States)

    Chatterjee, Arindam R; Stalcup, Seth; Sharma, Arjun; Sato, T Shawn; Gupta, Pushpender; Lee, Yueh Z; Malone, Christopher; McBee, Morgan; Hotaling, Elise L; Kansagra, Akash P

    2017-03-01

    By virtue of its information technology-oriented infrastructure, the specialty of radiology is uniquely positioned to be at the forefront of efforts to promote data sharing across the healthcare enterprise, including particularly image sharing. The potential benefits of image sharing for clinical, research, and educational applications in radiology are immense. In this work, our group-the Association of University Radiologists (AUR) Radiology Research Alliance Task Force on Image Sharing-reviews the benefits of implementing image sharing capability, introduces current image sharing platforms and details their unique requirements, and presents emerging platforms that may see greater adoption in the future. By understanding this complex ecosystem of image sharing solutions, radiologists can become important advocates for the successful implementation of these powerful image sharing resources.

  3. Shopping for a Time-sharing Service

    Science.gov (United States)

    Elkholy, Hussein

    1970-01-01

    Offers the potential user of digital computers information and suggestions for acquiring a time-sharing system. The results of a survey of the equipment, cost, and services offered by a sample of time-sharing firms are presented. (LC)

  4. Indirect Medical Education and Disproportionate Share Adj...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Indirect Medical Education and Disproportionate Share Adjustments to Medicare Inpatient Payment Rates The indirect medical education (IME) and disproportionate share...

  5. Mutation of Auslander generators

    CERN Document Server

    Lada, Magdalini

    2009-01-01

    Let $\\Lambda$ be an artin algebra with representation dimension equal to three and $M$ an Auslander generator of $\\Lambda$. We show how, under certain assumptions, we can mutate $M$ to get a new Auslander generator whose endomorphism ring is derived equivalent to the endomorphism ring of $M$. We apply our results to selfinjective algebras with radical cube zero of infinite representation type, where we construct an infinite set of Auslander generators.

  6. Sex and deleterious mutations.

    Science.gov (United States)

    Gordo, Isabel; Campos, Paulo R A

    2008-05-01

    The evolutionary advantage of sexual reproduction has been considered as one of the most pressing questions in evolutionary biology. While a pluralistic view of the evolution of sex and recombination has been suggested by some, here we take a simpler view and try to quantify the conditions under which sex can evolve given a set of minimal assumptions. Since real populations are finite and also subject to recurrent deleterious mutations, this minimal model should apply generally to all populations. We show that the maximum advantage of recombination occurs for an intermediate value of the deleterious effect of mutations. Furthermore we show that the conditions under which the biggest advantage of sex is achieved are those that produce the fastest fitness decline in the corresponding asexual population and are therefore the conditions for which Muller's ratchet has the strongest effect. We also show that the selective advantage of a modifier of the recombination rate depends on its strength. The quantification of the range of selective effects that favors recombination then leads us to suggest that, if in stressful environments the effect of deleterious mutations is enhanced, a connection between sex and stress could be expected, as it is found in several species.

  7. Septin mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Elias T Spiliotis

    2016-11-01

    Full Text Available Septins are GTP-binding proteins that are evolutionarily and structurally related to the RAS oncogenes. Septin expression levels are altered in many cancers and new advances point to how abnormal septin expression may contribute to the progression of cancer. In contrast to the RAS GTPases, which are frequently mutated and actively promote tumorigenesis, little is known about the occurrence and role of septin mutations in human cancers. Here, we review septin missense mutations that are currently in the Catalog of Somatic Mutations in Cancer (COSMIC database. The majority of septin mutations occur in tumors of the large intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in SEPT2, SEPT4 and SEPT9 belong to large intestine tumors. From all septins, SEPT9 and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large intestine cancers. While septin mutations occur with frequencies lower than 3%, recurring mutations in several invariant and highly conserved amino acids are found across different septin paralogs and tumor types. Interestingly, a significant number of these mutations occur in the GTP-binding pocket and septin dimerization interfaces. Future studies may determine how these somatic mutations affect septin structure and function, whether they contribute to the progression of specific cancers and if they could serve as tumor-specific biomarkers.

  8. Team learning: building shared mental models

    NARCIS (Netherlands)

    Bossche, van den P.; Gijselaers, W.; Segers, M.; Woltjer, G.B.; Kirschner, P.

    2011-01-01

    To gain insight in the social processes that underlie knowledge sharing in teams, this article questions which team learning behaviors lead to the construction of a shared mental model. Additionally, it explores how the development of shared mental models mediates the relation between team learning

  9. Team Learning: Building Shared Mental Models

    Science.gov (United States)

    Van den Bossche, Piet; Gijselaers, Wim; Segers, Mien; Woltjer, Geert; Kirschner, Paul

    2011-01-01

    To gain insight in the social processes that underlie knowledge sharing in teams, this article questions which team learning behaviors lead to the construction of a shared mental model. Additionally, it explores how the development of shared mental models mediates the relation between team learning behaviors and team effectiveness. Analyses were…

  10. 47 CFR 73.1715 - Share time.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Share time. 73.1715 Section 73.1715... Rules Applicable to All Broadcast Stations § 73.1715 Share time. Operation is permitted by two or more... considered part of their licenses. (a) If the licenses of stations authorized to share time do not...

  11. Team learning: building shared mental models

    NARCIS (Netherlands)

    Bossche, van den P.; Gijselaers, W.; Segers, M.; Woltjer, G.B.; Kirschner, P.

    2011-01-01

    To gain insight in the social processes that underlie knowledge sharing in teams, this article questions which team learning behaviors lead to the construction of a shared mental model. Additionally, it explores how the development of shared mental models mediates the relation between team learning

  12. 38 CFR 17.274 - Cost sharing.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Cost sharing. 17.274 Section 17.274 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Civilian... the beneficiary cost share. (b) In addition to the beneficiary cost share, an annual (calendar...

  13. Fair Shares, Matey, or Walk the Plank

    Science.gov (United States)

    Wilson, P. Holt; Myers, Marrielle; Edgington, Cyndi; Confrey, Jere

    2012-01-01

    Whether sharing a collection of toys among friends or a pie for dessert, children as young as kindergarten age are keen on making sure that everyone gets their "fair share." In the classroom, fair-sharing activities call for creating equal-size groups from a collection of objects or creating equal-size parts of a whole and are generally used by…

  14. Nash Equilibria in Shared Effort Games

    NARCIS (Netherlands)

    Polevoy, G.; Trajanovski, S.; De Weerdt, M.M.

    2014-01-01

    Shared effort games model people's contribution to projects and sharing the obtained profits. Those games generalize both public projects like writing for Wikipedia, where everybody shares the resulting benefits, and all-pay auctions such as contests and political campaigns, where only the winner ob

  15. SharePoint Office Pocket Guide

    CERN Document Server

    Webb, Jeff

    2009-01-01

    With this handy reference as your guide, you can reap all the benefits of SharePoint--Microsoft's amazing information-sharing tool. It shows you, in plain language, how to construct a web site where individuals from all over can capture and share ideas. Learn how to upload documents, edit content, send alerts, track work items, add new team members, and much more.

  16. Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.

    Science.gov (United States)

    Wang, Zheng; Zhang, Weimin; Wang, Yun; Meng, Yan; Su, Liang; Shi, Huiping; Huang, Shangzhi

    2010-08-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) and transmitted as an autosomal recessive trait. This is the first systematic mutation screen in Chinese MPS IVA patients. Mutation detections in 24 unrelated Chinese MPS IVA patients were performed by PCR and direct sequencing of exons or the mRNA of GALNS. A total of 42 mutant alleles were identified, belonging to 27 different mutations. Out of the 27 mutations, 16 were novel, including 2 splicing mutations (c.567-1G>T and c.634-1G>A), 2 nonsense mutations (p.W325X and p.Q422X) and 12 missense mutations (p.T88I, p.H142R, p.P163H, p.G168L, p.H236D, p.N289S, p.T312A, p.G316V, p.A324E, p.L366P, p.Q422K and p.F452L). p.G340D was found to be a common mutation in the Chinese MPS IVA patients, accounting for 16.7% of the total number of mutant alleles. The results show that the mutations in Chinese MPS IVA patients are also family specific but have a different mutation spectrum as compared to those of other populations.

  17. Sharing a bowl of tea.

    Science.gov (United States)

    Sen, S

    1993-06-01

    Soshitsu Sen's keynote speech before a symposium on population and the environment is summarized unofficially by the editorial staff. The instability of human thinking is given as the cause for the present destruction of the environment. In a visit to the His Majesty King of Sweden, Sen remarked that stabilizing human minds can be achieved within the tea ceremony through "serving tea heartily, receiving it with gratitude, and offering it to another." In this way, the spirit of concern for others can be practiced in everyday life and tranquility of mind reached. News broadcasts of starving parents and children as victims of civil war are disheartening. The Japanese people are not suffering such hunger, even though the economy has not been as robust as desired. The analogy is provided in the story by Chuang Chou about King Hun Dun and King Xiu and man's good intentions, which nonetheless destroy the earth. Japan has experienced forest and environmental destruction on the road to economic prosperity and satisfaction of self-interests. The advice on living in accord with nature is to appreciate each season for its own changes. For example, when it is the winter season, the complaint is about the cold and the desire is for spring; but when spring comes, the desire is for the cooler weather of fall. the ordinary way is to appreciate all seasons and is the best way of sustaining a healthy environment. In the garden of the tea hut, humans enter without their worldly title, position, and means; at the water basin, hands and mouth are cleansed, and entrance is made through a small hole into the hut much the same as emerging from the womb. Worldly matters are dispensed with and purity of thought is shared in the sharing of the bowl of green tea, saying "after you" to one another. Christianity and the Way of Tea share the same symbols of purification. The black tea bowl is in harmony with the green tea. Fatigue is relieved when gazing upon the color green; examples are given

  18. Hadron therapy information sharing prototype

    CERN Document Server

    Roman, Faustin Laurentiu; Kanellopoulos, Vassiliki; Amoros, Gabriel; Davies, Jim; Dosanjh, Manjit; Jena, Raj; Kirkby, Norman; Peach, Ken; Salt, Jose

    2013-01-01

    The European PARTNER project developed a prototypical system for sharing hadron therapy data. This system allows doctors and patients to record and report treatment-related events during and after hadron therapy. It presents doctors and statisticians with an integrated view of adverse events across institutions, using open-source components for data federation, semantics, and analysis. There is a particular emphasis upon semantic consistency, achieved through intelligent, annotated form designs. The system as presented is ready for use in a clinical setting, and amenable to further customization. The essential contribution of the work reported here lies in the novel data integration and reporting methods, as well as the approach to software sustainability achieved through the use of community-supported open-source components.

  19. Financial Assets [share, bonds] & Ancylia

    Science.gov (United States)

    Maksoed, Wh-

    2016-11-01

    Instead Elaine Scarry: "Thermonuclear monarchy" reinvent Carry Nation since Aug 17, 1965 the Republic of Indonesia's President speech: "Reach to the Star", for "cancellation" usually found in External Debt herewith retrieved from "the Window of theWorld": Ancylia, feast in March, a month named after Mars, the god of war. "On March 19 they used to put on their biggest performance of gymnastics in order to "bribe" their god for another good year", further we have vacancy & "vacuum tube"- Bulat Air karena Pembuluh, Bulat Kata karena Mufakat" proverb from Minangkabau, West Sumatra. Follows March 19, 1984 are first prototype flight of IAI Astra Jet as well as March 19, 2012 invoice accompanies Electric car Kujang-193, Fainancial Assets [share, bonds] are the answer for "infrastructure" & state owned enterprises assets to be hedged first initial debt per capita accordances. Heartfelt gratitudes to HE. Mr. Ir. Sarwono Kusumaatmadja/PT. Smartfren INDONESIA.

  20. Markets Share Models for EVs

    DEFF Research Database (Denmark)

    Jensen, Thomas Christian; Christensen, Linda

    of a logit choice model and based on the estimated parameters a simulation model is set up. The model will be available for assessing different scenarios and forecasts of the sales of EVs under different assumptions of prices of the cars, life-time of batteries, the operations costs, the driving range......-tion potential. The recent development has increased the knowledge of costs of stations and cars, but the knowledge of the market potential of EVs is still limited. In the traffic agreement of January 2009 electric vehicles were highlighted as part of the solution for future CO2 problems. Here, the target...... to the end of 2015. More ambitious greenhouse gas reductions are announced and EV’s may contrib-ute to such targets. However, no specific target has been set for the share of electric vehicles. In order to investigate the potential role of electric vehicles (EVs), DTU transport has construct-ed a small car...

  1. Sharing Knowledge across the Mediterranean

    CERN Multimedia

    2004-01-01

    On the occasion of CERN's 50th anniversary, the French Association for the Advancement of Science (AFAS) is organising a conference at CERN on 6 - 7 May on the subject of "Sharing Knowledge across the Mediterranean". The full program can be found at http://www.avancement-sciences.org. For those wishing to attend, advanced registration is mandatory. Follow the instructions at: http://lpsc.in2p3.fr/congres/CERN/index.htm The conference fee is 50 euro. It includes attendance at the official dinner on Thursday 6 May and a copy of the conference proceedings. Special conditions for CERN: registration is free, but does not include the dinner. CERN people wishing to receive the proceedings will be charged 10 euro.

  2. "Sharing Knowledge across the Mediterranean"

    CERN Multimedia

    2004-01-01

    On the occasion of CERN's 50th anniversary, the French Association for the Advancement of Science (AFAS) is organising a conference at CERN on 6 - 7 May on the subject of "Sharing Knowledge across the Mediterranean". The full program can be found at http://www.avancement-sciences.org. For those wishing to attend, advanced registration is mandatory. Follow the instructions at: http://lpsc.in2p3.fr/congres/CERN/index.htm The conference fee is 50 euro. It includes attendance at the official dinner on Thursday 6 May and a copy of the conference proceedings. Special conditions for CERN: registration is free, but does not include the dinner. CERN people wishing to receive the proceedings will be charged 10 euro.

  3. Sharing Space Situational Awareness Data

    Science.gov (United States)

    Bird, D.

    2010-09-01

    The Commander, United States Strategic Command (CDRUSSTRATCOM) accepted responsibility for sharing space situational awareness (SSA) information/services with commercial & foreign entities from the US Air Force on 22 Dec 09 (formerly the Commercial & Foreign Entities Pilot Program). The requirement to share SSA services with non-US Government (USG) entities is derived from Title 10, United States Code, Section 2274 (2010) and is consistent with the new National Space Policy. US Strategic Command’s (USSTRATCOM’s) sharing of SSA services consists of basic services (Two-Line Elements, decay data and satellite catalog details) available on www.space-track.org and advanced services (conjunction assessment, launch support, etc) available with a signed agreement. USSTRATCOM has requested USG permission to enter into international agreements to enable SSA data exchange with our foreign partners. USSTRATCOM recently authorized Joint Functional Component Command for Space (JFCC SPACE) to share Conjunction Summary Messages (CSMs) with satellite owner/operators whose satellites have been identified as closely approaching another space object. CSMs contain vector and covariance data computed using Special Perturbations theory. To facilitate the utility of the CSMs, USSTRATCOM has and is hosting CSM Workshops to ensure satellite operators fully understand the data contained in the CSM in order to provide an informed recommendation to their leadership. As JFCC SPACE matures its ability to accept ephemeris data from a satellite operator, it will be necessary to automatically transfer that data from one security level to another. USSTRATCOM and Air Force Space Command are coordinating the integration of a cross domain solution that will allow JFCC SPACE to do just that. Finally, USSTRATCOM is also working with commercial and governmental organizations to develop an internationally-accepted conjunction assessment message. The United States Government (USG), specifically the

  4. Platform-Independent Courseware Sharing

    Directory of Open Access Journals (Sweden)

    Takao Shimomura

    2013-04-01

    Full Text Available Courseware distribution between different platforms is the major issue of current e-Learning. SCORM (Sharable Content Object Reference Model is one of the solutions for courseware sharing. However, to make SCORM-conformable courseware, some knowledge about HTML and JavaScript is required. This paper presents a SWF (Sharable Web Fragment-based e-Learning system, where courseware is created with sharable Web fragments such as Web pages, images and other resources, and the courseware can be distributed to another platform by export and import facilities. It also demonstrates how to export a subject that contains assignments and problems and how to import the whole subject, only the assignments, or only the problems. The exported meta-information is architecture-independent and provides a model of courseware distribution.

  5. Sharing Experiences of Intercountry Adoption

    DEFF Research Database (Denmark)

    Raudaskoski, Pirkko; McIlvenny, Paul

    , signs, artefacts) to actualise this experience and enable action in the world. Intercountry adoption can be approached as a nexus of local and global practices which are mediated in talk, text and other modalities of discourse. We use mediated discourse analysis combined with conversation analysis...... to investigate the ways in which the experience of adoption is negotiated and shared in embodied interaction, drawing upon a variety of multimodal resources and mediational means. We are particularly interested in how experiences of adoption are localised, collected and dispersed. One of the aims...... of this research is to better understand the relationships between multimodality, embodiment, interaction and affect. We present the results of our analysis of how the experiences of adoptive parents are (re)mediated in a Danish television documentary series following five prospective adoptive couples, not all...

  6. Hadron therapy information sharing prototype.

    Science.gov (United States)

    Roman, Faustin Laurentiu; Abler, Daniel; Kanellopoulos, Vassiliki; Amoros, Gabriel; Davies, Jim; Dosanjh, Manjit; Jena, Raj; Kirkby, Norman; Peach, Ken; Salt, Jose

    2013-07-01

    The European PARTNER project developed a prototypical system for sharing hadron therapy data. This system allows doctors and patients to record and report treatment-related events during and after hadron therapy. It presents doctors and statisticians with an integrated view of adverse events across institutions, using open-source components for data federation, semantics, and analysis. There is a particular emphasis upon semantic consistency, achieved through intelligent, annotated form designs. The system as presented is ready for use in a clinical setting, and amenable to further customization. The essential contribution of the work reported here lies in the novel data integration and reporting methods, as well as the approach to software sustainability achieved through the use of community-supported open-source components.

  7. Parkinson disease: α-synuclein mutational screening and new clinical insight into the p.E46K mutation.

    Science.gov (United States)

    Pimentel, Márcia M G; Rodrigues, Fabíola C; Leite, Marco Antônio A; Campos Júnior, Mário; Rosso, Ana Lucia; Nicaretta, Denise H; Pereira, João S; Silva, Delson José; Della Coletta, Marcus V; Vasconcellos, Luiz Felipe R; Abreu, Gabriella M; Dos Santos, Jussara M; Santos-Rebouças, Cíntia B

    2015-06-01

    Amongst Parkinson's disease-causing genetic factors, missense mutations and genomic multiplications in the gene encoding α-synuclein are well established causes of the disease, although genetic data in populations with a high degree of admixture, such as the Brazilian one, are still scarce. In this study, we conducted a molecular screening of α-synuclein point mutations and copy number variation in the largest cohort of Brazilian patients with Parkinson's disease (n = 549) and also in twelve Portuguese and one Bolivian immigrants. Genomic DNA was isolated from peripheral blood leukocytes or saliva, and the mutational screening was performed by quantitative and qualitative real-time PCR. The only alteration identified was the p.E46K mutation in a 60-year-old man, born in Bolivia, with a familial history of autosomal dominant Parkinson's disease. This is the second family ever reported, in which this rare pathogenic mutation is segregating. The same mutation was firstly described ten years ago in a Spanish family with a neurodegenerative syndrome combining parkinsonism, dementia and visual hallucinations. The clinical condition of our proband reveals a less aggressive phenotype than previously described and reinforces that marked phenotypic heterogeneity is common among patients with Parkinson's disease, even among those carriers sharing the same mutation. Our findings add new insight into the preexisting information about α-synuclein p.E46K, improving our understanding about the endophenotypes associated to this mutation and corroborate that missense alterations and multiplications in α-synuclein are uncommon among Brazilian patients with Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. SharePoint 2013 for dummies

    CERN Document Server

    Withee, Ken

    2013-01-01

    The bestselling guide on running SharePoint, now updated to cover all the new features of SharePoint 2013 SharePoint Portal Server is an essential part of the enterprise infrastructure for many businesses. Building on the success of previous versions of SharePoint For Dummies, this new edition covers all the latest features of SharePoint 2013 and provides you with an easy-to-understand resource for making the most of all that this version has to offer. You'll learn how to get a site up and running, branded, and populated with content, workflow, and management. In addition, t

  9. Payoff Shares in Two-Player Contests

    Directory of Open Access Journals (Sweden)

    Samuel Häfner

    2016-09-01

    Full Text Available In imperfectly discriminating contests with symmetric valuations, equilibrium payoffs are positive shares of the value of the prize. In contrast to a bargaining situation, players’ shares sum to less than one because a residual share of the value is lost due to rent dissipation. In this paper, we consider contests with two players and investigate the relationship between these equilibrium shares and the parameters of a class of asymmetric Tullock contest success functions. Our main finding is that any players’ shares that sum up to less than one can arise as the unique outcome of a pure-strategy Nash equilibrium for appropriate parameters.

  10. Pro SharePoint 2010 Search

    CERN Document Server

    Noble, J; Bakman-Mikalski, Dan

    2011-01-01

    Pro SharePoint 2010 Search gives you expert advice on planning, deploying and customizing searches in SharePoint 2010. Drawing on the authors' extensive experience of working with real-world SharePoint deployments, this book teaches everything you'll need to know to create well-designed SharePoint solutions that always keep the end-user's experience in mind. Increase your search efficiency with SharePoint 2010's search functionality: extend the search user interface using third-party tools, and utilize analytics to improve relevancy. This practical hands-on book is a must-have resource for any

  11. Pro SharePoint 2013 administration

    CERN Document Server

    Garrett, Robert

    2013-01-01

    Pro SharePoint 2013 Administration is a practical guide to SharePoint 2013 for intermediate to advanced SharePoint administrators and power users, covering the out-of-the-box feature set and capabilities of Microsoft's collaboration and business productivity platform. SharePoint 2013 is an incredibly complex product, with many moving parts, new features, best practices, and 'gotchas.' Author Rob Garrett distills SharePoint's portfolio of features, capabilities, and utilities into an in-depth professional guide-with no fluff and copious advice-that is designed from scratch to be the manual Micr

  12. The Development of Recipient-Dependent Sharing Behavior and Sharing Expectations in Preschool Children

    Science.gov (United States)

    Paulus, Markus; Moore, Chris

    2014-01-01

    This study investigated the development of sharing expectations and sharing behavior in 3 groups of 3-, 4-, and 5-year-old children. We examined (a) whether preschool children expect a person to share more with a friend than with a disliked peer and (b) whether their expectation about others' sharing behavior depends on whether there is a cost or…

  13. Mapping preclinical compensation in Parkinson's disease: an imaging genomics approach

    DEFF Research Database (Denmark)

    van Nuenen, Bart F L; van Eimeren, Thilo; van der Vegt, Joyce P M

    2009-01-01

    Mutations in the Parkin (PARK2) and PINK1 gene (PARK 6) can cause recessively inherited Parkinson's disease (PD). The presence of a single Parkin or PINK1 mutation is associated with a dopaminergic nigrostriatal dysfunction and conveys an increased risk to develop PD throughout lifetime. Therefore...

  14. Compulsory acquisition of shares buyer, other shareholders, abuse of right of compulsory acquisition of shares

    Directory of Open Access Journals (Sweden)

    Arsić Zoran V.

    2015-01-01

    Full Text Available Company Act of Republic of Serbia includes mechanism for the compulsory acquisition of the shareholdings of minority shareholders. Technically this procedure is effected on the basis of the shareholders assembly resolution. Buyer is shareholder who has at least 90% of share capital and at least 90% of votes. Shares owned by entity under his dominant influence will be treated as shares of that shareholder provided that dominant influence exists at least one year. Company's own shares, and shares subject o a pledge do not represent shares of other shareholders. There are several actions which may be treated as abuse of right of compulsory acquisition of shares.

  15. Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing

    Directory of Open Access Journals (Sweden)

    Uta Francke

    2013-02-01

    Full Text Available Background. Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. Benefits and risks of providing this information directly to consumers are unknown.Methods. To assess and quantify emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service® report of three BRCA mutations that are common in Ashkenazi Jews, we invited all 136 BRCA1 and BRCA2 mutation-positive individuals in the 23andMe customer database who had chosen to view their BRCA reports to participate in this IRB-approved study. We also invited 160 mutation-negative customers who were matched for age, sex and ancestry. Semi-structured phone interviews were completed for 32 mutation carriers, 16 women and 16 men, and 31 non-carriers. Questions addressed personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of the result, emotional responses, perception of personal cancer risk, information sharing, and actions taken or planned.Results. Eleven women and 14 men had received the unexpected result that they are carriers of a BRCA1 185delAG or 5382insC, or BRCA2 6174delT mutation. None of them reported extreme anxiety and four experienced moderate anxiety that was transitory. Remarkably, five women and six men described their response as neutral. Most carrier women sought medical advice and four underwent risk-reducing procedures after confirmatory mutation testing. Male carriers realized that their test results implied genetic risk for female relatives, and several of them felt considerably burdened by this fact. Sharing mutation information with family members led to screening of at least 30 relatives and identification of 13 additional carriers. Non-carriers did not report inappropriate actions, such as foregoing cancer screening. All but one of the 32 mutation

  16. Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing.

    Science.gov (United States)

    Francke, Uta; Dijamco, Cheri; Kiefer, Amy K; Eriksson, Nicholas; Moiseff, Bianca; Tung, Joyce Y; Mountain, Joanna L

    2013-01-01

    Background. Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. Benefits and risks of providing this information directly to consumers are unknown. Methods. To assess and quantify emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service(®) report of three BRCA mutations that are common in Ashkenazi Jews, we invited all 136 BRCA1 and BRCA2 mutation-positive individuals in the 23andMe customer database who had chosen to view their BRCA reports to participate in this IRB-approved study. We also invited 160 mutation-negative customers who were matched for age, sex and ancestry. Semi-structured phone interviews were completed for 32 mutation carriers, 16 women and 16 men, and 31 non-carriers. Questions addressed personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of the result, emotional responses, perception of personal cancer risk, information sharing, and actions taken or planned. Results. Eleven women and 14 men had received the unexpected result that they are carriers of a BRCA1 185delAG or 5382insC, or BRCA2 6174delT mutation. None of them reported extreme anxiety and four experienced moderate anxiety that was transitory. Remarkably, five women and six men described their response as neutral. Most carrier women sought medical advice and four underwent risk-reducing procedures after confirmatory mutation testing. Male carriers realized that their test results implied genetic risk for female relatives, and several of them felt considerably burdened by this fact. Sharing mutation information with family members led to screening of at least 30 relatives and identification of 13 additional carriers. Non-carriers did not report inappropriate actions, such as foregoing cancer screening. All but one of the 32 mutation-positive participants

  17. Filaggrin mutations and the skin

    Directory of Open Access Journals (Sweden)

    Dipankar De

    2012-01-01

    Full Text Available Filaggrin is very important in the terminal differentiation of the skin and the formation of cornified envelope in the stratum corneum. Several mutations in the filaggrin gene have been identified in the last decade, mostly from the European countries. Loss of function mutations in the filaggrin gene results in reduced production of filaggrin, depending on the type and site of mutation. Such mutations in the filaggrin gene have been shown to be the most significant genetic risk factor for development of atopic dermatitis and undoubtedly has a role in the pathogenesis of ichthyosis vulgaris. Though there is theoretical possibility of association with hand eczema and allergic contact dermatitis; in clinical studies, the strength of these associations was not significantly strong. In this review, we have discussed the structure and function of filaggrin, basic genetics, type of mutations in filaggrin gene, and association of such mutations with different dermatoses.

  18. Muller's ratchet with compensatory mutations

    CERN Document Server

    Pfaffelhuber, Peter; Wakolbinger, Anton

    2011-01-01

    We consider an infinite dimensional system of stochastic differential equations which describes the evolution of type frequencies in a large population. Random reproduction is modeled by a Wright-Fisher noise whose inverse diffusion coefficient $N$ corresponds to the total population size. The type of an individual is the number $k$ of deleterious mutations it carries. We assume that fitness of individuals carrying $k$ mutations is decreased by $\\alpha k$ for some $\\alpha >0$. Along the individual lines of descent, (new) mutations accumulate at rate $\\lambda$ per generation, and each of these mutations has a small probability $\\gamma$ per generation to disappear. While the case $\\gamma =0 $ is known as (the Fleming-Viot version of) {\\em Muller's ratchet}, the case $\\gamma > 0$ is referred to as that of {\\em compensatory mutations} in the biological literature. In the former case ($\\gamma=0$), an ever increasing number of mutations is accumulated over time, while in the latter ($\\gamma > 0$) this is prevented ...

  19. Filaggrin mutations and the skin.

    Science.gov (United States)

    De, Dipankar; Handa, Sanjeev

    2012-01-01

    Filaggrin is very important in the terminal differentiation of the skin and the formation of cornified envelope in the stratum corneum. Several mutations in the filaggrin gene have been identified in the last decade, mostly from the European countries. Loss of function mutations in the filaggrin gene results in reduced production of filaggrin, depending on the type and site of mutation. Such mutations in the filaggrin gene have been shown to be the most significant genetic risk factor for development of atopic dermatitis and undoubtedly has a role in the pathogenesis of ichthyosis vulgaris. Though there is theoretical possibility of association with hand eczema and allergic contact dermatitis; in clinical studies, the strength of these associations was not significantly strong. In this review, we have discussed the structure and function of filaggrin, basic genetics, type of mutations in filaggrin gene, and association of such mutations with different dermatoses.

  20. Business models of sharing economy companies : exploring features responsible for sharing economy companies’ internationalization

    OpenAIRE

    Kosintceva, Aleksandra

    2016-01-01

    This paper is dedicated to the sharing economy business models and their features responsible for internationalization. The study proposes derived definitions for the concepts of “sharing economy” and “business model” and first generic sharing economy business models typology. The typology was created through the qualitative analysis of secondary data on twenty sharing economy companies from nine different industries. The outlined categories of sharing economy business models a...

  1. AIP mutation in pituitary adenomas in the 18th century and today.

    Science.gov (United States)

    Chahal, Harvinder S; Stals, Karen; Unterländer, Martina; Balding, David J; Thomas, Mark G; Kumar, Ajith V; Besser, G Michael; Atkinson, A Brew; Morrison, Patrick J; Howlett, Trevor A; Levy, Miles J; Orme, Steve M; Akker, Scott A; Abel, Richard L; Grossman, Ashley B; Burger, Joachim; Ellard, Sian; Korbonits, Márta

    2011-01-06

    Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.

  2. MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43).

    Science.gov (United States)

    Depondt, Chantal; Donatello, Simona; Rai, Myriam; Wang, François Charles; Manto, Mario; Simonis, Nicolas; Pandolfo, Massimo

    2016-10-01

    To identify the causative gene mutation in a 5-generation Belgian family with dominantly inherited spinocerebellar ataxia and polyneuropathy, in which known genetic etiologies had been excluded. We collected DNA samples of 28 family members, including 7 living affected individuals, whose clinical records were reviewed by a neurologist experienced in ataxia. We combined linkage data of 21 family members with whole exome sequencing in 2 affected individuals to identify shared heterozygous variants mapping to potentially linked regions. Variants were screened for rarity and for predicted damaging effect. A candidate mutation was confirmed by Sanger sequencing and tested for cosegregation with the disease. Affected individuals presented with late-onset sensorimotor axonal polyneuropathy; all but one also had cerebellar ataxia. We identified a variant in the MME gene, p.C143Y, that was absent from control databases, cosegregated with the phenotype, and was predicted to have a strong damaging effect on the encoded protein by all algorithms we used. MME encodes neprilysin (NEP), a zinc-dependent metalloprotease expressed in most tissues, including the central and peripheral nervous systems. The mutated cysteine 143 forms a disulfide bridge, which is 100% conserved in NEP and in similar enzymes. The recent identification of recessive MME mutations in 10 unrelated individuals from Japan with axonal polyneuropathy further supports the causality of the mutation, despite the dominant mode of inheritance and the presence of cerebellar involvement in our study family. Functional studies are needed to identify the mechanisms underlying these differences.

  3. Mutations induced in plant breeding

    Energy Technology Data Exchange (ETDEWEB)

    Barriga B, P. (Universidad Austral de Chile, Valdivia. Inst. de Produccion y Sanidad Vegetal)

    1984-10-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented.

  4. Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations.

    Science.gov (United States)

    Charfeddine, C; Monastiri, K; Mokni, M; Laadjimi, A; Kaabachi, N; Perin, O; Nilges, M; Kassar, S; Keirallah, M; Guediche, M N; Kamoun, M R; Tebib, N; Ben Dridi, M F; Boubaker, S; Ben Osman, A; Abdelhak, S

    2006-06-01

    Tyrosinemia type II or Richner-Hanhart Syndrome (RHS) is an autosomal recessive disorder characterized by keratitis, palmoplantar keratosis, mental retardation, and elevated blood tyrosine levels. The disease is due to a deficiency of hepatic cytosolic tyrosine aminotransferase (TATc), an enzyme involved in the tyrosine catabolic pathway. Because of the high rate of consanguinity this disorder seems to be relatively common among the Arab and Mediterranean populations. RHS is characterized by inter and intrafamilial phenotypic variability. A large spectrum of mutations within TATc gene has been shown to be responsible for RHS. In the present study, we report the clinical features and the molecular investigation of RHS in three unrelated consanguineous Tunisian families including 7 patients with confirmed biochemical diagnosis of tyrosinemia type II. Mutation analyses were performed and two novel missense mutations were identified (C151Y) and (L273P) within exon 5 and exon 8, respectively. The 3D-structural characterization of these mutations provides evidence of defective folding of the mutant proteins, and likely alteration of the enzymatic activity. Phenotype variability was observed even among individuals sharing the same pathogenic mutation.

  5. A low proportion of BRCA2 mutations in Finnish breast cancer families.

    Science.gov (United States)

    Vehmanen, P; Friedman, L S; Eerola, H; Sarantaus, L; Pyrhönen, S; Ponder, B A; Muhonen, T; Nevanlinna, H

    1997-05-01

    One hundred breast cancer families were identified at the Helsinki University Central Hospital in Finland and were screened for germ-line mutations in the coding regions and splice boundaries of the BRCA2 gene. Eight families (8%) were found to carry five different mutations, all of which are predicted to prematurely truncate the protein product. These BRCA2 families have early-onset breast cancer (mean and median age = 49 years), with four of the eight families including ovarian cancer but with no families including male breast cancer. A wide spectrum of other cancers also is seen in these families. Three mutations were identified in more than one family, and haplotype analysis in the families suggested a common founder for each recurrent mutation. One recurrent mutation, 999del5, previously has been noted as a common mutation in Iceland. The relationship between the Icelandic 999del5 mutation and the Finnish 999del5 mutation was explored by comparison of families from both countries. A common haplotype covering a minimal region intragenic to the BRCA2 gene was shared between the Icelandic and the Finnish mutation carriers.

  6. SharePoint 2007 Collaboration For Dummies

    CERN Document Server

    Harvey, Greg

    2009-01-01

    If you're looking for a way to help your teams access what they need to know, work together, and get the job done, SharePoint can do just that. SharePoint 2007 Collaboration For Dummies shows you the easiest way to set up and customize SharePoint, manage your data, interact using SharePoint blogs and wikis, integrate Office programs, and make your office more productive. You'll learn what SharePoint can do and how to make it work for your business, understand the technical terms, and enable your people to collaborate on documents and spreadsheets. You'll even discover how to get SharePoint hel

  7. FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Sara A Byron

    Full Text Available Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI and clinicopathological features including overall survival (OS and disease-free survival (DFS were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466; KRAS (87/464; CTNNB1 (88/454 and PIK3CA (104/464. KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05 and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002. Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06 towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II, FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008 and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025 and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045. In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

  8. Linear multi-secret sharing schemes

    Institute of Scientific and Technical Information of China (English)

    XIAO Liangliang; LIU Mulan

    2005-01-01

    In this paper the linear multi-secret sharing schemes are studied by using monotone span programs. A relation between computing monotone Boolean functions by using monotone span programs and realizing multi-access structures by using linear multisecret sharing schemes is shown. Furthermore, the concept of optimal linear multi-secret sharing scheme is presented and the several schemes are proved to be optimal.

  9. Knowledge sharing in a competence intensive company

    OpenAIRE

    Johnsson, Matilda

    2015-01-01

    The overall purpose of this study is to investigate a competence intensive company, evaluating their knowledge sharing. By identifying barriers and in what way IT can have a positive impact on the knowledge sharing, the study investigates how knowledge can be shared more efficiently within the company. A thorough case study was conducted and furthermore analysed with respect to a model proposed by the author. The model consist of three dimensions of knowledge creation, the “how, where and wha...

  10. One Share - One Vote: The Theory

    OpenAIRE

    2007-01-01

    The impact of separating cash flow and votes depends on the ownership structure. In widely held firms, one share - one vote is in general not optimal. While it ensures an efficient outcome in bidding contests, dual-class shares mitigate the free-rider problem, thereby promoting takeovers. In the presence of a controlling shareholder, one share - one vote promotes value-increasing control transfers and deters value-decreasing control transfers more effectively than any other vote allocation. M...

  11. The Cross-Cultural Knowledge Sharing Challenge

    DEFF Research Database (Denmark)

    Persson, John Stouby

    2013-01-01

    Cross-cultural offshoring in software development challenges effective knowledge sharing. While research has suggested temporarily co-locating participants to address this challenge, few studies are available on what knowledge sharing practices emerge over time when co-locating cross-cultural sof......Cross-cultural offshoring in software development challenges effective knowledge sharing. While research has suggested temporarily co-locating participants to address this challenge, few studies are available on what knowledge sharing practices emerge over time when co-locating cross......-cultural software developers. This paper presents a longitudinal case study of an offshoring project with co-location of Indian and Danish software developers for 10½ months. A community-of-practice (CoP) analysis is offered of what knowledge sharing practices emerge over time and how these where facilitated...... period of colocation four facilitators of cross-cultural knowledge sharing were shared office, shared responsibility for tasks and problems, shared prioritization of team spirit, and a champion of social integration....

  12. Beginning SharePoint 2010 Development

    CERN Document Server

    Fox, Steve

    2010-01-01

    Discover how to take advantage of the many new features in SharePoint 2010. SharePoint provides content management (enterprise content management, Web content management, records management, and more), workflow, and social media features, and the new version boasts enhanced capabilities. This introductory-level book walks you through the process of learning, developing, and deploying SharePoint 2010 solutions. You'll leverage your existing skills and tools to grasp the fundamental programming concepts and practices of SharePoint 2010. The author clearly explains how to develop your first appli

  13. Communications and Information Sharing (CIS) Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — TheCommunications and Information Sharing (CIS) Laboratory is a Public Safety interoperable communications technology laboratory with analog and digital radios, and...

  14. Mastering Microsoft SharePoint Foundation 2010

    CERN Document Server

    Callahan, C A

    2011-01-01

    Everything IT professionals need to create collaborative solutions. SharePoint Foundation 2010 is the newest version of a powerful collaboration tool used in many Exchange-enabled organizations. This book gets network professionals and business application administrators up to speed on the updates, features, and installation procedures, preparing them to create powerful collaboration structures for their companies.: Microsoft SharePoint Foundation 2010 is the successor to Windows SharePoint Services 3.0 and is used with Microsoft Office SharePoint Server to enable collaboration; this guide pre

  15. Cheater identifiable visual secret sharing scheme

    Institute of Scientific and Technical Information of China (English)

    Gan Zhi; Chen Kefei

    2005-01-01

    The visual secret sharing scheme proposed by Naor and Shamir provides a way to encrypt a secret black-white image into shares. A qualified group of participants can recover the secret message without using any cryptographic computation. But the original scheme can easily be corrupted by malicious participant. We propose an extension of VSS(visual secret sharing) to identify cheaters before the secret is recovered. Without the need for any additional information and cryptographic computation, every participant can verify the validity of shares of other participants, thus the security of VSS is enhanced.

  16. You Share, I Share: Network Effects and Economic Incentives in P2P File-Sharing System

    CERN Document Server

    Salek, Mahyar; Kempe, David

    2011-01-01

    We study the interaction between network effects and external incentives on file sharing behavior in Peer-to-Peer (P2P) networks. Many current or envisioned P2P networks reward individuals for sharing files, via financial incentives or social recognition. Peers weigh this reward against the cost of sharing incurred when others download the shared file. As a result, if other nearby nodes share files as well, the cost to an individual node decreases. Such positive network sharing effects can be expected to increase the rate of peers who share files. In this paper, we formulate a natural model for the network effects of sharing behavior, which we term the "demand model." We prove that the model has desirable diminishing returns properties, meaning that the network benefit of increasing payments decreases when the payments are already high. This result holds quite generally, for submodular objective functions on the part of the network operator. In fact, we show a stronger result: the demand model leads to a "cov...

  17. Wrox SharePoint 2010 SharePoint911 three-pack

    CERN Document Server

    Klindt, Todd; Mason, Jennifer; Rogers, Laura; Drisgill, Randy; Ross, John; Riemann, Larry; Perran, Amanda; Perran, Shane; Sanford, Jacob J; Stubbs, Paul; Caravajal, Steve

    2012-01-01

    The Wrox SharePoint 2010 SharePoint911 Three-Pack combines the contents of three full e-books written by the experts from SharePoint911.  That's over 1800 pages of hands-on advice from Todd Klindt, Shane Young, Laura Rogers, Randy Drisgill, Jennifer Mason, John Ross, and Larry Riemann, among others. In Beginning SharePoint 2010: Building Business Solutions with SharePoint (ISBN 978-0-470-61789-2) by Amanda Perran, Shane Perran, Jennifer Mason, and Laura Rogers, readers learn the core concepts, terminology, and features of SharePoint 2010. In Professiona

  18. Beginning SharePoint 2010 Building Business Solutions with SharePoint

    CERN Document Server

    Perran, Amanda; Mason, Jennifer; Rogers, Laura

    2010-01-01

    Two SharePoint MVPs provide the ultimate introduction to SharePoint 2010Beginning SharePoint 2010: Building Team Solutions with SharePoint provides information workers and site managers with extensive knowledge and expert advice, empowering them to become SharePoint champions within their organizations.Provides expansive coverage of SharePoint topics, as well as specialty areas such as forms, excel services, records management, and web content managementDetails realistic usage scenarios, and includes practice examples that highlight best practices for configuration and customizationIncludes de

  19. MPL mutations in myeloproliferative disorders

    DEFF Research Database (Denmark)

    Beer, Philip A.; Campbell, Peter J.; Scott, Linda M.

    2008-01-01

    Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA...

  20. Identification of a Novel Mutation (867delA) in the Glucose-6-phosphatase Gene in Two Siblings with Glycogen Storage Disease Type Ia with Different Phenotypes

    NARCIS (Netherlands)

    Rake, Jan Peter; ten Berge, Annelies M.; Visser, Gepke; Verlind, Edwin; Niezen-Koning, Klary E.; Buys, Charles H. C. M.; Smit, G. Peter A.; Scheffer, Hans

    2000-01-01

    We identified a novel mutation (867delA) in the glucose-6-phosphatase gene of two siblings with glycogen storage disease type Ia. Although both siblings share the same mutations, their phenotype regarding adult height and hepatomegaly differs. In glycogen storage disease type Ia, substantial heterog

  1. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse.

    Science.gov (United States)

    Garg, Manoj; Nagata, Yasunobu; Kanojia, Deepika; Mayakonda, Anand; Yoshida, Kenichi; Haridas Keloth, Sreya; Zang, Zhi Jiang; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ding, Ling-Wen; Alpermann, Tamara; Sun, Qiao-Yang; Lin, De-Chen; Chien, Wenwen; Madan, Vikas; Liu, Li-Zhen; Tan, Kar-Tong; Sampath, Abhishek; Venkatesan, Subhashree; Inokuchi, Koiti; Wakita, Satoshi; Yamaguchi, Hiroki; Chng, Wee Joo; Kham, Shirley-Kow Yin; Yeoh, Allen Eng-Juh; Sanada, Masashi; Schiller, Joanna; Kreuzer, Karl-Anton; Kornblau, Steven M; Kantarjian, Hagop M; Haferlach, Torsten; Lill, Michael; Kuo, Ming-Chung; Shih, Lee-Yung; Blau, Igor-Wolfgang; Blau, Olga; Yang, Henry; Ogawa, Seishi; Koeffler, H Phillip

    2015-11-26

    Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. To identify the mutational spectrum associated with relapse, whole-exome sequencing was performed on 13 matched diagnosis, relapse, and remission trios followed by targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has an average of 13 mutations per sample, similar to other AML subtypes, which is a low mutation rate compared with that in solid tumors. Recurrent mutations occur in genes related to DNA methylation, chromatin, histone methylation, myeloid transcription factors, signaling, adhesion, cohesin complex, and the spliceosome. Their pattern of mutual exclusivity and cooperation among mutated genes suggests that these genes have a strong biological relationship. In addition, we identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1, FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific phase. DNMT3A mutations are the most stable mutations, and this DNMT3A-transformed clone can be present even in morphologic complete remissions. Of note, all AML matched trio samples shared at least 1 genomic alteration at diagnosis and relapse, suggesting common ancestral clones. Two types of clonal evolution occur at relapse: either the founder clone recurs or a subclone of the founder clone escapes from induction chemotherapy and expands at relapse by acquiring new mutations. Relapse-specific mutations displayed an increase in transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor-suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study clearly shows that FLT3-ITD AML requires additional driver genetic alterations in addition to FLT3-ITD alone.

  2. Ancient founder mutation is responsible for Imerslund-Gräsbeck Syndrome among diverse ethnicities

    Directory of Open Access Journals (Sweden)

    Beech Cameron M

    2011-11-01

    Full Text Available Abstract Background Imerslund-Gräsbeck syndrome (IGS was described just over 50 years ago by Olga Imerslund and Ralph Gräsbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl due to bi-allelic mutations in either the cubilin gene (CUBN or the human amnionless homolog (AMN. Mutations in the two genes are commonly seen in founder populations or in societies with a high degree of consanguineous marriages. One particular mutation in AMN, c.208-2A>G, causing an out-of-frame loss of exon 4 in the mRNA, is responsible for some 15% of IGS cases globally. We present evidence that this founder mutation causes a substantial percentage of cases among diverse ethnicities and that the mutation is as old as human civilization. Methods Partial genotyping indicated a founder event but its presence in diverse peoples of Arabic, Turkish, Jewish, and Hispanic ancestry suggested that the mutation might be recurrent. We therefore studied the flanking sequence spanning 3.5 Mb to elucidate the origin of the haplotype and estimate the age of the mutation using a Bayesian inference method based on observed linkage disequilibrium. Results The mutation's distribution, the size of the shared haplotype, and estimates of growth rate and carrier frequency indicated that the mutation was a single prehistoric event. Dating back to the ancient Middle East around 11,600 BC, the mutation predates the advent of writing, farming, and the monotheistic religions of the region. Conclusions This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related.

  3. Adaptive team formation for shared situation awareness

    NARCIS (Netherlands)

    Foeken, E. van; Kester, L.J.H.M.

    2012-01-01

    To reach their goals in the most effective way a team of entities needs to have a high situation awareness. In addition, the awareness needs to be shared among the entities and preferably identical in order to coordinate their actions. Unfortunately, optimal identical shared awareness is often not p

  4. Shared Leadership: Can It Work in Schools?

    Science.gov (United States)

    Lindahl, Ronald

    2008-01-01

    Over the past couple of decades, K-12 schools have courageously struggled with the concept of shared, or distributed, leadership; however, the basic landscape of K-12 school leadership remains heavily hierarchical. Nonetheless, teachers can share leadership. This article explores productive forms of teacher leadership that are models of…

  5. Another Kind of Diplomacy: International Resource Sharing

    Science.gov (United States)

    Arlitsch, Kenning; Lombardo, Nancy T.; Gregory, Joan M.

    2005-01-01

    Over the past six years, the University of Utah libraries have developed an extensive international presence through digital resource sharing. Services include instruction, electronic document delivery, shared catalogs, and full-text databases. This paper will describe the process of establishing, extending, and improving these services through…

  6. Revenue Sharing in European Football Leagues

    DEFF Research Database (Denmark)

    Olai Hansen, Bodil; Tvede, Mich

    2016-01-01

    of complementarities. Firstly, it is shown that revenue sharing leads to lower overall quality of sports leagues. Secondly, it is shown that the optimal quality for the league is lower (higher) than the quality in a league without revenue sharing in case of negative (positive) externalities between clubs. Thirdly...

  7. How suboptimal are linear sharing rules?

    DEFF Research Database (Denmark)

    Jensen, Bjarne Astrup; Nielsen, Jørgen Aase

    2016-01-01

    The objective of this paper is to analyze criteria for portfolio choice when two investors are forced to invest in a common portfolio and share the proceeds by a linear sharing rule. A similar situation with many investors is typical for defined contribution pension schemes. The restriction impli...

  8. Load sharing in models with communication delays

    NARCIS (Netherlands)

    Geest, R.A.B. van der

    1994-01-01

    Computer systems may be connected in a network to share workload. A control problem then is to decide which computer should carry out which task. Novel in this report is a model for load sharing with communication delays. It takes nonnegligible time for information from one computer to reach the oth

  9. Sharing tools and know-how

    DEFF Research Database (Denmark)

    Saad-Sulonen, Joanna

    In this position paper I address the theme of designing for sharing in self-organized urban communities by bringing forward the aspect of sharing tools and know-how. I report the lessons learned from a case in Helsinki and open questions for discussion regarding some of the identified challenges...

  10. IT-Support for Shared Care

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.; Kensing, Finn

    2005-01-01

    This paper describes work-in-progress to explore how informa-tion and communication technologies (ICT) can be designed and implemented to provide effective support of shared care programs. The purpose of the project is to develop generic models of shared care applications as well as organizational...

  11. Information Sharing for IT Security Professionals

    Science.gov (United States)

    Petersen, Rodney J.

    2008-01-01

    Information sharing is a core value for information technology (IT) security professionals. It is also a familiar concept for those who work at institutions of higher education because of their long history of collaboration and openness. Information sharing has become part of the national fabric as IT security professionals attempt to secure cyber…

  12. A Decision Model for Data Sharing

    NARCIS (Netherlands)

    Eckartz, S.; Hofman, W.J.; Veenstra, A.F. van

    2014-01-01

    Data-driven innovation has great potential for the development of innovative services that not only have economic value, but that help to address societal challenges. Many of these challenges can only be addressed by data sharing of public and privately owned data. These public-private data sharing

  13. Adaptive team formation for shared situation awareness

    NARCIS (Netherlands)

    Foeken, E. van; Kester, L.J.H.M.

    2012-01-01

    To reach their goals in the most effective way a team of entities needs to have a high situation awareness. In addition, the awareness needs to be shared among the entities and preferably identical in order to coordinate their actions. Unfortunately, optimal identical shared awareness is often not

  14. The Filtering Effect of Sharing Rules

    NARCIS (Netherlands)

    Dari Mattiacci, G.; de Geest, G.G.A.

    2004-01-01

    Sharing rules have a filtering effect on violations: they prevent the most harmful violations and let the least harmful ones occur. We show under what conditions the filtering effect improves social welfare and argue that this may explain why, in most areas of the law, sharing rules are, in general,

  15. The Political Economy of Intergenerational Risk Sharing

    NARCIS (Netherlands)

    Hollanders, D.A.

    2010-01-01

    This paper analyses the political constraints of intergenerational risk sharing. The rst result is that the political process generally does not lead to ex ante optimal insurance. The second result is that in a second best political setting PAYG still contributes to intergenerational risk sharing. T

  16. Putting the sharing economy into perspective

    NARCIS (Netherlands)

    Frenken, Koen; Schor, Juliet

    2017-01-01

    We develop a conceptual framework that allows us to define the sharing economy and its close cousins and we understand its sudden rise from an economic-historic perspective. We then assess the sharing economy platforms in terms of the economic, social and environmental impacts. We end with reflectio

  17. Challenges to complete and useful data sharing.

    Science.gov (United States)

    Mbuagbaw, Lawrence; Foster, Gary; Cheng, Ji; Thabane, Lehana

    2017-02-14

    Data sharing from clinical trials is one way of promoting fair and transparent conduct of clinical trials. It would maximise the use of data and permit the exploration of additional hypotheses. On the other hand, the quality of secondary analyses cannot always be ascertained, and it may be unfair to investigators who have expended resources to collect data to bear the additional burden of sharing. As the discussion on the best modalities of sharing data evolves, some of the practical issues that may arise need to be addressed. In this paper, we discuss issues which impede the use of data even when sharing should be possible: (1) multicentre studies requiring consent from all the investigators in each centre; (2) remote access platforms with software limitations and Internet requirements; (3) on-site data analysis when data cannot be moved; (4) governing bodies for data generated in one jurisdiction and analysed in another; (5) using programmatic data collected as part of routine care; (6) data collected in multiple languages; (7) poor data quality. We believe these issues apply to all primary data and cause undue difficulties in conducting analysis even when there is some willingness to share. They can be avoided by anticipating the possibility of sharing any clinical data and pre-emptively removing or addressing restrictions that limit complete sharing. These issues should be part of the data sharing discussion.

  18. 24 CFR 206.23 - Shared appreciation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Shared appreciation. 206.23 Section... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgages § 206.23 Shared appreciation. (a) Additional interest based on net appreciated value. Any mortgage for which the mortgagee has chosen...

  19. Simulation and analysis of shared extended mind

    NARCIS (Netherlands)

    Bosse, T.; Jonker, C.M.; Schut, M.C.; Treur, J.

    2008-01-01

    Some types of animals exploit patterns created in the environment as external mental states, thus obtaining an extension of their mind. In the case of social animals the creation and exploitation of such patterns can be shared, which supports a form of shared extended mind or collective intelligence

  20. A Decision Model for Data Sharing

    NARCIS (Netherlands)

    Eckartz, S.; Hofman, W.J.; Veenstra, A.F. van

    2014-01-01

    Data-driven innovation has great potential for the development of innovative services that not only have economic value, but that help to address societal challenges. Many of these challenges can only be addressed by data sharing of public and privately owned data. These public-private data sharing

  1. 12 CFR 5.67 - Fractional shares.

    Science.gov (United States)

    2010-01-01

    ... fractional shares. The bank may: (a) Issue scripts or warrants for trading; (b) Make reasonable arrangements... fair price upon the fraction not being issued through its sale, or the purchase of the additional... such stock is available; or (d) Sell full shares representing all the fractions at public auction, or...

  2. The Political Economy of Intergenerational Risk Sharing

    NARCIS (Netherlands)

    Hollanders, D.A.

    2010-01-01

    This paper analyses the political constraints of intergenerational risk sharing. The rst result is that the political process generally does not lead to ex ante optimal insurance. The second result is that in a second best political setting PAYG still contributes to intergenerational risk sharing. T

  3. Sharing tools and know-how

    DEFF Research Database (Denmark)

    Saad-Sulonen, Joanna

    In this position paper I address the theme of designing for sharing in self-organized urban communities by bringing forward the aspect of sharing tools and know-how. I report the lessons learned from a case in Helsinki and open questions for discussion regarding some of the identified challenges...

  4. Open Education, OER & MOOCs for entrepreneurship: To share or not to share

    NARCIS (Netherlands)

    Stracke, Christian M.

    2016-01-01

    Invited Speech at the Conference Skills and competences on female entrepreneurship, Athens, Greece, by Stracke, C. M. (2016, 6 July): "Open Education, OER & MOOCs for entrepreneurship: To share or not to share"

  5. Open Education, OER & MOOCs for entrepreneurship: To share or not to share

    NARCIS (Netherlands)

    Stracke, Christian M.

    2016-01-01

    Invited Speech at the Conference Skills and competences on female entrepreneurship, Athens, Greece, by Stracke, C. M. (2016, 6 July): "Open Education, OER & MOOCs for entrepreneurship: To share or not to share"

  6. Determinants of knowledge-sharing intention and knowledge-sharing behavior in a public organization

    Directory of Open Access Journals (Sweden)

    Delio Ignacio Castaneda

    2016-06-01

    Full Text Available The purpose of this paper is to examine the factors that affect the knowledge-sharing intention and knowledge-sharing behavior in a public sector organization. A survey was conducted with 188 knowledge workers of a public-sector organization at the national level in Colombia. In this public organization significant relationships between self-efficacy and knowledge-sharing intention, subjective norms, and knowledge-sharing behavior, and between knowledge-sharing intention and knowledge-sharing behavior were found. There was a direct effect of perceived organizational support on knowledge-sharing behavior and a moderator role of perceived organizational support between the studied variables. The findings clarify how some personal variables and perceived organizational support interact in the explanation of knowledge sharing.

  7. Mutational meltdown in laboratory yeast populations

    NARCIS (Netherlands)

    Zeyl, C.; Mizesko, M.; Visser, de J.A.G.M.

    2001-01-01

    In small or repeatedly bottlenecked populations, mutations are expected to accumulate by genetic drift, causing fitness declines. In mutational meltdown models, such fitness declines further reduce population size, thus accelerating additional mutation accumulation and leading to extinction. Because

  8. Shared decision-making in epilepsy management.

    Science.gov (United States)

    Pickrell, W O; Elwyn, G; Smith, P E M

    2015-06-01

    Policy makers, clinicians, and patients increasingly recognize the need for greater patient involvement in clinical decision-making. Shared decision-making helps address these concerns by providing a framework for clinicians and patients to make decisions together using the best evidence. Shared decision-making is applicable to situations where several acceptable options exist (clinical equipoise). Such situations occur commonly in epilepsy, for example, in decisions regarding the choice of medication, treatment in pregnancy, and medication withdrawal. A talk model is a way of implementing shared decision-making during consultations, and decision aids are useful tools to assist in the process. Although there is limited evidence available for shared decision-making in epilepsy, there are several benefits of shared decision-making in general including improved decision quality, more informed choices, and better treatment concordance. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. SharePoint 2010 Development For Dummies

    CERN Document Server

    Withee, Ken

    2011-01-01

    A much-needed guide that shows you how to leverage SharePoint tools without writing a line of code!. The great news about SharePoint is…you don't need to be a seasoned .NET developer to develop custom functions for it. This book shows you how to use SharePoint Designer, Report Builder, Dashboard Designer, InfoPath, Excel, Word, Visio, and the SharePoint web-based UI to design and develop—without ever writing a line of code! Learn how to customize your site, build SharePoint apps, start social networking, or add Web parts.  This straightforward guide makes everything easier.: Introduces you to

  10. Towards a Theory of Socially Shared Consumption

    DEFF Research Database (Denmark)

    Kunst, Katrine; Vatrapu, Ravi

    2014-01-01

    Recent years have seen an increased sharing of consumptive practices, experiences and evaluations on social media platforms. Such socially shared consumption can range from electronic word-of-mouth to formal online reviews as well as automated product mentions facilitated by social media...... applications Based on a review of extant emerging literature on this topic as well as of literature on relevant topics such as social influence, online reviews, theories of the extended self and conspicuous consumption, this paper proposes a new concept, “socially shared consumption” and a taxonomy for better...... understanding and analysing the growing phenomenon of consumers’ social sharing of consumption on social media platforms The taxonomy consists of five dimensions of socially shared consumption: Phase, Automation, Formality, Expressiveness, and Sentiment. The primary contributions of this research...

  11. Power-sharing: concepts, debates and gaps

    Directory of Open Access Journals (Sweden)

    Alexandre de Sousa Carvalho

    2016-05-01

    Full Text Available Academic literature tends to reflect the two main objectives of power-sharing: promoting the construction of sustainable peace and serving to structure the foundations for growth and development of democracy in divided societies. reflecting this, two dimensions and discourses of analysis and evaluation stand out: a classical dimension centred on power-sharing as theory and a normative proposal for democracy in divided societies, and another focused mainly on power-sharing as a meachanism of conflict management. This article aims to introduce the reader to discussions about power-sharing, reviewing and critically analysing power-sharing literature to show its gaps and tensions, as well as suggesting some points where one can continue the debate.

  12. Knowledge-Sharing Hostility and Governance Mechanisms

    DEFF Research Database (Denmark)

    Husted, Kenneth; Michailova, Snejina; Minbaeva, Dana

    2012-01-01

    knowledge-sharing behavior. The paper aims to examine how two specific knowledge-governance mechanisms – commitment-based and transaction-based mechanisms – affect knowledge sharing Design/methodology/approach – The authors test the hypotheses on a sample of 1,639 respondents in 15 organizations in Denmark....... Findings – The authors find that the use of transaction-based mechanisms promotes knowledge-sharing hostility by strengthening individuals' reasons for hoarding and rejecting knowledge, and by negatively affecting individuals' attitudes towards sharing knowledge about mistakes. In contrast, the use...... of commitment-based mechanisms diminishes knowledge-sharing hostility among individuals. Originality/value – The contribution of the paper is two-fold. First, it responds to the clear need to examine individual characteristics related to withholding knowledge in organizations. Second, by delineating specific...

  13. Employee Share Option Scheme And Employees’ Motivation

    Directory of Open Access Journals (Sweden)

    Rebecca Yew Ming Yian

    2011-06-01

    Full Text Available Employee stock options scheme (ESOS is a call option on the ordinary share of a company, issued as a form of non-cash compensation or as an incentive tool. ESOS gives an employee the right to buy shares at a fixed price for a defined number of years into the future. The trend toward broad-based share options may come to an end as companies are scaling back due to the changes in accounting standards. Similarly, companies in Malaysia, especially in the banking industry which originally offered share options to their employees are now pulling back this scheme. Does the movement to scale back share options affect employees’ motivation? This is an empirical question which this paper intends to explore. It is hope that the commercial banks will reconsider offering ESOS in rewarding their employees if the research finding indicates that it plays a significant role in motivating employees.

  14. Performing an allreduce operation using shared memory

    Science.gov (United States)

    Archer, Charles J [Rochester, MN; Dozsa, Gabor [Ardsley, NY; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

    2012-04-17

    Methods, apparatus, and products are disclosed for performing an allreduce operation using shared memory that include: receiving, by at least one of a plurality of processing cores on a compute node, an instruction to perform an allreduce operation; establishing, by the core that received the instruction, a job status object for specifying a plurality of shared memory allreduce work units, the plurality of shared memory allreduce work units together performing the allreduce operation on the compute node; determining, by an available core on the compute node, a next shared memory allreduce work unit in the job status object; and performing, by that available core on the compute node, that next shared memory allreduce work unit.

  15. Meromorphic functions sharing one value by weight

    Institute of Scientific and Technical Information of China (English)

    LAI Li-ping; LI Chun-hong

    2007-01-01

    The uniqueness of meromorphic fuctions sharing one value was studied.Using the concept of weighted sharing,we proved the following theorem.For two meromorphic functions f and g which are not polynominals of degree less than a positive integer k, if.fnf(k) and gng(k) share(1,2),where n is another positive integer not less than k+10,then fnf(k) identically equals gng(k) or fnf(k)gng(k) identically equals 1.Particularly for k=1,we improved the results of Yang[Yang CC,Hua XH,Uniqueness and value-sharing of meromorphic functions,Annales Academi(ae) Scientiarum Fennic(ae) Mathematica,1997,22:395-406],and Fang[Fang ML,Hua XH,Entire function that share one value,Joumal of Nanjing University,1996,13(1):44-48.(In Chinese)].

  16. Peer-to-Peer Service Sharing Platforms

    DEFF Research Database (Denmark)

    Andersson, Magnus; Hjalmarsson, Anders; Avital, Michel

    2013-01-01

    The sharing economy has been growing continuously in the last decade thanks to the proliferation of internet-based platforms that allow people to disintermediate the traditional commercial channels and to share excess resources and trade with one another effectively at a reasonably low transaction...... cost. Whereas early peer-to-peer platforms were designed to enable file sharing and goods trading, we recently witness the emergence of a new breed of peer-to-peer platforms that are designed for ordinary service sharing. Ordinary services entail intangible provisions and are defined as an economic...... activity that generates immaterial benefits and does not result in ownership of material goods. Based on a structured analysis of 41 internet-based rideshare platforms, we explore and layout the unique characteristics of peer-to-peer service sharing platforms based on three distinct temporal patterns...

  17. How to Split a Shared Secret into Shared Bits in Constant-Round

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Fitzi, Matthias; Nielsen, Jesper Buus

    We show that if a set of players hold shares of a value $a\\in Z_p$ for some prime $p$ (where the set of shares is written $[a]_p$), it is possible to compute, in constant round and with unconditional security, sharings of the bits of $a$, i.e.~compute sharings $[a_0]_p, \\ldots, [a_{l-1}]_p...

  18. Sharing and helping: predictors of adolescents' willingness to share diabetes personal health information with peers.

    Science.gov (United States)

    Vaala, Sarah E; Lee, Joyce M; Hood, Korey K; Mulvaney, Shelagh A

    2017-05-29

    Sharing personal information about type 1 diabetes (T1D) can help adolescents obtain social support, enhance social learning, and improve self-care. Diabetes technologies, online communities, and health interventions increasingly feature data-sharing components. This study examines factors underlying adolescents' willingness to share personal T1D information with peers. Participants were 134 adolescents (12-17 years of age; 56% female) who completed an online survey regarding experiences helping others with T1D, perceived social resources, beliefs about the value of sharing information and helping others, and willingness to share T1D information. Hemoglobin A1c values were obtained from medical records. Adolescents were more willing to share how they accomplished T1D tasks than how often they completed them, and least willing to share glucose control status. In multivariate analyses, sharing/helping beliefs (β = 0.26, P  value; β = -0.26, P  personal health information. Glucose control moderated relationships such that adolescents with worse A1c values had stronger relationships between sharing/helping beliefs and willingness to share (β = 0.18, P  personal health information, particularly if they have better diabetes health status and a stronger belief in the benefits of sharing. Social learning and social media components may improve intervention participation, engagement, and outcomes by boosting adolescents' beliefs about the benefits of sharing information and helping others.

  19. The Open Faculty: To Share or Not to Share--Is That the Question?

    Science.gov (United States)

    Andersen, Maria H.

    2010-01-01

    In this article, the author shares her view of "open faculty." To truly understand "open faculty," one needs to step back to a time before the Internet, before it was so easy and inexpensive to share anything and everything. In the pre-Internet era, faculty fell on the same continuum between those who freely share ideas and resources and those who…

  20. Minisequencing mitochondrial DNA pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Carracedo Ángel

    2008-04-01

    Full Text Available Abstract Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain patients carrying haplogroup J lineages (Fisher's Exact test, P-value Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories.

  1. HNPCC: Six new pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Epplen Joerg T

    2004-06-01

    Full Text Available Abstract Background Hereditary non-polyposis colorectal cancer (HNPCC is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR. HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in the DNA mismatch-repair genes MLH1, MSH2 and MSH6. Methods Patients with clinical diagnosis of HNPCC were counselled. Tumor specimen were analysed for microsatellite instability and immunohistochemistry for MLH1, MSH2 and MSH6 protein was performed. If one of these proteins was not detectable in the tumor mutation analysis of the corresponding gene was carried out. Results We identified 6 frameshift mutations (2 in MLH1, 3 in MSH2, 1 in MSH6 resulting in a premature stop: two mutations in MLH1 (c.2198_2199insAACA [p.N733fsX745], c.2076_2077delTG [p.G693fsX702], three mutations in MSH2 (c.810_811delGT [p.C271fsX282], c.763_766delAGTGinsTT [p.F255fsX282], c.873_876delGACT [p.L292fsX298] and one mutation in MSH6 (c.1421_1422dupTG [p.C475fsX480]. All six tumors tested for microsatellite instability showed high levels of microsatellite instability (MSI-H. Conclusions HNPCC in families with MSH6 germline mutations may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations.

  2. Radiation mutation breeding

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hi Sup; Kim, Jae Sung; Kim, Jin Kyu; Shin, In Chul; Lim, Young Taek

    1998-04-01

    In order to develop an advanced technical knowledge for the selection of better mutants, some of the crops were irradiated and the mutation rate, the survival rate and the method for selction of a mutant were studied. Furthermore, this study aimed to obtain basic data applicable to the development of genetic resources by evaluation and analysis the specific character for selection of the superior mutant and its plant breeding. 1. selection of the mutant with a superior resistance against environment in the principal crops 1) New varieties of mutant rices such as Wonpyeongbyeo, Wongwangbyeo, Winmibyeo, and heogseon chalbeyeo (sticky forma) were registered in the national variety list and made an application to crop variety protection right. They are under review now. 2) We also keep on studying on the number of a grain of 8 lines of excellent mutant rice for the purpose of improvement of breeding . 3) We selected 3 lines which have a resistance to pod and stem blight in large soybean, 31 lines with small grain size and higher yield, 112 lines of soybean of cooking, 7 lines of low lipoxygenase content, and 12 lines with decreased phytic acid content by 20 % compared to the previous level. 2. Selection of advanced Mugunwha (Rose of Sharon) mutant 1) Bagseul, a new variety of mutant, was developed and 30 plantlets of it are being proliferated. 2) Fifty-three lines of a mutant having a various morphologies were selected.

  3. BRAF Mutation Is Rare in Advanced-Stage Low-Grade Ovarian Serous Carcinomas

    Science.gov (United States)

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Deavers, Michael T.; Mok, Samuel C.; Zu, Zhifei; Sun, Charlotte; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.

    2010-01-01

    Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. PMID:20802181

  4. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.

    Science.gov (United States)

    Lim, Weng Khong; Ong, Choon Kiat; Tan, Jing; Thike, Aye Aye; Ng, Cedric Chuan Young; Rajasegaran, Vikneswari; Myint, Swe Swe; Nagarajan, Sanjanaa; Nasir, Nur Diyana Md; McPherson, John R; Cutcutache, Ioana; Poore, Gregory; Tay, Su Ting; Ooi, Wei Siong; Tan, Veronique Kiak Mien; Hartman, Mikael; Ong, Kong Wee; Tan, Benita K T; Rozen, Steven G; Tan, Puay Hoon; Tan, Patrick; Teh, Bin Tean

    2014-08-01

    Fibroadenomas are the most common breast tumors in women under 30 (refs. 1,2). Exome sequencing of eight fibroadenomas with matching whole-blood samples revealed recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit. Targeted sequencing of an additional 90 fibroadenomas confirmed highly frequent MED12 exon 2 mutations (58/98, 59%) that are probably somatic, with 71% of mutations occurring in codon 44. Using laser capture microdissection, we show that MED12 fibroadenoma mutations are present in stromal but not epithelial mammary cells. Expression profiling of MED12-mutated and wild-type fibroadenomas revealed that MED12 mutations are associated with dysregulated estrogen signaling and extracellular matrix organization. The fibroadenoma MED12 mutation spectrum is nearly identical to that of previously reported MED12 lesions in uterine leiomyoma but not those of other tumors. Benign tumors of the breast and uterus, both of which are key target tissues of estrogen, may thus share a common genetic basis underpinned by highly frequent and specific MED12 mutations.

  5. A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

    Directory of Open Access Journals (Sweden)

    Escámez María-José

    2010-09-01

    Full Text Available Abstract Background Recessive Dystrophic Epidermolysis Bullosa (RDEB is a genodermatosis caused by more than 500 different mutations in the COL7A1 gene and characterized by blistering of the skin following a minimal friction or mechanical trauma. The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation. Methods Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs throughout the COL7A1 gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin. Results Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation. Conclusion Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (CCGCTCAAA_6527insC, thus suggesting the presence of a common ancestor.

  6. Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

    Science.gov (United States)

    Thiffault, Isabelle; Wolf, Nicole I.; Forget, Diane; Guerrero, Kether; Tran, Luan T.; Choquet, Karine; Lavallée-Adam, Mathieu; Poitras, Christian; Brais, Bernard; Yoon, Grace; Sztriha, Laszlo; Webster, Richard I.; Timmann, Dagmar; van de Warrenburg, Bart P.; Seeger, Jürgen; Zimmermann, Alíz; Máté, Adrienn; Goizet, Cyril; Fung, Eva; van der Knaap, Marjo S.; Fribourg, Sébastien; Vanderver, Adeline; Simons, Cas; Taft, Ryan J.; Yates III, John R.; Coulombe, Benoit; Bernard, Geneviève

    2015-01-01

    A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy. PMID:26151409

  7. Mutations induced by ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Pfeifer, Gerd P. [Department of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States)]. E-mail: gpfeifer@coh.org; You, Young-Hyun [Department of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States); Besaratinia, Ahmad [Department of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States)

    2005-04-01

    The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms

  8. Neurochemistry changes associated with mutations in familial Parkinson's disease.

    Science.gov (United States)

    Siddique, M M; Tan, E K

    2010-01-01

    Parkinson's disease (PD), a common neurodegenerative disease, is characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. The exact role of genetic and environmental factors in the pathogenesis of PD has frequently been debated. The association of MPTP (methyl-4-phenyl-1, 2, 3, 6- tetrahydropyridine) and toxins (such as rotenone) with parkinsonism highlights the potential etiologic role of environmental toxins in disease causation. The recent discoveries of monogenic (such as α-synuclein, Parkin, UCHL1, PINK1, DJ-1, LRRK2) forms of PD have provided considerable insights into its pathophysiology. Parkin, an ubiquitin protein ligase assists in the degradation of toxic substrates via the ubiquitin proteasome system. It can also mediate a nondegradative form of ubiquitination. PINK1 and LRRK2 are possibly involved in the phosphorylation of substrates important for various cellular functions. Some toxins could interact with α-synuclein, an endogenous protein that is implicated in pathology of PD. Increasing in vitro and in vivo studies suggest that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system dysfunction underpin the pathogenesis of sporadic and familial forms of PD. Elucidation of the functions of the proteins encoded by the diseasecausing genes will provide an opportunity for identification of specific pathways that could be targeted in neurotherapeutics.

  9. Secret Sharing of a Quantum State.

    Science.gov (United States)

    Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

    2016-07-15

    Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

  10. Shared governance in a clinic system.

    Science.gov (United States)

    Meyers, Michelle M; Costanzo, Cindy

    2015-01-01

    Shared governance in health care empowers nurses to share in the decision-making process, which results in decentralized management and collective accountability. Share governance practices have been present in hospitals since the late 1970s. However, shared governance in ambulatory care clinics has not been well established. The subjects of this quality project included staff and administrative nurses in a clinic system. The stakeholder committee chose what model of shared governance to implement and educated clinic staff. The Index of Professional Nursing Governance measured a shared governance score pre- and postimplementation of the Clinic Nursing Council. The Clinic Nursing Council met bimonthly for 3 months during this project to discuss issues and make decisions related to nursing staff. The Index of Professional Nursing Governance scores indicated traditional governance pre- and postimplementation of the Clinic Nursing Council, which is to be expected. The stakeholder committee was beneficial to the initial implementation process and facilitated staff nurse involvement. Shared governance is an evolutionary process that develops empowered nurses and nurse leaders.

  11. Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma

    Directory of Open Access Journals (Sweden)

    Bardeesy Nabeel

    2011-02-01

    Full Text Available Abstract Background The genetics of advanced biliary tract cancers (BTC, which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%. KRAS mutations were identified in 3 (13% intra-hepatic cholangiocarcinomas and 1 (33% perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.

  12. Optimal Risk Sharing under Distorted Probabilities

    CERN Document Server

    Ludkovski, M

    2008-01-01

    We study optimal risk sharing among $n$ agents endowed with distortion risk measures. Our model includes market frictions that can either represent linear transaction costs or risk premia charged by a clearing house for the agents. Risk sharing under third-party constraints is also considered. We obtain an explicit formula for Pareto optimal allocations. In particular, we find that a stop-loss or deductible risk sharing is optimal in the case of two agents and several common distortion functions. This extends recent result of Jouini et al. (2006) to the problem with unbounded risks and market frictions.

  13. Shared governance in the endoscopy department.

    Science.gov (United States)

    Metcalf, R; Tate, R

    1995-01-01

    Studies have indicated that active participation by employees improves job satisfaction and performance. There is a sense of pride and accountability that is demonstrated in the work environment when staff are involved in the decision-making process. Recent emergence of a relatively new philosophy for management that promotes employee ownership is shared governance. This type of leadership allows individuals who are at the center of the work place to participate in the decisions that actively reflect their needs. In this article, the authors describe the process of implementing shared governance in an Endoscopy Department. The effectiveness of shared governance is evidenced by the renewed enthusiasm and energy demonstrated by the staff.

  14. Share Contract Choices and Economic Performance

    DEFF Research Database (Denmark)

    Salazar Espinoza, César Antonio

    2015-01-01

    Typically, crew members in fisheries are remunerated through a share of the total revenues. However, there is little empirical evidence on the mechanisms by which revenues are distributed to labor and capital, and how these distributions affect economic performance. Under an agency problem...... framework, we estimate a dose-response function to study the formation of contracts and identify the marginal effects of changes in crew profit shares on fishing returns in Chilean artisanal fisheries. The results support share contract choices based on bargaining power, monitoring costs, technology, state...

  15. Sharing Your Knowledge: Getting Your Idea Published.

    Science.gov (United States)

    Milner, Kerry A

    2016-01-01

    Nurses have a professional and ethical obligation to share best practices to advance nursing knowledge and create better outcomes for patients. Practice-based evidence is as important to advancing evidence-based practice as original research. Infusion nurses are in an excellent position to share local best practices more broadly. Writing for publication is a mechanism for disseminating practice-based evidence. This article reviews the importance of sharing best practices and describes not only how to prepare a manuscript for publication but also resources that will help nurses in this important endeavor.

  16. Describing functional requirements for knowledge sharing communities

    Science.gov (United States)

    Garrett, Sandra; Caldwell, Barrett

    2002-01-01

    Human collaboration in distributed knowledge sharing groups depends on the functionality of information and communication technologies (ICT) to support performance. Since many of these dynamic environments are constrained by time limits, knowledge must be shared efficiently by adapting the level of information detail to the specific situation. This paper focuses on the process of knowledge and context sharing with and without mediation by ICT, as well as issues to be resolved when determining appropriate ICT channels. Both technology-rich and non-technology examples are discussed.

  17. Shared address collectives using counter mechanisms

    Science.gov (United States)

    Blocksome, Michael; Dozsa, Gabor; Gooding, Thomas M; Heidelberger, Philip; Kumar, Sameer; Mamidala, Amith R; Miller, Douglas

    2014-02-18

    A shared address space on a compute node stores data received from a network and data to transmit to the network. The shared address space includes an application buffer that can be directly operated upon by a plurality of processes, for instance, running on different cores on the compute node. A shared counter is used for one or more of signaling arrival of the data across the plurality of processes running on the compute node, signaling completion of an operation performed by one or more of the plurality of processes, obtaining reservation slots by one or more of the plurality of processes, or combinations thereof.

  18. Global games with noisy sharing of information

    KAUST Repository

    Touri, Behrouz

    2014-12-15

    We provide a framework for the study of global games with noisy sharing of information. In contrast to the previous works where it is shown that an intuitive threshold policy is an equilibrium for such games, we show that noisy sharing of information leads to non-existence of such an equilibrium. We also investigate the group best-response dynamics of two groups of agents sharing the same information to threshold policies based on each group\\'s observation and show the convergence of such dynamics.

  19. SharePoint 2010 Enterprise Architect's Guidebook

    CERN Document Server

    Wilson, Brian; Baer, Bill; Kearn, Martin; Shah, Arpan; Adams, Jim; Bridport, Nigel; Esperanca, Huge; Gideon, Chris; Hassani, Sam; Hodgkinson, Neil; Juvonen, Vesa; Kleven, Scott; Morrish, Ian; Olenick, Paul; Ranlett, Matt; Voskresenskaya, Natalya; Walker, Simon; Whitehead, Chris

    2012-01-01

    Tips and techniques for becoming a successful SharePoint architect If you're eager to design and architect a successful deployment of SharePoint 2010, then this is the book for you. Packed with real-world experiences and solid processes, this guidebook provides you with everything you need to perform for designing and architecting enterprise portal services. Helpful examples examine the common design issues affecting SharePoint 2010 environments that can cause deployments to fail so you can learn what to avoid. Plus, key development and deployment issues are covered from an architecture perspe

  20. Markov models for accumulating mutations

    CERN Document Server

    Beerenwinkel, Niko

    2007-01-01

    We introduce and analyze a waiting time model for the accumulation of genetic changes. The continuous time conjunctive Bayesian network is defined by a partially ordered set of mutations and by the rate of fixation of each mutation. The partial order encodes constraints on the order in which mutations can fixate in the population, shedding light on the mutational pathways underlying the evolutionary process. We study a censored version of the model and derive equations for an EM algorithm to perform maximum likelihood estimation of the model parameters. We also show how to select the maximum likelihood poset. The model is applied to genetic data from different cancers and from drug resistant HIV samples, indicating implications for diagnosis and treatment.

  1. Dynamical Mutation of Dark Energy

    CERN Document Server

    Abramo, L R; Liberato, L; Rosenfeld, R

    2007-01-01

    We discuss the intriguing possibility that dark energy may change its equation of state in situations where large dark energy fluctuations are present. We show indications of this dynamical mutation in some generic models of dark energy.

  2. PPARγ mutations, lipodystrophy and diabetes.

    Science.gov (United States)

    Astapova, Olga; Leff, Todd

    2014-11-01

    The focus of this review is the lipodystrophy syndrome caused by mutation in the PPARγ nuclear receptor - partial familial lipodystrophy FPLD3. To provide a broader context for how these mutations act to generate the clinical features of partial lipodystrophy we will review the basic biology of PPARγ and also survey the set PPARγ genetic variants that do not cause lipodystrophy, but are nonetheless associated with clinically related syndromes, specifically type 2 diabetes.

  3. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  4. Mutation Analysis Identifies GUCY2D as the Major Gene Responsible for Autosomal Dominant Progressive Cone Degeneration

    Science.gov (United States)

    Kitiratschky, Veronique B. D.; Wilke, Robert; Renner, Agnes B.; Kellner, Ulrich; Vadalà, Maria; Birch, David G.; Wissinger, Bernd; Zrenner, Eberhart; Kohl, Susanne

    2017-01-01

    Purpose Heterozygous mutations in the GUCY2D gene, which encodes the membrane-bound retinal guanylyl cyclase-1 protein (RetGC-1), have been shown to cause autosomal dominant inherited cone degeneration and cone–rod degeneration (adCD, adCRD). The present study was a comprehensive screening of the GUCY2D gene in 27 adCD and adCRD unrelated families of these rare disorders. Methods Mutation analysis was performed by direct sequencing as well as PCR and subsequent restriction length polymorphism analysis (PCR/RFLP). Haplotype analysis was performed in selected patients by using microsatellite markers. Results GUCY2D gene mutations were identified in 11 (40%) of 27 patients, and all mutations clustered to codon 838, including two known and one novel missense mutation: p.R838C, p.R838H, and p.R838G. Haplotype analysis showed that among the studied patients only two of the six analyzed p.R838C mutation carriers shared a common haplotype and that none of the p.R838H mutation carriers did. Conclusions GUCY2D is a major gene responsible for progressive autosomal dominant cone degeneration. All identified mutations localize to codon 838. Haplotype analysis indicates that in most cases these mutations arise independently. Thus, codon 838 is likely to be a mutation hotspot in the GUCY2D gene. PMID:18487367

  5. Mutations causative of familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Benn, Marianne; Watts, Gerald F; Tybjærg-Hansen, Anne

    2016-01-01

    AIMS: Ideally, familial hypercholesterolaemia (FH) is diagnosed by testing for mutations that decrease the catabolism of low-density lipoprotein (LDL) cholesterol; however, genetic testing is not universally available. The aim of the present study was to assess the frequency and predictors of FH....... The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH......-cholesterol concentration to discriminate between mutation carriers and non-carriers was 4.4 mmol/L. CONCLUSION: Familial hypercholesterolaemia-causing mutations are estimated to occur in 1:217 in the general population and are best identified by a definite or probable phenotypic diagnosis of FH based on the DLCN criteria...

  6. Team learning: building shared mental models

    NARCIS (Netherlands)

    Van den Bossche, Piet; Gijselaers, Wim; Segers, Mien; Woltjers, Geert; Kirschner, Paul A.

    2011-01-01

    Van den Bossche, P., Gijselaers, W., Segers, M., Woltjer, G., & Kirschner, P. A. (2011). Team learning: Building shared mental models. Instructional Science, 39, 283-301. doi:10.1007/s11251-010-9128-3.

  7. Sharing personal knowlege over the Semantic Web

    NARCIS (Netherlands)

    Kostadinov, Zlatko

    2006-01-01

    Please, cite this publication as: Kostadinov, Z. (2006). Sharing personal knowlege over the Semantic Web. Proceedings of International Workshop in Learning Networks for Lifelong Competence Development, TENCompetence Conference. September 12th, Sofia, Bulgaria: TENCompetence. Retrieved June 30th, 200

  8. Information Flow in Secret Sharing Protocols

    CERN Document Server

    Kashefi, Elham; Mhalla, Mehdi; Perdrix, Simon

    2009-01-01

    The entangled graph states have emerged as an elegant and powerful quantum resource, indeed almost all multiparty protocols can be written in terms of graph states including measurement based quantum computation (MBQC), error correction and secret sharing amongst others. In addition they are at the forefront in terms of implementations. As such they represent an excellent opportunity to move towards integrated protocols involving many of these elements. In this paper we look at expressing and extending graph state secret sharing and MBQC in a common framework and graphical language related to flow. We do so with two main contributions. First we express in entirely graphical terms which set of players can access which information in graph state secret sharing protocols. These succinct graphical descriptions of access allow us to take known results from graph theory to make statements on the generalisation of the previous schemes to present new secret sharing protocols. Second, we give a set of necessary condit...

  9. Sharing personal knowlege over the Semantic Web

    NARCIS (Netherlands)

    Kostadinov, Zlatko

    2006-01-01

    Please, cite this publication as: Kostadinov, Z. (2006). Sharing personal knowlege over the Semantic Web. Proceedings of International Workshop in Learning Networks for Lifelong Competence Development, TENCompetence Conference. September 12th, Sofia, Bulgaria: TENCompetence. Retrieved June 30th,

  10. Shared services as a new organizational form

    NARCIS (Netherlands)

    Bondarouk, Tanya; Bondarouk, Tanya

    2014-01-01

    Organizations increasingly establish Shared Service Centers, either for transactional (administrative) or transformational (organizational change) purposes. Their popularity originates from a combination of efficiency gains and an increase in service quality, without giving up control of the organiz

  11. Stimulating Personal Development and Knowledge Sharing

    NARCIS (Netherlands)

    Koper, Rob; Stefanov, Krassen; Dicheva, Darina

    2009-01-01

    Koper, R., Stefanov, K., & Dicheva, D. (Eds.) (2009). Proceedings of the 5th International TENCompetence Open Workshop "Stimulating Personal Development and Knowledge Sharing". October, 30-31, 2008, Sofia, Bulgaria: TENCompetence Workshop.

  12. Stimulating Personal Development and Knowledge Sharing

    NARCIS (Netherlands)

    Koper, Rob; Stefanov, Krassen; Dicheva, Darina

    2009-01-01

    Koper, R., Stefanov, K., & Dicheva, D. (Eds.) (2009). Proceedings of the 5th International TENCompetence Open Workshop "Stimulating Personal Development and Knowledge Sharing". October, 30-31, 2008, Sofia, Bulgaria: TENCompetence Workshop.

  13. Statistical Uncertainty in the Medicare Shared Savings...

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to analysis reported in Statistical Uncertainty in the Medicare Shared Savings Program published in Volume 2, Issue 4 of the Medicare and Medicaid Research...

  14. Contract-Based Cooperative Spectrum Sharing

    CERN Document Server

    Duan, Lingjie; Huang, Jianwei

    2011-01-01

    Providing proper economic incentives is essential for the success of dynamic spectrum sharing. Cooperative spectrum sharing is one effective way to achieve this goal. In cooperative spectrum sharing, secondary users (SUs) relay traffics for primary users (PUs), in exchange for dedicated transmission time for the SUs' own communication needs. In this paper, we study the cooperative spectrum sharing under incomplete information, where SUs' types (capturing their heterogeneity in relay channel gains and evaluations of power consumptions) are private information and not known by PUs. Inspired by the contract theory, we model the network as a labor market. The single PU is the employer who offers a contract to the SUs. The contract consists of a set of contract items representing combinations of spectrum accessing time (i.e., reward) and relaying power (i.e., contribution). The SUs are employees, and each of them selects the best contract item to maximize his payoff. We study the optimal contract design for both w...

  15. Sharing Knowledge in Adaptive Learning Systems

    NARCIS (Netherlands)

    Kravcik, Milos; Gasevic, Dragan

    2006-01-01

    Please, cite this publication as: Kravcik, M. & Gasevic, D. (2006). Sharing Knowledge in Adaptive Learning Systems. Proceedings of ICALT2006. July, Kerkrade, The Netherlands: IEEE. Retrieved July 30th, 2006, from http://dspace.learningnetworks.org

  16. Quantum secret sharing with minimized quantum communication

    Science.gov (United States)

    Fortescue, Ben; Gour, Gilad

    2013-03-01

    Standard techniques for sharing a quantum secret among multiple players (such that certain subsets of the players can recover the secret while others are denied all knowledge of the secret) require a large amount of quantum communication to distribute the secret, which is likely to be the most costly resource in any practical scheme. Two known methods for reducing this cost are the use of imperfect ``ramp'' secret sharing (in which security is sacrificed for efficiency) and classical encryption (in which certain elements of the players' shares consist of classical information only). We demonstrate how one may combine these methods to reduce the required quantum communication below what has been previously achieved, in some cases to a provable minimum, without any loss of security. The techniques involved are closely-related to the properties of stabilizer codes, and thus have strong potential for being adapted to a wide range of quantum secret sharing schemes.

  17. Labelling : Security in Information Management and Sharing

    NARCIS (Netherlands)

    Schotanus, H.A.; Hartog, T.; Hut, D.H.; Boonstra, D.

    2011-01-01

    Military communication infrastructures are often deployed as stand-alone information systems operating at the System High mode. Network-Enabled Capabilities (NEC) and combined military operations lead to new requirements for information management and sharing which current communication architecture

  18. Shared Enterprise Geodata and Services (SEGS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The core mission of Shared Enterprise Geodata and Services (SEGS) is to provide a single point of ownership for geospatial datasets that are national in extent and...

  19. Company Profile Shandong Luyang Share Co. Ltd

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Shandong Luyang Share Co. Ltd, established in 1984, after more than double decades' struggle and effort, has been developed to be the biggest professional manufacturer of ceramic fiber products in Asia.

  20. How to foster sharing of educational resources?

    NARCIS (Netherlands)

    Van der Baaren, John; De Vries, Fred

    2011-01-01

    Van der Baaren, J., & De Vries, F. (2010). How to foster sharing of educational resources? Paper presented at the OPENED conference. November, 2-4, 2010, Barcelona, Spain, UOC, OU, BYU.

  1. Optimal Reinsurance: A Risk Sharing Approach

    Directory of Open Access Journals (Sweden)

    Alejandro Balbas

    2013-08-01

    Full Text Available This paper proposes risk sharing strategies, which allow insurers to cooperate and diversify non-systemic risk. We deal with both deviation measures and coherent risk measures and provide general mathematical methods applying to optimize them all. Numerical examples are given in order to illustrate how efficiently the non-systemic risk can be diversified and how effective the presented mathematical tools may be. It is also illustrated how the existence of huge disasters may lead to wrong solutions of our optimal risk sharing problem, in the sense that the involved risk measure could ignore the existence of a non-null probability of "global ruin" after the design of the optimal risk sharing strategy. To overcome this caveat, one can use more conservative risk measures. The stability in the large of the optimal sharing plan guarantees that "the global ruin caveat" may be also addressed and solved with the presented methods.

  2. Kwaabana: File sharing for rural networks

    CSIR Research Space (South Africa)

    Johnson, DL

    2013-12-01

    Full Text Available As usage of online social networks and social media continues to experience exponential growth, the amount of data being shared between users is increasing without bound. While this has revolutionized communication for many Internet users, users...

  3. Novel energy sharing collisions of multicomponent solitons

    Indian Academy of Sciences (India)

    T Kanna; K Sakkaravarthi; M Vijayajayanthi

    2015-11-01

    In this paper, we discuss the fascinating energy sharing collisions of multicomponent solitons in certain incoherently coupled and coherently coupled nonlinear Schrödinger-type equations arising in the context of nonlinear optics.

  4. Benefit sharing: it's time for a definition.

    Science.gov (United States)

    Schroeder, D

    2007-04-01

    Benefit sharing has been a recurrent theme in international debates for the past two decades. However, despite its prominence in law, medical ethics and political philosophy, the concept has never been satisfactorily defined. In this conceptual paper, a definition that combines current legal guidelines with input from ethics debates is developed. Philosophers like boxes; protective casings into which they can put concisely-defined concepts. Autonomy is the human capacity for self-determination; beneficence denotes the virtue of good deeds, coercion is the intentional threat of harm and so on. What about benefit sharing? Does the concept have a box and are the contents clearly defined? The answer to this question has to be no. The concept of benefit sharing is almost unique in that various disciplines use it regularly without precise definitions. In this article, a definition for benefit sharing is provided, to eliminate unnecessary ambiguity.

  5. 50 CFR 80.12 - Cost sharing.

    Science.gov (United States)

    2010-10-01

    ...) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE REQUIREMENTS, PITTMAN-ROBERTSON WILDLIFE RESTORATION AND DINGELL-JOHNSON SPORT FISH RESTORATION ACTS § 80.12 Cost sharing. Federal...

  6. Science: the shared language of development

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    This year’s conference on “Sharing Knowledge across the Mediterranean” is being held in Malta from 5 to 8 May. It is the sixth in a series of conferences whose aim is to promote dialogue among countries in the Mediterranean region through the language of science, organised by the “Sharing Knowledge Foundation”. CERN is one of the Foundation’s partners, and today John Ellis, one of CERN’s non-Member State advisors, announced CERN's readiness to donate several hundred computers to various Moroccan universities to encourage their participation in high-energy physics and Grid computing   CERN scientists, including John Ellis and Patrick Fassnacht, participate in the 6th Sharing Knowledge across the Mediterranean conference in Malta, on Friday 6 May. This gesture of support to the North African region was announced during the sixth "Sharing Knowledge across the Mediterranean" conference. Embracing many of CERN's gu...

  7. Availability Cascades and the Sharing Economy

    DEFF Research Database (Denmark)

    Netter, Sarah

    2016-01-01

    As scholars search for a new concept that will provide answers on how modern societies should make sense of and resolve the social and environmental problems linked to our modes of production and consumption, the sharing economy is attracting increased attention. To better understand this emergent...... focus on a sharing economy and associated business and consumption models, this conceptual chapter applies cascade theory to some of the most pronounced narratives , suggesting a win-win scenario, especially as they relate to the claim of sustainability. Given academics, practitioners, and civil society......’s shared history of (too) rapidly embracing new concepts that enable both business opportunities and a clear conscience, this chapter proposes that the implications of the sharing economy should be critically explored before it is actively promoted as the latest best fix....

  8. SharePoint无处不在

    Institute of Scientific and Technical Information of China (English)

    Jeff James; 黄思维(译)

    2009-01-01

    和微软的那些日渐丧失优势和地盘的产品不同,SharePoint在企业协作工具市场上长期占据着统治地位,并且增长势头良好。那么。SharePoint成功的秘密是什么?

  9. SharePoint解决方案

    Institute of Scientific and Technical Information of China (English)

    Ethan; Wilansky; Jeff; Sandier; 刘海蜀(译)

    2006-01-01

    本文继续讨论关于SharePoint产品本身的缺陷——项目级安全性设置的问题。作者独创性地将文件夹权限管理的精神,应用在SharePoint产品上,希望能够对读者具有一定的启发作用。

  10. Knowledge sharing: a management control perspective.

    OpenAIRE

    Haesebrouck, Katlijn

    2016-01-01

    The uniqueness of a firm’s knowledge plays a fundamental role in its sustained competitive advantage, economic growth and corporate value, but developing knowledge as an organizational asset requires employees to actively and correctly share their knowledge. Nevertheless, the transfer of knowledge within organizations is often limited in practice. This dissertation investigates via three experimental papers how management control systems can stimulate knowledge sharing. In particular, we stud...

  11. Shared language:Towards more effective communication.

    Science.gov (United States)

    Thomas, Joyce; McDonagh, Deana

    2013-01-01

    The ability to communicate to others and express ourselves is a basic human need. As we develop our understanding of the world, based on our upbringing, education and so on, our perspective and the way we communicate can differ from those around us. Engaging and interacting with others is a critical part of healthy living. It is the responsibility of the individual to ensure that they are understood in the way they intended.Shared language refers to people developing understanding amongst themselves based on language (e.g. spoken, text) to help them communicate more effectively. The key to understanding language is to first notice and be mindful of your language. Developing a shared language is an ongoing process that requires intention and time, which results in better understanding.Shared language is critical to collaboration, and collaboration is critical to business and education. With whom and how many people do you connect? Your 'shared language' makes a difference in the world. So, how do we successfully do this? This paper shares several strategies.Your sphere of influence will carry forward what and how you are communicating. Developing and nurturing a shared language is an essential element to enhance communication and collaboration whether it is simply between partners or across the larger community of business and customers. Constant awareness and education is required to maintain the shared language. We are living in an increasingly smaller global community. Business is built on relationships. If you invest in developing shared language, your relationships and your business will thrive.

  12. Towards a Theory of Socially Shared Consumption

    OpenAIRE

    Kunst, Katrine; Vatrapu, Ravi

    2014-01-01

    Recent years have seen an increased sharing of consumptive practices, experiences and evaluations on social media platforms. Such socially shared consumption can range from electronic word-of-mouth to formal online reviews as well as automated product mentions facilitated by social media applications Based on a review of extant emerging literature on this topic as well as of literature on relevant topics such as social influence, online reviews, theories of the extended self and conspicuous c...

  13. Shared language:Towards more effective communication

    Directory of Open Access Journals (Sweden)

    Joyce Thomas

    2013-01-01

    Full Text Available The ability to communicate to others and express ourselves is a basic human need. As we develop our understanding of the world, based on our upbringing, education and so on, our perspective and the way we communicate can differ from those around us. Engaging and interacting with others is a critical part of healthy living. It is the responsibility of the individual to ensure that they are understood in the way they intended.Shared language refers to people developing understanding amongst themselves based on language (e.g. spoken, text to help them communicate more effectively. The key to understanding language is to first notice and be mindful of your language. Developing a shared language is an ongoing process that requires intention and time, which results in better understanding.Shared language is critical to collaboration, and collaboration is critical to business and education. With whom and how many people do you connect? Your 'shared language' makes a difference in the world. So, how do we successfully do this? This paper shares several strategies.Your sphere of influence will carry forward what and how you are communicating. Developing and nurturing a shared language is an essential element to enhance communication and collaboration whether it is simply between partners or across the larger community of business and customers. Constant awareness and education is required to maintain the shared language. We are living in an increasingly smaller global community. Business is built on relationships. If you invest in developing shared language, your relationships and your business will thrive.

  14. A new scheme for quantum secret sharing

    CERN Document Server

    Bagherinezhad, S; Bagherinezhad, Saber; Karimipour, Vahid

    2002-01-01

    We introduce a protocol for quantum secret sharing based on reusable entangled states. The entangled state between the sender and the receiver acts only as a carrier and no measurement is performed on this shared state. Half of the sequence of bits can be retrieved independently and for the other half the receivers need each other's assistance. We also show that the protocol is completely safe against eavesdropping.

  15. Shared savings gets realtor new water heaters

    Energy Technology Data Exchange (ETDEWEB)

    Mullin, R.

    1983-08-08

    The Grenadier Realty Co. of New York is financing four energy-efficient water heaters for apartment buildings with a shared savings arrangement. The arrangement allows Grenadier to avoid front-end costs, which were paid by Independent Water Heaters Inc. in exchange for a decreasing share of the savings. Grenadier will own the heaters when the five-year contract expires. By allowing a shutdown of boilers during the summer months, the heaters will further increase energy savings. (DCK)

  16. Shared performance monitor in a multiprocessor system

    Science.gov (United States)

    Chiu, George; Gara, Alan G; Salapura, Valentina

    2014-12-02

    A performance monitoring unit (PMU) and method for monitoring performance of events occurring in a multiprocessor system. The multiprocessor system comprises a plurality of processor devices units, each processor device for generating signals representing occurrences of events in the processor device, and, a single shared counter resource for performance monitoring. The performance monitor unit is shared by all processor cores in the multiprocessor system. The PMU is further programmed to monitor event signals issued from non-processor devices.

  17. Effects of Mode Shares on Mode Choice

    OpenAIRE

    Carlos Carrion; Nebiyou Tilahun; David Levinson

    2011-01-01

    This study considers the influence of the knowledge of existing mode shares on travelers mode choice. This contrasts with traditional mode choice models, where the main objective is to predict the overall mode shares as the aggregate of individual mode choices according to variables encompassing attributes of the modes, and characteristics of the travelers. In this study, a computer-administered adaptive stated preference survey is developed and applied to a sample of subjects selected from t...

  18. Data sharing by scientists: Practices and perceptions

    Science.gov (United States)

    Tenopir, C.; Allard, S.; Douglass, K.; Aydinoglu, A.U.; Wu, L.; Read, E.; Manoff, M.; Frame, M.

    2011-01-01

    Background: Scientific research in the 21st century is more data intensive and collaborative than in the past. It is important to study the data practices of researchers - data accessibility, discovery, re-use, preservation and, particularly, data sharing. Data sharing is a valuable part of the scientific method allowing for verification of results and extending research from prior results. Methodology/Principal Findings: A total of 1329 scientists participated in this survey exploring current data sharing practices and perceptions of the barriers and enablers of data sharing. Scientists do not make their data electronically available to others for various reasons, including insufficient time and lack of funding. Most respondents are satisfied with their current processes for the initial and short-term parts of the data or research lifecycle (collecting their research data; searching for, describing or cataloging, analyzing, and short-term storage of their data) but are not satisfied with long-term data preservation. Many organizations do not provide support to their researchers for data management both in the short- and long-term. If certain conditions are met (such as formal citation and sharing reprints) respondents agree they are willing to share their data. There are also significant differences and approaches in data management practices based on primary funding agency, subject discipline, age, work focus, and world region. Conclusions/Significance: Barriers to effective data sharing and preservation are deeply rooted in the practices and culture of the research process as well as the researchers themselves. New mandates for data management plans from NSF and other federal agencies and world-wide attention to the need to share and preserve data could lead to changes. Large scale programs, such as the NSF-sponsored DataNET (including projects like DataONE) will both bring attention and resources to the issue and make it easier for scientists to apply sound

  19. Literature Review on Shared Book Reading

    Institute of Scientific and Technical Information of China (English)

    彭璐

    2013-01-01

    This paper first introduced shared-book reading as good family activity for early childhood. A series of related experi-ments and findings were then examined. The author went on to analyze three influential factors of shared book reading and its de-velopmental, emotional and learning difficulty’s value. Finally, comments and suggestions were made to future researchers of the same field.

  20. Password Sharing and How to Reduce It

    OpenAIRE

    Ferreira, Ana; Correia, Ricardo; Chadwick, David W.; Santos, Henrique; Gomes, Rut; Reis, Diogo; Antunes, Luis

    2010-01-01

    Password sharing is a common security problem. Some application domains are more exposed than others \\ud and, by dealing with very sensitive information, the healthcare domain is definitely not exempt from this \\ud problem. This chapter presents a case study of a cross section of how healthcare professionals actually \\ud deal with password authentication in typical real world scenarios. It then compares the professionals’ \\ud actual practice with what they feel about password sharing and what...

  1. Shared decision-making and patient autonomy.

    Science.gov (United States)

    Sandman, Lars; Munthe, Christian

    2009-01-01

    In patient-centred care, shared decision-making is advocated as the preferred form of medical decision-making. Shared decision-making is supported with reference to patient autonomy without abandoning the patient or giving up the possibility of influencing how the patient is benefited. It is, however, not transparent how shared decision-making is related to autonomy and, in effect, what support autonomy can give shared decision-making. In the article, different forms of shared decision-making are analysed in relation to five different aspects of autonomy: (1) self-realisation; (2) preference satisfaction; (3) self-direction; (4) binary autonomy of the person; (5) gradual autonomy of the person. It is argued that both individually and jointly these aspects will support the models called shared rational deliberative patient choice and joint decision as the preferred versions from an autonomy perspective. Acknowledging that both of these models may fail, the professionally driven best interest compromise model is held out as a satisfactory second-best choice.

  2. THE PERFORMANCE OF SOUTH AFRICAN SHARED SERVICES

    Directory of Open Access Journals (Sweden)

    R.R. Ramphal

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: Many South African companies are adopting the shared services methodology because this structure has led to lower operating costs, greater business efficiency, and improved internal service quality in international companies. Part of a doctoral study on shared services in South African companies shows that their business unit managers have not yet experienced positive rewards from their shared services. This article reports on this study, and suggests a larger-scale research project to validate these findings and to investigate the reasons for the poor performance.

    AFRIKAANSE OPSOMMING: Baie Suid-Afrikaanse maatskappye maak toenemend gebruik van die ‘shared services’- metodologie omdat die struktuur daarvan kan lei tot ʼn afname in operasionele koste, verbeterde besigheidseffektiwiteit, en verhoogde diensgehalte in internasionale maatskappye. ʼn Doktorale studie oor ‘shared services’ in Suid-Afrikaanse maatskappye wys daarop dat individuele besigheidseenheidsbestuurders nie ʼn positiewe belewenis het met ‘shared services’ nie. Hierdie artikel verwys na dié studie, en stel voor dat ʼn meer omvangryke navorsingsprojek onderneem word om die bevindinge te staaf, sowel as om die redes vir swak prestasie te ondersoek.

  3. Factors Associated With Infant Bed-Sharing

    Science.gov (United States)

    Heere, Megan; Moughan, Beth; Alfonsi, Joseph; Rodriguez, Jennifer; Aronoff, Stephen

    2017-01-01

    Objective: Bed-sharing is associated with sudden infant death syndrome and accidental suffocation and strangulation in bed. The purpose of this study was to identify risk factors for newborn bed-sharing. Methods: Postpartum mothers from a university maternity service were contacted by phone to complete a survey. Demographic and environmental data were collected; newborn bed-sharing and sleep environment were self-reported. Results: A total of 1261 mothers completed surveys; bed-sharing was reported by 79 mothers (6.3%). Multivariate logistic regression identified referral to a nurse (odds ratio [OR] = 10; 95% confidence interval [CI] = 4.5-30) and sleep location “other” than a crib, bassinet, or Pack and Play (OR = 7.1; 95% CI = 1.9-25.9) as factors associated with an increased risk of bed-sharing; formula feeding (OR = 0.4; 95% CI = 0.20-0.77) and crib sleeping (OR = 0.49; 95% CI = 0.26-0.86) reduced this risk. Conclusion: Infants with no identifiable places to sleep, significant health issues, and who are breastfed are more likely to bed-share. Interventional studies should be directed at these factors. PMID:28229101

  4. Data sharing, small science and institutional repositories.

    Science.gov (United States)

    Cragin, Melissa H; Palmer, Carole L; Carlson, Jacob R; Witt, Michael

    2010-09-13

    Results are presented from the Data Curation Profiles project research, on who is willing to share what data with whom and when. Emerging from scientists' discussions on sharing are several dimensions suggestive of the variation in both what it means 'to share' and how these processes are carried out. This research indicates that data curation services will need to accommodate a wide range of subdisciplinary data characteristics and sharing practices. As part of a larger set of strategies emerging across academic institutions, institutional repositories (IRs) will contribute to the stewardship and mobilization of scientific research data for e-Research and learning. There will be particular types of data that can be managed well in an IR context when characteristics and practices are well understood. Findings from this study elucidate scientists' views on 'sharable' forms of data-the particular representation that they view as most valued for reuse by others within their own research areas-and the anticipated duration for such reuse. Reported sharing incidents that provide insights into barriers to sharing and related concerns on data misuse are included.

  5. Do reading and spelling share a lexicon?

    Science.gov (United States)

    Jones, Angela C; Rawson, Katherine A

    2016-05-01

    In the reading and spelling literature, an ongoing debate concerns whether reading and spelling share a single orthographic lexicon or rely upon independent lexica. Available evidence tends to support a single lexicon account over an independent lexica account, but evidence is mixed and open to alternative explanation. In the current work, we propose another, largely ignored account--separate-but-shared lexica--according to which reading and spelling have separate orthographic lexica, but information can be shared between them. We report three experiments designed to competitively evaluate these three theoretical accounts. In each experiment, participants learned new words via reading training and/or spelling training. The key manipulation concerned the amount of reading versus spelling practice a given item received. Following training, we assessed both response time and accuracy on final outcome measures of reading and spelling. According to the independent lexica account, final performance in one modality will not be influenced by the level of practice in the other modality. According to the single lexicon account, final performance will depend on the overall amount of practice regardless of modality. According to the separate-but-shared account, final performance will be influenced by the level of practice in both modalities but will benefit more from same-modality practice. Results support the separate-but-shared account, indicating that reading and spelling rely upon separate lexica, but information can be shared between them. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Sociality, selection, and survival: simulated evolution of mortality with intergenerational transfers and food sharing.

    Science.gov (United States)

    Lee, Ronald

    2008-05-20

    Why do humans survive so long past reproductive age, and why does juvenile mortality decline after birth, both contrary to the classic theory of aging? Previous work has shown formally that intergenerational transfers can explain both these patterns. Here, simulations confirm those results under weaker assumptions and explore how different social arrangements shape life-history evolution. Simulated single-sex hunter-gatherers survive, forage, reproduce, and share food with kin and nonkin in ways guided by the ethnographic literature. Natural selection acts on probabilistically occurring deleterious mutations. Neither stable population age distributions nor homogeneous genetic lineages are assumed. When food is shared only within kin groups, an infant death permits reallocation of its unneeded food to the infant's kin, offsetting the fitness cost of the death and weakening the force of selection against infant mortality. Thus, evolved infant mortality is relatively high, more so in larger kin groups. Food sharing with nonkin reduces the costs to kin of child rearing, but also reduces the resources recaptured by kin after an infant death, so evolved infant mortality is lower. Postreproductive adults transfer food to descendants, enhancing their growth and survival, so postreproductive survival is selected. The force of selection for old-age survival depends in complicated ways on the food-sharing arrangements. Population-level food sharing with nonkin leads to the classic pattern of constant low mortality up to sexual maturity and no postreproductive survival.

  7. Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma.

    Science.gov (United States)

    Schwabova, Jaroslava; Brozkova, Dana Safka; Petrak, Borivoj; Mojzisova, Mahulena; Pavlickova, Klara; Haberlova, Jana; Mrazkova, Lenka; Hedvicakova, Petra; Hornofova, Ludmila; Kaluzova, Marie; Fencl, Filip; Krutova, Marcela; Zamecnik, Josef; Seeman, Pavel

    2013-12-01

    Pontocerebellar hypoplasia type 1 (PCH1) is characterized by cerebellar and anterior horn motor neuron degeneration and loss, signs of spinal muscular atrophy plus. Patients manifest severe perinatal weakness, hypotonia, and respiratory insufficiency, causing death frequently before the age of 1 year. Recently, causative mutations in EXOSC3 were reported in a majority of PCH1 patients, but the detailed clinical phenotype caused by EXOSC3 mutations, genotype-phenotype correlations, and prevalent mutations in specific ethnic groups is not yet known. Three unrelated Czech Roma patients with PCH1 were investigated clinically, electrophysiologically, neuroradiologically, and neuropathologically (patients 1 and 2). The entire coding region of the EXOSC3 gene, including the adjacent intron sequences, was sequenced in all three patients. The same mutation c.92G→C, p.G31A in EXOSC3 was found in all three affected patients in homozygous state and in heterozygous state in the parents from two of the families. Haplotype analysis with four flanking microsatellite markers showed identical haplotype in 9 out of 11 haplotypes carrying the c.92G→C, p.G31A mutation. Furthermore, four heterozygotes for this mutation were found in anonymous DNA samples from 90 unrelated Roma individuals. All four of these samples shared the same haplotype. No heterozygous sample was found among 120 anonymous DNA samples from Czech non-Roma individuals with no familial relation. It may therefore be concluded that EXOSC3 c.92G→C, p.G31A mutation is a founder mutation with high prevalence among the Czech Roma causing a similar and particularly severe phenotype of PCH1. These observations from the Czech Roma may have consequences also for other Roma from other countries. PCH1 caused by EXOSC3 founder mutation c.92G→C, p.G31A extends the list of autosomal recessive disorders rare among the general population but more frequent among Roma at least in the Czech Republic.

  8. FAIRNESS OF SHARING PROTECTION FOR MULTICAST IN WDM NETWORKS

    Institute of Scientific and Technical Information of China (English)

    Li Yonggang; Jin Yaohui; Li Lemin

    2008-01-01

    In this paper,the sharing schemes of multicast in survivable Wavelength-Division Multiplexed (WDM) networks are studied and the concept of Shared Risk Link Group (SRLG) is considered.While the network resources are shared by the backup paths,the sharing way is possible to make the backup paths selfish. This selfishness leads the redundant hops of the backup route and a large number of primary lightpaths to share one backup link. The sharing schemes,especially,the self-sharing and cross-sharing,are investigated to avoid the selfishness when computing the backup light-tree. In order to decrease the selfishness of the backup paths,it is important to make the sharing links fair to be used.There is a trade-off between the self-sharing and cross-sharing,which is adjusted through simulation to adapt the sharing degree of each sharing scheme and save the network resources.

  9. Information Sharing in a Multi-Echelon Inventory System

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The influence of different information sharing scenarios in a single supplier-single retailer supply chain is analyzed. The five information sharing scenarios are centralized information sharing, full information sharing, supplier-dominated information sharing, retailer-dominated information sharing, and noninformation sharing. Iterative procedures are developed to obtain the inventory policies and the system costs at equilibrium points. Numerical examples show that the cost of a centralized inventory system is about 20% - 40% lower than that of a decentralized system with non-information sharing. Furthermore, a higher information sharing level does not always lead to a lower system cost in a decentralized supply chain due to inventory competition.

  10. Making SharePoint® Chemically Aware™

    Directory of Open Access Journals (Sweden)

    Tallapragada Kartik

    2012-01-01

    Full Text Available Abstract Background The use of SharePoint® collaboration software for content management has become a critical part of today's drug discovery process. SharePoint 2010 software has laid a foundation which enables researchers to collaborate and search on various contents. The amount of data generated during a transition of a single compound from preclinical discovery to commercialization can easily range in terabytes, thus there is a greater demand of a chemically aware search algorithm that supplements SharePoint which enables researchers to query for information in a more intuitive and effective way. Thus by supplementing SharePoint with Chemically Aware™ features provides a great value to the pharmaceutical and biotech companies and makes drug discovery more efficient. Using several tools we have integrated SharePoint with chemical, compound, and reaction databases, thereby improving the traditional search engine capability and enhancing the user experience. Results This paper describes the implementation of a Chemically Aware™ system to supplement SharePoint. A Chemically Aware SharePoint (CASP allows users to tag documents by drawing a structure and associating it with the related content. It also allows the user to search SharePoint software content and internal/external databases by carrying out substructure, similarity, SMILES, and IUPAC name searches. Building on traditional search, CASP takes SharePoint one step further by providing a intuitive GUI to the researchers to base their search on their knowledge of chemistry than textual search. CASP also provides a way to integrate with other systems, for example a researcher can perform a sub-structure search on pdf documents with embedded molecular entities. Conclusion A Chemically Aware™ system supplementing SharePoint is a step towards making drug discovery process more efficient and also helps researchers to search for information in a more intuitive way. It also helps the

  11. Lowering medical costs through the sharing of savings by physicians and patients: inclusive shared savings.

    Science.gov (United States)

    Schmidt, Harald; Emanuel, Ezekiel J

    2014-12-01

    Current approaches to controlling health care costs have strengths and weaknesses. We propose an alternative, "inclusive shared savings," that aims to lower medical costs through savings that are shared by physicians and patients. Inclusive shared savings may be particularly attractive in situations in which treatments, such as those for gastric cancer, are similar in clinical effectiveness and have modest differences in convenience but substantially differ in cost. Inclusive shared savings incorporates features of typical insurance coverage, shared savings, and value-based insurance design but differs from value-based insurance design, which merely seeks to decrease or eliminate out-of-pocket costs. Inclusive shared savings offers financial incentives to physicians and patients to promote the use of lower-cost, but equally effective, interventions and should be evaluated in a rigorous trial or demonstration project.

  12. Shared services – shared necessity: Austerity, reformed local government and reduced budgets1

    Directory of Open Access Journals (Sweden)

    Lloyd Greg

    2015-12-01

    Full Text Available Shared services are now established as a core delivery model in local and regional governance arrangements. Shared services have emerged as a ‘common sense’ delivery vehicle with attendant efficiency and effectiveness gains. There is, however, a more complex intellectual provenance to a reliance on shared services. In essence, shared services are the logical outcome of the deliberate turn to neo-liberal thinking and the various iterations of the new public managerialism methodology which has progressively established itself in local and regional governance over the past thirty years or so. This paper explores the neo-liberal provenance of shared services and considers the consequential vulnerabilities to austerity, administrative reform and reduced public sector budgets. The central proposition of the paper is that while neo-liberal ideas have created the justification for shared services, this has embedded a set of systemic tensions in the delivery model.

  13. Secure Data Sharing In an Untrusted Cloud

    Directory of Open Access Journals (Sweden)

    Rekha Chandankere

    2015-08-01

    Full Text Available Cloud computing is a huge area which basically provides many services on the basis of pay as you go. One of the fundamental services provided by cloud is data storage. Cloud provides cost efficiency and an efficient solution for sharing resource among cloud users. A secure and efficient data sharing scheme for groups in cloud is not an easy task. On one hand customers are not ready to share their identity but on other hand want to enjoy the cost efficiency provided by the cloud. It needs to provide identity privacy, multiple owner and dynamic data sharing without getting effected by the number of cloud users revoked. In this paper, any member of a group can completely enjoy the data storing and sharing services by the cloud. A secure data sharing scheme for dynamic cloud users is proposed in this paper. For which it uses group signature and dynamic broadcast encryption techniques such that any user in a group can share the information in a secured manner. Additionally the permission option is proposed for the security reasons. This means the file access permissions are generated by the admin and given to the user using Role Based Access Control (RBA algorithm. The file access permissions are read, write and delete. In this, owner can provide files with options and accepts the users using that option. The revocation of cloud user is a function generated by the Admin for security purpose. The encryption computational cost and storage overhead is not dependent on the number of users revoked. We analyze the security by proofs and produce the cloud efficiency report using cloudsim.

  14. Connexin32 mutations and Xq13 physical map

    Energy Technology Data Exchange (ETDEWEB)

    Johanson, R.A.; Bone, L.J. [Univ. of Pennsylvania School of Medicine, Philadelphia (United States); Neystat, M. [Columbia Univ., New York, NY (United States)] [and others

    1994-09-01

    Mutations in the gap junction protein connexin32 (Cx32) are associated with X-linked Charcot-Marie-Tooth disease (CMTX). We and others have identified 24 separate mutations in 27 families. The third transmembrane domain of Cx32 has two mutations that occur in multiple families: three unrelated families have the same missense mutation at codon 139 (Val to Met), and two additional unrelated families have a single base change in codon 142 (Arg to Trp). In order to physically map the region surrounding the Cx32 gene and identify regulatory sequences that could be affected by additional mutations, we are developing a contiguous set of YAC clones for the region (Xq13.1-13.3). The YACs were identified primarily by PCR-based screening of total genomic YAC libraries from CEPH and Genethon. Additional YACs were obtained from collaborating investigators and a local library. A total of 41 overlapping YACs were identified with the STSs DXS106, DXS453, DXS348, IL2RG, GJB1(Cx32), CCG1, DXS559, DXS227, DXS986, DXS1197, and DXS128. Overlap between the YACs was determined by shared STS content and by appearance of identical segments in inter-Alu PCR. The set of overlapping YAC clones helps to define the relationship between CMTX/Cx32 and the nearby gene for severe combined immunodeficiency syndrome (SCIDX/IL2RG), and it is now being used in localization of the gene for dystonia-parkinsonism syndrome (lubag disease, DYT3), which also maps to this region.

  15. Beyond shared savings : a multilevel analysis of the perceived value of HR shared services

    OpenAIRE

    Meijerink, J.G.

    2013-01-01

    Human Resource Shared Service Centers are introduced by organizations with the aim to create value for employees and managers. Although several studies uncovered the value potential of HR shared services (e.g. possibilities for reducing costs, improving HR service quality and increasing the strategic contribution of the HRM function), little research has been done that explains how the value of HR shared services is created. Low levels of perceived value may have undesirable consequences such...

  16. HydroShare: An online, collaborative environment for the sharing of hydrologic data and models (Invited)

    Science.gov (United States)

    Tarboton, D. G.; Idaszak, R.; Horsburgh, J. S.; Ames, D.; Goodall, J. L.; Band, L. E.; Merwade, V.; Couch, A.; Arrigo, J.; Hooper, R. P.; Valentine, D. W.; Maidment, D. R.

    2013-12-01

    HydroShare is an online, collaborative system being developed for sharing hydrologic data and models. The goal of HydroShare is to enable scientists to easily discover and access data and models, retrieve them to their desktop or perform analyses in a distributed computing environment that may include grid, cloud or high performance computing model instances as necessary. Scientists may also publish outcomes (data, results or models) into HydroShare, using the system as a collaboration platform for sharing data, models and analyses. HydroShare is expanding the data sharing capability of the CUAHSI Hydrologic Information System by broadening the classes of data accommodated, creating new capability to share models and model components, and taking advantage of emerging social media functionality to enhance information about and collaboration around hydrologic data and models. One of the fundamental concepts in HydroShare is that of a Resource. All content is represented using a Resource Data Model that separates system and science metadata and has elements common to all resources as well as elements specific to the types of resources HydroShare will support. These will include different data types used in the hydrology community and models and workflows that require metadata on execution functionality. HydroShare will use the integrated Rule-Oriented Data System (iRODS) to manage federated data content and perform rule-based background actions on data and model resources, including parsing to generate metadata catalog information and the execution of models and workflows. This presentation will introduce the HydroShare functionality developed to date, describe key elements of the Resource Data Model and outline the roadmap for future development.

  17. Sharing for people, planet or profit? Analysing motivations for intended sharing economy participation

    OpenAIRE

    Böcker, L.; Meelen, A.A.H.

    2016-01-01

    The sharing economy is a fast-growing and heavily debated phenomenon. This study provides an overview of motivations of people willing to participate in different forms of the sharing economy. A survey was held amongst 1,330 respondents from Amsterdam, the Netherlands. Using stated preference data, we investigate the relative importance of (1) economic, (2) social and (3) environmental motivations to participate in peer-to-peer sharing. Hereby we consider differences between (a) sectors of th...

  18. Common Β- Thalassaemia Mutations in

    Directory of Open Access Journals (Sweden)

    P Azarfam

    2005-01-01

    Full Text Available Introduction: β –Thalassaemia was first explained by Thomas Cooly as Cooly’s anaemia in 1925. The β- thalassaemias are hereditary autosomal disorders with decreased or absent β-globin chain synthesis. The most common genetic defects in β-thalassaemias are caused by point mutations, micro deletions or insertions within the β-globin gene. Material and Methods: In this research , 142 blood samples (64 from childrens hospital of Tabriz , 15 samples from Shahid Gazi hospital of Tabriz , 18 from Urumia and 45 samples from Aliasghar hospital of Ardebil were taken from thalassaemic patients (who were previously diagnosed .Then 117 non-familial samples were selected . The DNA of the lymphocytes of blood samples was extracted by boiling and Proteinase K- SDS procedure, and mutations were detected by ARMS-PCR methods. Results: From the results obtained, eleven most common mutations,most of which were Mediterranean mutations were detected as follows; IVS-I-110(G-A, IVS-I-1(G-A ،IVS-I-5(G-C ,Frameshift Codon 44 (-C,( codon5(-CT,IVS-1-6(T-C, IVS-I-25(-25bp del ,Frameshift 8.9 (+G ,IVS-II-1(G-A ,Codon 39(C-T, Codon 30(G-C the mutations of the samples were defined. The results showed that Frameshift 8.9 (+G, IVS-I-110 (G-A ,IVS-II-I(G-A, IVS-I-5(G-C, IVS-I-1(G-A , Frameshift Codon 44(-C , codon5(-CT , IVS-1-6(T-C , IVS-I-25(-25bp del with a frequency of 29.9%, 25.47%,17.83%, 7.00%, 6.36% , 6.63% , 3.8% , 2.5% , 0.63% represented the most common mutations in North - west Iran. No mutations in Codon 39(C-T and Codon 30(G-C were detected. Cunclusion: The frequency of the same mutations in patients from North - West of Iran seems to be different as compared to other regions like Turkey, Pakistan, Lebanon and Fars province of Iran. The pattern of mutations in this region is more or less the same as in the Mediterranean region, but different from South west Asia and East Asia.

  19. Capulet and Slingshot share overlapping functions during Drosophila eye morphogenesis

    Directory of Open Access Journals (Sweden)

    Lin Chiao-Ming

    2012-04-01

    Full Text Available Abstract Background CAP/Capulet (Capt, Slingshot (Ssh and Cofilin/Twinstar (Tsr are actin-binding proteins that restrict actin polymerization. Previously, it was shown that low resolution analyses of loss-of-function mutations in capt, ssh and tsr all show ectopic F-actin accumulation in various Drosophila tissues. In contrast, RNAi depletion of capt, tsr and ssh in Drosophila S2 cells all affect actin-based lamella formation differently. Whether loss of these three related genes might cause the same effect in the same tissue remains unclear. Methods Loss-of-function mutant clones were generated using the MARCM or EGUF system whereas overexpression clones were generated using the Flip-out system. Immunostaining were then performed in eye imaginal discs with clones. FRAP was performed in cultured eye discs. Results Here, we compared their loss-of-function phenotype at single-cell resolution, using a sheet of epithelial cells in the Drosophila eye imaginal disc as a model system. Surprisingly, we found that capt and ssh, but not tsr, mutant cells within and posterior to the morphogenetic furrow (MF shared similar phenotypes. The capt/ssh mutant cells possessed: (1 hexagonal cell packing with discontinuous adherens junctions; and (2 largely complementary accumulation of excessive phosphorylated myosin light chain (p-MLC and F-actin rings at the apical cortex. We further showed that the capt/ssh mutant phenotypes depended on the inactivation of protein kinase A (PKA and activation of Rho. Conclusions Although Capt, Ssh and Tsr were reported to negatively regulate actin polymerization, we found that Capt and Ssh, but not Tsr, share overlapping functions during eye morphogenesis.

  20. EGFR Expression and KRAS and BRAF Mutational Status in Intestinal-Type Sinonasal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Valérie Costes

    2013-03-01

    Full Text Available Accumulation of molecular alterations, including EGFR overexpression and mutations in KRAS and BRAF, contribute to colorectal carcinogenesis. Since intestinal-type adenocarcinoma (ITAC of the nasal cavity and paranasal sinus has morphologic and phenotypic features that are usually indistinguishable from colorectal cancer (CRC, it is likely that both tumor types share equivalent genetic alterations. Data from a series of 43 patients treated surgically for ITAC in Montpellier, France between November 1998 and December 2012 were collected. Tumors were characterized for mutations in KRAS and BRAF as well as EGFR overexpression. Kaplan-Meier survival curves were constructed using overall survival as the primary end points. Patient survival was analyzed using the hazards ratio. Twenty seven tumors (63% showed EGFR positivity and 30% exhibited a high expression level (+2/+3. KRAS mutations were detected in 43% of cases. BRAF mutations were identified in 3.6% of specimens. Patients with age superior to 60 years, metastatic status, and KRAS mutations had significant overall survival values (p = 0.026, p = 0.001 and p = 0.03, respectively. Our results indicate that KRAS mutations and EGFR expression are frequent in ITAC and that KRAS mutations predict good patient prognosis in ITAC. Finally, EGFR directed molecular treatments could be investigated in a subset of patients affected by ITAC.