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Sample records for hypomorphic mecp2 point

  1. MECP2 Duplication Syndrome

    DEFF Research Database (Denmark)

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients...... and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy...... similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P work shows unique data in patients affected by MDS. For the first...

  2. Regulatory functions and pathological relevance of the MECP2 3′UTR in the central nervous system

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    Heather McGowan

    2015-01-01

    Full Text Available Methyl-CpG-binding protein 2 (MeCP2, encoded by the gene MECP2, is a transcriptional regulator and chromatin-remodeling protein, which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system (CNS. Highly enriched in post-migratory neurons, MeCP2 is needed for neuronal maturation, including dendritic arborization and the development of synapses. Loss-of-function mutations in MECP2 cause Rett syndrome (RTT, a debilitating neurodevelopmental disorder characterized by a phase of normal development, followed by the progressive loss of milestones and cognitive disability. While a great deal has been discovered about the structure, function, and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT, including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders, much about this multifunctional protein remains enigmatic. One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range, the limits of which may depend upon the cell type and developmental time point. As such, MeCP2 is amenable to complex, multifactorial regulation. Here, we summarize the role of the MECP2 3' untranslated region (UTR in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.

  3. Circadian cycle-dependent MeCP2 and brain chromatin changes.

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    Alexia Martínez de Paz

    Full Text Available Methyl CpG binding protein 2 (MeCP2 is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome.

  4. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

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    Carl O Olson

    Full Text Available MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum, whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute

  5. Mild expression differences of MECP2 influencing aggressive social behavior.

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    Tantra, Martesa; Hammer, Christian; Kästner, Anne; Dahm, Liane; Begemann, Martin; Bodda, Chiranjeevi; Hammerschmidt, Kurt; Giegling, Ina; Stepniak, Beata; Castillo Venzor, Aracely; Konte, Bettina; Erbaba, Begun; Hartmann, Annette; Tarami, Asieh; Schulz-Schaeffer, Walter; Rujescu, Dan; Mannan, Ashraf U; Ehrenreich, Hannelore

    2014-05-01

    The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior.

  6. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation.

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    Nagarajan, Raman P; Hogart, Amber R; Gwye, Ynnez; Martin, Michelle R; LaSalle, Janine M

    2006-01-01

    Mutations in MECP2, encoding methyl CpG binding protein 2 (MeCP2), cause most cases of Rett syndrome (RTT), an X-linked neurodevelopmental disorder. Both RTT and autism are "pervasive developmental disorders" and share a loss of social, cognitive and language skills and a gain in repetitive stereotyped behavior, following apparently normal perinatal development. Although MECP2 coding mutations are a rare cause of autism, MeCP2 expression defects were previously found in autism brain. To further study the role of MeCP2 in autism spectrum disorders (ASDs), we determined the frequency of MeCP2 expression defects in brain samples from autism and other ASDs. We also tested the hypotheses that MECP2 promoter mutations or aberrant promoter methylation correlate with reduced expression in cases of idiopathic autism. MeCP2 immunofluorescence in autism and other neurodevelopmental disorders was quantified by laser scanning cytometry and compared with control postmortem cerebral cortex samples on a large tissue microarray. A significant reduction in MeCP2 expression compared to age-matched controls was found in 11/14 autism (79%), 9/9 RTT (100%), 4/4 Angelman syndrome (100%), 3/4 Prader-Willi syndrome (75%), 3/5 Down syndrome (60%), and 2/2 attention deficit hyperactivity disorder (100%) frontal cortex samples. One autism female was heterozygous for a rare MECP2 promoter variant that correlated with reduced MeCP2 expression. A more frequent occurrence was significantly increased MECP2 promoter methylation in autism male frontal cortex compared to controls. Furthermore, percent promoter methylation of MECP2 significantly correlated with reduced MeCP2 protein expression. These results suggest that both genetic and epigenetic defects lead to reduced MeCP2 expression and may be important in the complex etiology of autism.

  7. MeCP2 regulates ethanol sensitivity and intake.

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    Repunte-Canonigo, Vez; Chen, Jihuan; Lefebvre, Celine; Kawamura, Tomoya; Kreifeldt, Max; Basson, Oan; Roberts, Amanda J; Sanna, Pietro Paolo

    2014-09-01

    We have investigated the expression of chromatin-regulating genes in the prefrontal cortex and in the shell subdivision of the nucleus accumbens during protracted withdrawal in mice with increased ethanol drinking after chronic intermittent ethanol (CIE) vapor exposure and in mice with a history of non-dependent drinking. We observed that the methyl-CpG binding protein 2 (MeCP2) was one of the few chromatin-regulating genes to be differentially regulated by a history of dependence. As MeCP2 has the potential of acting as a broad gene regulator, we investigated sensitivity to ethanol and ethanol drinking in MeCP2(308/) (Y) mice, which harbor a truncated MeCP2 allele but have a milder phenotype than MeCP2 null mice. We observed that MeCP2(308/) (Y) mice were more sensitive to ethanol's stimulatory and sedative effects than wild-type (WT) mice, drank less ethanol in a limited access 2 bottle choice paradigm and did not show increased drinking after induction of dependence with exposure to CIE vapors. Alcohol metabolism did not differ in MeCP2(308/) (Y) and WT mice. Additionally, MeCP2(308/) (Y) mice did not differ from WT mice in ethanol preference in a 24-hour paradigm nor in their intake of graded solutions of saccharin or quinine, suggesting that the MeCP2(308/) (Y) mutation did not alter taste function. Lastly, using the Gene Set Enrichment Analysis algorithm, we found a significant overlap in the genes regulated by alcohol and by MeCP2. Together, these results suggest that MeCP2 contributes to the regulation of ethanol sensitivity and drinking. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  8. MECP2 promoter methylation and X chromosome inactivation in autism.

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    Nagarajan, Raman P; Patzel, Katherine A; Martin, Michelle; Yasui, Dag H; Swanberg, Susan E; Hertz-Picciotto, Irva; Hansen, Robin L; Van de Water, Judy; Pessah, Isaac N; Jiang, Ruby; Robinson, Wendy P; LaSalle, Janine M

    2008-06-01

    Epigenetic mechanisms have been proposed to play a role in the etiology of autism. This hypothesis is supported by the discovery of increased MECP2 promoter methylation associated with decreased MeCP2 protein expression in autism male brain. To further understand the influence of female X chromosome inactivation (XCI) and neighboring methylation patterns on aberrant MECP2 promoter methylation in autism, multiple methylation analyses were peformed on brain and blood samples from individuals with autism. Bisulfite sequencing analyses of a region 0.6 kb upstream of MECP2 in brain DNA samples revealed an abrupt transition from a highly methylated region in both sexes to a region unmethylated in males and subject to XCI in females. Chromatin immunoprecipitation analysis demonstrated that the CCTC-binding factor (CTCF) bound to this transition region in neuronal cells, consistent with a chromatin boundary at the methylation transition. Male autism brain DNA samples displayed a slight increase in methylation in this transition region, suggesting a possible aberrant spreading of methylation into the MECP2 promoter in autism males across this boundary element. In addition, autistic female brain DNA samples showed evidence for aberrant MECP2 promoter methylation as an increase in the number of bisulfite sequenced clones with undefined XCI status for MECP2 but not androgen receptor (AR). To further investigate the specificity of MECP2 methylation alterations in autism, blood DNA samples from females and mothers of males with autism were also examined for XCI skewing at AR, but no significant increase in XCI skewing was observed compared to controls. These results suggest that the aberrant MECP2 methylation in autism brain DNA samples is due to locus-specific rather than global X chromosome methylation changes.

  9. Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes.

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    Robby M Zachariah

    Full Text Available Rett Syndrome (RTT is a severe neurological disorder in young females, and is caused by mutations in the X-linked MECP2 gene. MECP2/Mecp2 gene encodes for two protein isoforms; MeCP2E1 and MeCP2E2 that are identical except for the N-terminus region of the protein. In brain, MECP2E1 transcripts are 10X higher, and MeCP2E1 is suggested to be the relevant isoform for RTT. However, due to the unavailability of MeCP2 isoform-specific antibodies, the endogenous expression pattern of MeCP2E1 is unknown. To gain insight into the expression of MeCP2E1 in brain, we have developed an anti-MeCP2E1 antibody and validated its specificity in cells exogenously expressing individual MeCP2 isoforms. This antibody does not show any cross-reactivity with MeCP2E2 and detects endogenous MeCP2E1 in mice brain, with no signal in Mecp2(tm1.1Bird y/- null mice. Additionally, we show the endogenous MeCP2E1 expression throughout different brain regions in adult mice, and demonstrate its highest expression in the brain cortex. Our results also indicate that MeCP2E1 is highly expressed in primary neurons, as compared to primary astrocytes. This is the first report of the endogenous MeCP2E1 expression at the protein levels, providing novel avenues for understanding different aspects of MeCP2 function.

  10. Early progressive encephalopathy in boys and MECP2 mutations.

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    Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K

    2006-07-11

    MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

  11. MeCP2-Related Diseases and Animal Models

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    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  12. Role of Mecp2 in Experience-Dependent Epigenetic Programming

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    Christoph A. Zimmermann

    2015-03-01

    Full Text Available Mutations in the X-linked gene MECP2, the founding member of a family of proteins recognizing and binding to methylated DNA, are the genetic cause of a devastating neurodevelopmental disorder in humans, called Rett syndrome. Available evidence suggests that MECP2 protein has a critical role in activity-dependent neuronal plasticity and transcription during brain development. Moreover, recent studies in mice show that various posttranslational modifications, notably phosphorylation, regulate Mecp2’s functions in learning and memory, drug addiction, depression-like behavior, and the response to antidepressant treatment. The hypothalamic-pituitary-adrenal (HPA axis drives the stress response and its deregulation increases the risk for a variety of mental disorders. Early-life stress (ELS typically results in sustained HPA-axis deregulation and is a major risk factor for stress related diseases, in particular major depression. Interestingly, Mecp2 protein has been shown to contribute to ELS-dependent epigenetic programming of Crh, Avp, and Pomc, all of these genes enhance HPA-axis activity. Hereby ELS regulates Mecp2 phosphorylation, DNA binding, and transcriptional activities in a tissue-specific and temporospatial manner. Overall, these findings suggest MECP2 proteins are so far underestimated and have a more dynamic role in the mediation of the gene-environment dialog and epigenetic programming of the neuroendocrine stress system in health and disease.

  13. MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.

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    Townend, Gillian S; Ehrhart, Friederike; van Kranen, Henk J; Wilkinson, Mark; Jacobsen, Annika; Roos, Marco; Willighagen, Egon L; van Enckevort, David; Evelo, Chris T; Curfs, Leopold M G

    2018-04-27

    Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data. © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.

  14. Molecular analysis of MECP2 gene in Egyptian patients with Rett ...

    African Journals Online (AJOL)

    Molecular analysis of MECP2 gene in Egyptian patients with Rett syndrome. ... Egyptian Journal of Medical Human Genetics ... This study represents one of the limited MECP2 molecular analyses done on Egyptian patients with RTT, in which direct sequencing of MECP2 coding region in 10 female Egyptian patients ...

  15. Rett Syndrome Mutant Neural Cells Lacks MeCP2 Immunoreactive Bands.

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    Carlos Bueno

    Full Text Available Dysfunctions of MeCP2 protein lead to various neurological disorders such as Rett syndrome and Autism. The exact functions of MeCP2 protein is still far from clear. At a molecular level, there exist contradictory data. MeCP2 protein is considered a single immunoreactive band around 75 kDa by western-blot analysis but several reports have revealed the existence of multiple MeCP2 immunoreactive bands above and below the level where MeCP2 is expected. MeCP2 immunoreactive bands have been interpreted in different ways. Some researchers suggest that multiple MeCP2 immunoreactive bands are unidentified proteins that cross-react with the MeCP2 antibody or degradation product of MeCP2, while others suggest that MeCP2 post-transcriptional processing generates multiple molecular forms linked to cell signaling, but so far they have not been properly analyzed in relation to Rett syndrome experimental models. The purpose of this study is to advance understanding of multiple MeCP2 immunoreactive bands in control neural cells and p.T158M MeCP2e1 mutant cells. We have generated stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Application of N- and C- terminal MeCP2 antibodies, and also, RFP antibody minimized concerns about nonspecific cross-reactivity, since they react with the same antigen at different epitopes. We report the existence of multiple MeCP2 immunoreactive bands in control cells, stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Also, MeCP2 immunoreactive bands differences were found between wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Slower migration phosphorylated band around 70kDa disappeared in p.T158M MeCP2e1-RFP mutant expressing cells. These data suggest that threonine 158 could represent an important phosphorylation site potentially involved in protein function. Our results clearly indicate that MeCP2 antibodies have no cross-reactivity with similar epitopes on others proteins, supporting the idea that MeCP2 may exist in multiple different molecular forms and that molecular pattern variations derived from altered post-transcriptional processing may underlay Rett syndrome physiophatology.

  16. Evolving role of MeCP2 in Rett syndrome and autism.

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    LaSalle, Janine M; Yasui, Dag H

    2009-10-01

    Rett syndrome is an X-linked autism-spectrum disorder caused by mutations in MECP2, encoding methyl CpG-binding protein 2. Since the discovery of MECP2 mutations as the genetic cause of Rett syndrome, the understanding of MeCP2 function has evolved. Although MeCP2 was predicted to be a global transcriptional repressor of methylated promoters, large-scale combined epigenomic approaches of MeCP2 binding, methylation and gene expression have demonstrated that MeCP2 binds preferentially to intergenic and intronic regions, and sparsely methylated promoters of active genes. This review compares the evolution of thought within two ‘classic’ epigenetic mechanisms of parental imprinting and X chromosome inactivation to that of the MeCP2 field, and considers the future relevance of integrated epigenomic databases to understanding autism and Rett syndrome.

  17. Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery

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    Sarah E. Sinnett

    2017-06-01

    Full Text Available Intravenous administration of adeno-associated virus serotype 9 (AAV9/hMECP2 has been shown to extend the lifespan of Mecp2−/y mice, but this delivery route induces liver toxicity in wild-type (WT mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM. AAV9/hMECP2 (1 × 1012 viral genomes [vg]; ICM extended Mecp2−/y survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 1012 vg of AAV9/hMECP2 induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of Mecp2−/y mice. Thus, ICM delivery of this vector is impractical as a treatment for Rett syndrome (RTT. To improve the safety of MeCP2 gene therapy, the gene expression cassette was modified to include more endogenous regulatory elements believed to modulate MeCP2 expression in vivo. In Mecp2−/y mice, ICM injection of the modified vector extended lifespan and was well tolerated by the liver but did not rescue RTT behavioral phenotypes. In WT mice, these same doses of the modified vector had no adverse effects on survival or neurological phenotypes. In summary, we identified limitations of the original vector and demonstrated that an improved vector design extends Mecp2−/y survival, without apparent toxicity.

  18. Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

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    Tina Khorshid Ahmad

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

  19. Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

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    Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

    2017-06-12

    Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise

  20. Sex difference in mecp2 expression during a critical period of rat brain development.

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    Kurian, Joseph R; Forbes-Lorman, Robin M; Auger, Anthony P

    2007-09-01

    Pervasive developmental disorder is a classification covering five related conditions including the neurodevelopmental disorder Rett syndrome (RTT) and autism. Of these five conditions, only RTT has a known genetic cause with mutations in Methyl-CpG-binding protein 2 (MeCP2), a global repressor of gene expression, responsible for the majority of RTT cases. However, recent evidence indicates that reduced MeCP2 expression or activity is also found in autism and other disorders with overlapping phenotypes. Considering the sex difference in autism diagnosis, with males diagnosed four times more often than females, we questioned if a sex difference existed in the expression of MeCP2, in particular within the amygdala, a region that develops atypically in autism. We found that male rats express significantly less mecp2 mRNA and protein than females within the amygdala, as well as the ventromedial hypothalamus (VMH), but not within the preoptic area (POA) on post-natal day 1 (PN1). At PN10 these differences were gone; however, on this day males had more mecp2 mRNA than females within the POA. The transient sex difference of mecp2 expression during the steroid-sensitive period of brain development suggests that mecp2 may participate in normal sexual differentiation of the rat brain. Considering the strong link between MeCP2 and neurodevelopmental disorders, the lower levels of mecp2 expression in males may also underlie a biological risk for mecp2-related neural disorders.

  1. Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures.

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    Bodda, Chiranjeevi; Tantra, Martesa; Mollajew, Rustam; Arunachalam, Jayamuruga P; Laccone, Franco A; Can, Karolina; Rosenberger, Albert; Mironov, Sergej L; Ehrenreich, Hannelore; Mannan, Ashraf U

    2013-07-01

    An intriguing finding about the gene encoding methyl-CpG binding protein 2 (MeCP2) is that the loss-of-function mutations cause Rett syndrome and duplication (gain-of-function) of MECP2 leads to another neurological disorder termed MECP2 duplication syndrome. To ensure proper neurodevelopment, a precise regulation of MeCP2 expression is critical, and any gain or loss of MeCP2 over a narrow threshold level may lead to postnatal neurological impairment. To evaluate MeCP2 dosage effects, we generated Mecp2(WT_EGFP) transgenic (TG) mouse in which MeCP2 (endogenous plus TG) is mildly overexpressed (approximately 1.5×). The TG MeCP2(WT_EGFP) fusion protein is functionally active, as cross breeding of these mice with Mecp2 knockout mice led to alleviation of major phenotypes in the null mutant mice, including premature lethality. To characterize the Mecp2(WT_EGFP) mouse model, we performed an extensive battery of behavioral tests, which revealed that these mice manifest increased aggressiveness and higher pentylenetetrazole (PTZ)-induced seizure propensity. Evaluation of neuronal parameters revealed a reduction in the number of tertiary branching sites and increased spine density in Mecp2(WT_EGFP) transgenic (TG) neurons. Treatment of TG neurons with epileptogenic compound-PTZ led to a marked increase in amplitude and frequency of calcium spikes. Based on our ex vivo and in vivo data, we conclude that epileptic seizures are manifested as the first symptom when MeCP2 is mildly overexpressed in mice. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. MeCP2 Rett mutations affect large scale chromatin organization

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    Gupta, Noopur Agarwal; Becker, Annette; Jost, K Laurence

    2011-01-01

    Rett syndrome is a neurological, X chromosomal-linked disorder associated with mutations in the MECP2 gene. MeCP2 protein has been proposed to play a role in transcriptional regulation as well as in chromatin architecture. Since MeCP2 mutant cells exhibit surprisingly mild changes in gene...... expression, we have now explored the possibility that Rett mutations may affect the ability of MeCP2 to bind and organize chromatin. We found that all but one of the 21 missense MeCP2 mutants analyzed accumulated at heterochromatin and about half of them were significantly affected. Furthermore, two......-thirds of all mutants showed a significantly decreased ability to cluster heterochromatin. Three mutants containing different proline substitutions (P101H, P101R and P152R) were severely affected only in heterochromatin clustering and located far away from the DNA interface in the MeCP2 methyl-binding domain...

  3. Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias

    Science.gov (United States)

    Hara, Munetsugu; Takahashi, Tomoyuki; Mitsumasu, Chiaki; Igata, Sachiyo; Takano, Makoto; Minami, Tomoko; Yasukawa, Hideo; Okayama, Satoko; Nakamura, Keiichiro; Okabe, Yasunori; Tanaka, Eiichiro; Takemura, Genzou; Kosai, Ken-ichiro; Yamashita, Yushiro; Matsuishi, Toyojiro

    2015-01-01

    Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure. PMID:26073556

  4. CDKL5 is a brain MeCP2 target gene regulated by DNA methylation.

    Science.gov (United States)

    Carouge, Delphine; Host, Lionel; Aunis, Dominique; Zwiller, Jean; Anglard, Patrick

    2010-06-01

    Rett syndrome and its "early-onset seizure" variant are severe neurodevelopmental disorders associated with mutations within the MECP2 and the CDKL5 genes. Antidepressants and drugs of abuse induce the expression of the epigenetic factor MeCP2, thereby influencing chromatin remodeling. We show that increased MeCP2 levels resulted in the repression of Cdkl5 in rat brain structures in response to cocaine, as well as in cells exposed to serotonin, or overexpressing MeCP2. In contrast, Cdkl5 was induced by siRNA-mediated knockdown of Mecp2 and by DNA-methyltransferase inhibitors, demonstrating its regulation by MeCP2 and by DNA methylation. Cdkl5 gene methylation and its methylation-dependent binding to MeCP2 were increased in the striatum of cocaine-treated rats. Our data demonstrate that Cdkl5 is a MeCP2-repressed target gene providing a link between genes the mutation of which generates overlapping symptoms. They highlight DNA methylation changes as a potential mechanism participating in the long-term plasticity triggered by pharmacological agents.

  5. De novo MECP2 frameshift mutation in a boy with moderate mental retardation, obesity and gynaecomastia.

    NARCIS (Netherlands)

    Kleefstra, T.; Yntema, H.G.; Oudakker, A.R.; Romein, T.; Sistermans, E.A.; Nillessen, W.; Bokhoven, J.H.L.M. van; Vries, L.B.A. de; Hamel, B.C.J.

    2002-01-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene, with apparent lethality in male embryos. However, recent studies indicate that mutations in the MECP2 gene can cause congenital encephalopathy, an Angelman-like phenotype and even nonspecific mental

  6. Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

    Science.gov (United States)

    Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

    2014-01-01

    Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563

  7. MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

    Directory of Open Access Journals (Sweden)

    Valentina Conti

    Full Text Available Rett syndrome (RTT is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

  8. MECP2 duplication phenotype in symptomatic females: report of three further cases

    OpenAIRE

    Novara, Francesca; Simonati, Alessandro; Sicca, Federico; Battini, Roberta; Fiori, Simona; Contaldo, Annarita; Criscuolo, Lucia; Zuffardi, Orsetta; Ciccone, Roberto

    2014-01-01

    Background Xq28 duplications, including MECP2 (methyl CpG-binding protein 2; OMIM 300005), have been identified in approximately 140 male patients presenting with hypotonia, severe developmental delay/intellectual disability, limited or absent speech and ambulation, and recurrent respiratory infections. Female patients with Xq28 duplication have been rarely reported and are usually asymptomatic. Altogether, only fifteen symptomatic females with Xq28 duplications including MECP2 have been repo...

  9. Prenatal diagnosis of foetuses with congenital abnormalities and duplication of the MECP2 region.

    Science.gov (United States)

    Fu, Fang; Liu, Huan-ling; Li, Ru; Han, Jin; Yang, Xin; Min, Pan; Zhen, Li; Zhang, Yong-ling; Xie, Gui-e; Lei, Ting-ying; Li, Yan; Li, Jian; Li, Dong-zhi; Liao, Can

    2014-08-10

    MECP2 duplication results in a well-recognised syndrome in 100% of affected male children; this syndrome is characterised by severe neurodevelopmental disabilities and recurrent infections. However, no sonographic findings have been reported for affected foetuses, and prenatal molecular diagnosis has not been possible for this disease due to lack of prenatal clinical presentation. In this study, we identified a small duplication comprising the MECP2 and L1CAM genes in the Xq28 region in a patient from a family with severe X-linked mental retardation and in a prenatal foetus with brain structural abnormalities. Using high-resolution chromosome microarray analysis (CMA) to screen 108 foetuses with congenital structural abnormalities, we identified additional three foetuses with the MECP2 duplication. Our study indicates that ventriculomegaly, hydrocephalus, agenesis of the corpus callosum, choroid plexus cysts, foetal growth restriction and hydronephrosis might be common ultrasound findings in prenatal foetuses with the MECP2 duplication and provides the first set of prenatal cases with MECP2 duplication, the ultrasonographic phenotype described in these patients will help to recognise the foetuses with possible MECP2 duplication and prompt the appropriate molecular testing. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Apoptotic Activity of MeCP2 Is Enhanced by C-Terminal Truncating Mutations.

    Directory of Open Access Journals (Sweden)

    Alison A Williams

    Full Text Available Methyl-CpG binding protein 2 (MeCP2 is a widely abundant, multifunctional protein most highly expressed in post-mitotic neurons. Mutations causing Rett syndrome and related neurodevelopmental disorders have been identified along the entire MECP2 locus, but symptoms vary depending on mutation type and location. C-terminal mutations are prevalent, but little is known about the function of the MeCP2 C-terminus. We employ the genetic efficiency of Drosophila to provide evidence that expression of p.Arg294* (more commonly identified as R294X, a human MECP2 E2 mutant allele causing truncation of the C-terminal domains, promotes apoptosis of identified neurons in vivo. We confirm this novel finding in HEK293T cells and then use Drosophila to map the region critical for neuronal apoptosis to a small sequence at the end of the C-terminal domain. In vitro studies in mammalian systems previously indicated a role of the MeCP2 E2 isoform in apoptosis, which is facilitated by phosphorylation at serine 80 (S80 and decreased by interactions with the forkhead protein FoxG1. We confirm the roles of S80 phosphorylation and forkhead domain transcription factors in affecting MeCP2-induced apoptosis in Drosophila in vivo, thus indicating mechanistic conservation between flies and mammalian cells. Our findings are consistent with a model in which C- and N-terminal interactions are required for healthy function of MeCP2.

  11. A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation.

    Science.gov (United States)

    Tokaji, Narumi; Ito, Hiromichi; Kohmoto, Tomohiro; Naruto, Takuya; Takahashi, Rizu; Goji, Aya; Mori, Tatsuo; Toda, Yoshihiro; Saito, Masako; Tange, Shoichiro; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

    2018-03-01

    Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting females. It is mainly caused by loss-of-function mutations that affect the coding sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal encephalopathy resulting in death before the age of 2 years is the most common phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in females, and only one case of a male patient with MECP2-related severe neonatal encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is the first reported case of a male with classic RTT caused by a 5-bp duplication in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform, which has been reported in one female patient with classic RTT. Therefore, both males and females displaying at least some type of MeCP2_e1 mutation may exhibit the classic RTT phenotype. © 2018 Wiley Periodicals, Inc.

  12. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2

    Directory of Open Access Journals (Sweden)

    Yunjia Zhang

    2016-06-01

    Full Text Available ABSTRACT MicroRNAs (miRNAs are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

  13. MeCP2 interacts with HP1 and modulates its heterochromatin association during myogenic differentiation

    Science.gov (United States)

    Agarwal, Noopur; Hardt, Tanja; Brero, Alessandro; Nowak, Danny; Rothbauer, Ulrich; Becker, Annette; Leonhardt, Heinrich; Cardoso, M. Cristina

    2007-01-01

    There is increasing evidence of crosstalk between epigenetic modifications such as histone and DNA methylation, recognized by HP1 and methyl CpG-binding proteins, respectively. We have previously shown that the level of methyl CpG-binding proteins increased dramatically during myogenesis leading to large-scale heterochromatin reorganization. In this work, we show that the level of HP1 isoforms did not change significantly throughout myogenic differentiation but their localization did. In particular, HP1γ relocalization to heterochromatin correlated with MeCP2 presence. Using co-immunoprecipitation assays, we found that these heterochromatic factors interact in vivo via the chromo shadow domain of HP1 and the first 55 amino acids of MeCP2. We propose that this dynamic interaction of HP1 and MeCP2 increases their concentration at heterochromatin linking two major gene silencing pathways to stabilize transcriptional repression during differentiation. PMID:17698499

  14. Sequential chromatin immunoprecipitation to detect SUMOylated MeCP2 in neurons

    Directory of Open Access Journals (Sweden)

    Tao Wu

    2016-03-01

    Full Text Available The small ubiquitin-like modifier (SUMO is a short peptide that can be covalently linked to proteins altering their function. SUMOylation is an essential post-translational modification (PTM. Because of its dynamic nature, low abundance levels, and technical limitations, the occupation of endogenous SUMOylated transcription factors at genomic loci is challenging to detect. The chromatin regulator Methyl CpG binding protein 2 (MeCP2 is subjected to PTMs including SUMO. Mutations in MeCP2 lead to Rett syndrome, a severe neurodevelopmental disorder. Here, we present an efficient method to perform sequential chromatin immunoprecipitation (Seq-ChIP for detecting SUMOylated MeCP2 in neurons. This Seq-ChIP technique is a useful tool to determine the occupancy of SUMOylated transcription and chromatin factors at specific genomic regions.

  15. Disease modeling using embryonic stem cells: MeCP2 regulates nuclear size and RNA synthesis in neurons

    NARCIS (Netherlands)

    S. Yazdani (Saami); R. Deogracias (Rubén); J.A. Guy (Jacqueline); R.A. Poot (Raymond); A. Bird (Adrian); Y.A. Barde

    2012-01-01

    textabstractMutations in the gene encoding the methyl-CpG-binding protein MECP2 are the major cause of Rett syndrome, an autism spectrum disorder mainly affecting young females. MeCP2 is an abundant chromatin-associated protein, but how and when its absence begins to alter brain function is still

  16. Functional assessment of MeCP2 in Rett syndrome and cancers of breast, colon, and prostate.

    Science.gov (United States)

    Pandey, Somnath; Pruitt, Kevin

    2017-06-01

    Ever since the first report that mutations in methyl-CpG-binding protein 2 (MeCP2) causes Rett syndrome (RTT), a severe neurological disorder in females world-wide, there has been a keen interest to gain a comprehensive understanding of this protein. While the classical model associated with MeCP2 function suggests its role in gene suppression via recruitment of co-repressor complexes and histone deacetylases to methylated CpG-sites, recent discoveries have brought to light its role in transcription activation, modulation of RNA splicing, and chromatin compaction. Various post-translational modifications (PTMs) of MeCP2 further increase its functional versatility. Involvement of MeCP2 in pathologies other than RTT, such as tumorigenesis however, remains poorly explored and understood. This review provides a survey of the literature implicating MeCP2 in breast, colon and prostate cancer.

  17. Increasing brain serotonin corrects CO2 chemosensitivity in methyl-CpG-binding protein 2 (Mecp2)-deficient mice

    Science.gov (United States)

    Toward, Marie A.; Abdala, Ana P.; Knopp, Sharon J.; Paton, Julian F. R.; Bissonnette, John M.

    2013-01-01

    Mice deficient in the transcription factor methyl-CpG-binding protein 2 (Mecp2), a mouse model of Rett syndrome, display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. In addition, patients with Rett syndrome and male mice that are null for Mecp2 show reduced levels of brain serotonin (5-HT). Serotonin is known to play a role in central chemosensitivity, and we hypothesized that increasing the availability of 5-HT in this mouse model would improve their respiratory response to CO2. Here we determined the apnoeic threshold in heterozygous Mecp2-deficient female mice and examined the effects of blocking 5-HT reuptake on the CO2 response in Mecp2-null male mice. Studies were performed in B6.129P2(C)-Mecp2τm1.1Bird null males and heterozygous females. In an in situ preparation, seven of eight Mecp2-deficient heterozygous females showed arrest of phrenic nerve activity when arterial CO2 was lowered to 3%, whereas the wild-types maintained phrenic nerve amplitude at 53 ± 3% of maximal. In vivo plethysmography studies were used to determine CO2 chemosensitivity in null males. These mice were exposed sequentially to 1, 3 and 5% CO2. The percentage increase in minute ventilation in response to increased inspired CO2 was less in Mecp2−/y than in Mecp2+/y mice. Pretreatment with citalopram, a selective 5-HT reuptake inhibitor (2.5 mg kg−1 I.P.), 40 min prior to CO2 exposure, in Mecp2−/y mice resulted in an improvement in CO2 chemosensitivity to wild-type levels. These results suggest that decreased 5-HT in Mecp2-deficient mice reduces CO2 chemosensitivity, and restoring 5-HT levels can reverse this effect. PMID:23180809

  18. Progressive Encephalopathy in Boys with Symptoms of Rett Syndrome and MECP2 Mutations

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-08-01

    Full Text Available Four young boys with neonatal onset of encephalopathy, a progressive course, and MECP2 mutations are reported from the University of Alabama, Birmingham, AL Symptoms suggestive of Rett syndrome included failure to thrive, respiratory insufficiency, microcephaly, hypotonia, movement disorder, with myoclonic, dyskinetic, and choreiform patterns, and repetitive face scratching or nose rubbing stereotypies.

  19. Generation and characterization of rat and mouse monoclonal antibodies specific for MeCP2 and their use in X-inactivation studies.

    Directory of Open Access Journals (Sweden)

    K Laurence Jost

    Full Text Available Methyl CpG binding protein 2 (MeCP2 binds DNA, and has a preference for methylated CpGs and, hence, in cells, it accumulates in heterochromatin. Even though it is expressed ubiquitously MeCP2 is particularly important during neuronal maturation. This is underscored by the fact that in Rett syndrome, a neurological disease, 80% of patients carry a mutation in the MECP2 gene. Since the MECP2 gene lies on the X chromosome and is subjected to X chromosome inactivation, affected patients are usually chimeric for wild type and mutant MeCP2. Here, we present the generation and characterization of the first rat monoclonal MeCP2 specific antibodies as well as mouse monoclonal antibodies and a rabbit polyclonal antibody. We demonstrate that our antibodies are suitable for immunoblotting, (chromatin immunoprecipitation and immunofluorescence of endogenous and ectopically expressed MeCP2. Epitope mapping revealed that most of the MeCP2 monoclonal antibodies recognize the C-terminal domain and one the N-terminal domain of MeCP2. Using slot blot analysis, we determined a high sensitivity of all antibodies, detecting amounts as low as 1 ng of MeCP2 protein. Moreover, the antibodies recognize MeCP2 from different species, including human, mouse, rat and pig. Lastly, we have validated their use by analyzing and quantifying X chromosome inactivation skewing using brain tissue of MeCP2 heterozygous null female mice. The new MeCP2 specific monoclonal antibodies described here perform well in a large variety of immunological applications making them a very valuable set of tools for studies of MeCP2 pathophysiology in situ and in vitro.

  20. Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiaoqin; Zhao, Bin; Cheng, Yahui; Yang, Yang; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Zhang, Lei; Lv, Xiongwen; Li, Jun, E-mail: xqwu01@foxmail.com

    2015-10-01

    Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G{sub 0}/G{sub 1} cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells. - Highlights: • MeCP2 plays a key role in the proliferation of human HCC cells. • Melittin reduces MeCP2 expression in vitro. • Melittin induces G{sub 0}/G{sub 1} cell cycle arrest in SMMC-7721 cells. • MeCP2 modulates the Shh signaling pathway in SMMC-7721 cells. • Melittin blocks the Shh signaling pathway in SMMC-7721 cells.

  1. Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells

    International Nuclear Information System (INIS)

    Wu, Xiaoqin; Zhao, Bin; Cheng, Yahui; Yang, Yang; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Zhang, Lei; Lv, Xiongwen; Li, Jun

    2015-01-01

    Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G 0 /G 1 cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells. - Highlights: • MeCP2 plays a key role in the proliferation of human HCC cells. • Melittin reduces MeCP2 expression in vitro. • Melittin induces G 0 /G 1 cell cycle arrest in SMMC-7721 cells. • MeCP2 modulates the Shh signaling pathway in SMMC-7721 cells. • Melittin blocks the Shh signaling pathway in SMMC-7721 cells.

  2. Updating the profile of C-terminal MECP2 deletions in Rett syndrome

    Science.gov (United States)

    Bebbington, A; Percy, A; Christodoulou, J; Ravine, D; Ho, G; Jacoby, P; Anderson, A; Pineda, M; Ben Zeev, B; Bahi-Buisson, N; Smeets, E; Leonard, H

    2014-01-01

    Objectives This study aimed to compare the phenotype of Rett syndrome cases with C-terminal deletions to that of cases with different MECP2 mutations and to examine the phenotypic variation within C-terminal deletions. Methods Cases were selected from InterRett, an international database and from the population-based Australian Rett Syndrome Database. Cases (n=832) were included if they had a pathogenic MECP2 mutation in which the nature of the amino acid change was known. Three severity scale systems were used, and individual aspects of the phenotype were also compared. Results Lower severity was associated with C-terminal deletions (n=79) compared to all other MECP2 mutations (e.g. Pineda scale C-terminals mean 15.0 (95% CI 14.0–16.0) vs 16.2 (15.9–16.5). Cases with C-terminal deletions were more likely to have a normal head circumference (odds ratio 3.22, 95% CI 1.53 – 6.79) and weight (odds ratio 2.97, 95% CI 1.25–5.76). Onset of stereotypies tended to be later (median age 2.5 years vs 2 years, pmiddle of the range. In terms of individual aspects of phenotype growth and ability to ambulate appear to be particular strengths. By pooling data internationally this study has achieved the case numbers to provide a phenotypic profile of C-terminal deletions in Rett syndrome. PMID:19914908

  3. Histone Variants and Composition in the Developing Brain: Should MeCP2 Care?

    Science.gov (United States)

    Zago, Valentina; Pinar-CabezaDeVaca, Cristina; Vincent, John B; Ausio, Juan

    2017-01-01

    Specific compositional chromatin features distinguish brain/neuronal chromatin from that of other tissues and are critical to this organ and cell type development and neuroplasticity. These features include a significant turnover of the major constitutive chromosomal proteins, including the (canonical) replication-dependent histones, the replication-independent replacement histone variants, as well as the chromatin associated transcriptional regulator MeCP2 (methyl CpG binding protein 2). Alterations of histones and MeCP2 have already been implicated in many brain disorders. Despite the relevance of histone variants to chromatin structure and function, only recently has some exciting literature started to re-emerge that directly relates them to neuron plasticity and cognition. However, the amount of information available on the functional role of these histones is still very limited. The purpose of this review is to focus attention to this important group of chromatin proteins, which, in the brain, possess overlapping structural and functional roles with the highly abundant presence of MeCP2. There is an imperative need to understand how all these proteins communicate with each other, and future research will hopefully provide us with answers.

  4. A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene

    Energy Technology Data Exchange (ETDEWEB)

    Fendri-Kriaa, Nourhene, E-mail: nourhene.fendri@gmail.com [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Hsairi, Ines [Service de Neurologie Infantile, C.H.U. Hedi Chaker de Sfax (Tunisia); Kifagi, Chamseddine [Laboratoire internationale associe LIA135, Centre de Biotechnologie de Sfax (Tunisia); Ellouze, Emna [Service de Neurologie Infantile, C.H.U. Hedi Chaker de Sfax (Tunisia); Mkaouar-Rebai, Emna [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Triki, Chahnez [Service de Neurologie Infantile, C.H.U. Hedi Chaker de Sfax (Tunisia); Fakhfakh, Faiza [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)

    2011-06-03

    Highlights: {yields} Sequencing of the MECP2 gene, modeling and comparison of the two variants were performed in a Tunisian classical Rett patient. {yields} A double-mutation: a new and de novo mutation c.535C > T and the common one c.763C > T of the MECP2 gene was identified. {yields} The P179S transition may change local electrostatic properties which may affect the function and stability of the protein MeCP2. -- Abstract: Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C > T (p.P179S) and the common c.763C > T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein.

  5. A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene

    International Nuclear Information System (INIS)

    Fendri-Kriaa, Nourhene; Hsairi, Ines; Kifagi, Chamseddine; Ellouze, Emna; Mkaouar-Rebai, Emna; Triki, Chahnez; Fakhfakh, Faiza

    2011-01-01

    Highlights: → Sequencing of the MECP2 gene, modeling and comparison of the two variants were performed in a Tunisian classical Rett patient. → A double-mutation: a new and de novo mutation c.535C > T and the common one c.763C > T of the MECP2 gene was identified. → The P179S transition may change local electrostatic properties which may affect the function and stability of the protein MeCP2. -- Abstract: Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C > T (p.P179S) and the common c.763C > T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein.

  6. Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons

    Science.gov (United States)

    Sampathkumar, Charanya; Wu, Yuan-Ju; Vadhvani, Mayur; Trimbuch, Thorsten; Eickholt, Britta; Rosenmund, Christian

    2016-01-01

    Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system. DOI: http://dx.doi.org/10.7554/eLife.19374.001 PMID:27782879

  7. Differential Expression and Regulation of Brain-Derived Neurotrophic Factor (BDNF) mRNA Isoforms in Brain Cells from Mecp2(308/y) Mouse Model.

    Science.gov (United States)

    Rousseaud, Audrey; Delépine, Chloé; Nectoux, Juliette; Billuart, Pierre; Bienvenu, Thierry

    2015-08-01

    Rett syndrome (RTT) is a severe neurodevelopmental disease caused by mutations in methyl-CpG-binding protein 2 (MECP2), which encodes a transcriptional modulator of many genes including BDNF. BDNF comprises nine distinct promoter regions, each triggering the expression of a specific transcript. The role of this diversity of transcripts remains unknown. MeCP2 being highly expressed in neurons, RTT was initially considered as a neuronal disease. However, recent studies have shown that MeCP2 was also expressed in astrocytes. Though several studies explored Bdnf IV expression in Mecp2-deficient mice, the differential expression of Bdnf isoforms in Mecp2-deficient neurons and astrocytes was never studied. By using TaqMan technology and a mouse model expressing a truncated Mecp2 (Mecp2(308/y)), we firstly showed in neurons that Bdnf transcripts containing exon I, IIb, IIc, IV, and VI are prominently expressed, whereas in astrocytes, Bdnf transcript containing exon VI is preferentially expressed, suggesting a specific regulation of Bdnf expression at the cellular level. Secondly, we confirmed the repressive role of Mecp2 only on the expression of Bdnf VI in neurons. Our data suggested that the truncated Mecp2 protein maintains its function on Bdnf expression regulation in neurons and in astrocytes. Interestingly, we observed that Bdnf transcripts (I and IXA), regulated by neural activity induced by bicuculline in Mecp2(308/y) neurons, were not affected by histone deacetylase inhibition. In contrast, Bdnf transcripts (IIb, IIc, and VI), regulated by histone deacetylation, were not affected by bicuculline treatment in wild-type and Mecp2(308/y) neurons. All these results reflect the complexity of regulation of Bdnf gene.

  8. MeCP2 Promotes Gastric Cancer Progression Through Regulating FOXF1/Wnt5a/β-Catenin and MYOD1/Caspase-3 Signaling Pathways

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    Lingyu Zhao

    2017-02-01

    Full Text Available Methyl-CpG binding protein 2 (MeCP2 has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role in gastric cancer (GC and the molecular mechanism of MeCP2 regulation are still largely unknown. Here we report that MeCP2 is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic features of GC. In our experiments, knockdown of MeCP2 inhibited tumor growth. Molecular mechanism of MeCP2 regulation was investigated using an integrated approach with combination of microarray analysis and chromatin immunoprecipitation sequencing (ChIP-Seq. The results suggest that MeCP2 binds to the methylated CpG islands of FOXF1 and MYOD1 promoters and inhibits their expression at the transcription level. Furthermore, we show that MeCP2 promotes GC cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses apoptosis through MYOD1-mediated Caspase-3 signaling pathway. Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.

  9. MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy

    DEFF Research Database (Denmark)

    Neupane, Manish; Clark, Allison P.; Landini, Serena

    2016-01-01

    An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified methyl cytosine-guanine dinucleotide (CpG) binding protein 2 (MECP2) as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly amplified across 18% of cancers,...

  10. MeCP2 silencing of LncRNA H19 controls hepatic stellate cell proliferation by targeting IGF1R

    International Nuclear Information System (INIS)

    Yang, Jing-Jing; Liu, Li-Ping; Tao, Hui; Hu, Wei; Shi, Peng; Deng, Zi-Yu; Li, Jun

    2016-01-01

    Highlights: • H19 plays a key role in HSCs proliferation and fibrosis. • MeCP2/H19 axis involvement in HSCs activation and fibrosis. • MeCP2 negative controls H19 expression in activated HSCs. • Identification of IGF1R as new target of H19 in HSC. - Abstract: Methyl-CpG-binding protein 2 (MeCP2) plays a key role in liver fibrosis. However, the potential mechanism of MeCP2 in liver fibrosis remains unclear. Early reports suggest that LncRNA H19 is important epigenetic regulator with critical roles in cell proliferation, but its role in hepatic fibrosis remains elusive. Sprague-Dawley rats liver fibrosis was generated by 12-weeks treatment with CCl 4 intraperitoneal injection. HSC-T6 cells were used in vitro study. The expression levels of MeCP2, H19, IGF1R, α-SMA, and Col1A1 were estimated by Western blotting, qRT-PCR and Immunohistochemistry. HSC-T6 cells were transfected with MeCP2-siRNA, pEGF-C1-MeCP2, pEX-3-H19, and H19-siRNA. Finally, cell proliferation ability was assessed by the MTT assay. Here, we found that H19 was significantly down-regulated in HSCs and fibrosis tissues, and an opposite pattern is observed for MeCP2 and IGF1R. Silencing of MeCP2 blocked HSCs proliferation. Knockdown of MeCP2 elevated H19 expression in activated HSCs, and over-expression of MeCP2 inhibited H19 expression in activated HSCs. Moreover, we investigated the effect of H19 on IGF1R expression. Overexpression of H19 in HSCs repressed the expression of IGF1R, and an opposite pattern is observed for H19 silenced. In addition, we reported that overexpression of H19 inhibited the TGF-β1-induced proliferation of HSCs. Furthermore, MeCP2 negative regulation of H19 by targeting the protein IGF1R. Taken together, these results demonstrated that MeCP2 silencing of H19 can alter the IGF1R overexpression, thus contributing to HSCs proliferation. These data could suggest the development of combination therapies that target the MeCP2.

  11. Xq28 duplications including MECP2 in five females: Expanding the phenotype to severe mental retardation.

    Science.gov (United States)

    Bijlsma, E K; Collins, A; Papa, F T; Tejada, M I; Wheeler, P; Peeters, E A J; Gijsbers, A C J; van de Kamp, J M; Kriek, M; Losekoot, M; Broekma, A J; Crolla, J A; Pollazzon, M; Mucciolo, M; Katzaki, E; Disciglio, V; Ferreri, M I; Marozza, A; Mencarelli, M A; Castagnini, C; Dosa, L; Ariani, F; Mari, F; Canitano, R; Hayek, G; Botella, M P; Gener, B; Mínguez, M; Renieri, A; Ruivenkamp, C A L

    2012-06-01

    Duplications leading to functional disomy of chromosome Xq28, including MECP2 as the critical dosage-sensitive gene, are associated with a distinct clinical phenotype in males, characterized by severe mental retardation, infantile hypotonia, progressive neurologic impairment, recurrent infections, bladder dysfunction, and absent speech. Female patients with Xq duplications including MECP2 are rare. Only recently submicroscopic duplications of this region on Xq28 have been recognized in four females, and a triplication in a fifth, all in combination with random X-chromosome inactivation (XCI). Based on this small series, it was concluded that in females with MECP2 duplication and random XCI, the typical symptoms of affected boys are not present. We present clinical and molecular data on a series of five females with an Xq28 duplication including the MECP2 gene, both isolated and as the result of a translocation, and compare them with the previously reported cases of small duplications in females. The collected data indicate that the associated phenotype in females is distinct from males with similar duplications, but the clinical effects may be as severe as seen in males. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  12. Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome.

    Science.gov (United States)

    Samaco, Rodney C; Mandel-Brehm, Caleigh; McGraw, Christopher M; Shaw, Chad A; McGill, Bryan E; Zoghbi, Huda Y

    2012-01-08

    Genomic duplications spanning Xq28 are associated with a spectrum of phenotypes, including anxiety and autism. The minimal region shared among affected individuals includes MECP2 and IRAK1, although it is unclear which gene when overexpressed causes anxiety and social behavior deficits. We report that doubling MECP2 levels causes heightened anxiety and autism-like features in mice and alters the expression of genes that influence anxiety and social behavior, such as Crh and Oprm1. To test the hypothesis that alterations in these two genes contribute to heightened anxiety and social behavior deficits, we analyzed MECP2 duplication mice (MECP2-TG1) that have reduced Crh and Oprm1 expression. In MECP2-TG1 animals, reducing the levels of Crh or its receptor, Crhr1, suppressed anxiety-like behavior; in contrast, reducing Oprm1 expression improved abnormal social behavior. These data indicate that increased MeCP2 levels affect molecular pathways underlying anxiety and social behavior and provide new insight into potential therapies for MECP2-related disorders.

  13. Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus.

    Science.gov (United States)

    Zhang, Ying; Cao, Shu-Xia; Sun, Peng; He, Hai-Yang; Yang, Ci-Hang; Chen, Xiao-Juan; Shen, Chen-Jie; Wang, Xiao-Dong; Chen, Zhong; Berg, Darwin K; Duan, Shumin; Li, Xiao-Ming

    2016-06-01

    Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

  14. Cell cloning-based transcriptome analysis in Rett patients: relevance to the pathogenesis of Rett syndrome of new human MeCP2 target genes.

    Science.gov (United States)

    Nectoux, J; Fichou, Y; Rosas-Vargas, H; Cagnard, N; Bahi-Buisson, N; Nusbaum, P; Letourneur, F; Chelly, J; Bienvenu, T

    2010-07-01

    More than 90% of Rett syndrome (RTT) patients have heterozygous mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene that encodes the methyl-CpG-binding protein 2, a transcriptional modulator. Because MECP2 is subjected to X chromosome inactivation (XCI), girls with RTT either express the wild-type or mutant allele in each individual cell. To test the consequences of MECP2 mutations resulting from a genome-wide transcriptional dysregulation and to identify its target genes in a system that circumvents the functional mosaicism resulting from XCI, we carried out gene expression profiling of clonal populations derived from fibroblast primary cultures expressing exclusively either the wild-type or the mutant MECP2 allele. Clonal cultures were obtained from skin biopsy of three RTT patients carrying either a non-sense or a frameshift MECP2 mutation. For each patient, gene expression profiles of wild-type and mutant clones were compared by oligonucleotide expression microarray analysis. Firstly, clustering analysis classified the RTT patients according to their genetic background and MECP2 mutation. Secondly, expression profiling by microarray analysis and quantitative RT-PCR indicated four up-regulated genes and five down-regulated genes significantly dysregulated in all our statistical analysis, including excellent potential candidate genes for the understanding of the pathophysiology of this neurodevelopmental disease. Thirdly, chromatin immunoprecipitation analysis confirmed MeCP2 binding to respective CpG islands in three out of four up-regulated candidate genes and sequencing of bisulphite-converted DNA indicated that MeCP2 preferentially binds to methylated-DNA sequences. Most importantly, the finding that at least two of these genes (BMCC1 and RNF182) were shown to be involved in cell survival and/or apoptosis may suggest that impaired MeCP2 function could alter the survival of neurons thus compromising brain function without inducing cell death.

  15. Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model [version 1; referees: 2 approved

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    Sampathkumar Rangasamy

    2016-09-01

    Full Text Available Rett syndrome (RTT is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene, encoding methyl-CpG-binding protein 2. We have created a mouse model (Mecp2 A140V “knock-in” mutant expressing the recurrent human MECP2 A140V mutation linked to an X-linked mental retardation/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN cultures from mutant (Mecp2A140V/y and wild type (Mecp2+/y male mice. Cultured hippocampus and cerebellar granule neurons from mutant animals were significantly smaller than neurons from wild type animals. We also examined soma size in hippocampus neurons from individual female transgenic mice that express both a mutant  (maternal allele and a wild type Mecp2 gene linked to an eGFP transgene (paternal allele. In cultures from such doubly heterozygous female mice, the size of neurons expressing the mutant (A140V allele also showed a significant reduction compared to neurons expressing wild type MeCP2, supporting a cell-autonomous role for MeCP2 in neuronal development. IGF-1 (insulin growth factor-1 treatment of neuronal cells from Mecp2 mutant mice rescued the soma size phenotype. We also found that Mecp2  mutation leads to down-regulation of the mTOR signaling pathway, known to be involved in neuronal size regulation. Our results suggest that i reduced neuronal size is an important in vitro cellular phenotype of Mecp2 mutation in mice, and ii MeCP2 might play a critical role in the maintenance of neuronal structure by modulation of the mTOR pathway. The definition of a quantifiable cellular phenotype supports using neuronal size as a biomarker in the development of a high-throughput, in vitro assay to screen for compounds that rescue small neuronal phenotype (“phenotypic assay”.

  16. Structural, Dynamical, and Energetical Consequences of Rett Syndrome Mutation R133C in MeCP2

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    Tugba G. Kucukkal

    2015-01-01

    Full Text Available Rett Syndrome (RTT is a progressive neurodevelopmental disease affecting females. RTT is caused by mutations in the MECP2 gene and various amino acid substitutions have been identified clinically in different domains of the multifunctional MeCP2 protein encoded by this gene. The R133C variant in the methylated-CpG-binding domain (MBD of MeCP2 is the second most common disease-causing mutation in the MBD. Comparative molecular dynamics simulations of R133C mutant and wild-type MBD have been performed to understand the impact of the mutation on structure, dynamics, and interactions of the protein and subsequently understand the disease mechanism. Two salt bridges within the protein and two critical hydrogen bonds between the protein and DNA are lost upon the R133C mutation. The mutation was found to weaken the interaction with DNA and also cause loss of helicity within the 141-144 region. The structural, dynamical, and energetical consequences of R133C mutation were investigated in detail at the atomic resolution. Several important implications of this have been shown regarding protein stability and hydration dynamics as well as its interaction with DNA. The results are in agreement with previous experimental studies and further provide atomic level understanding of the molecular origin of RTT associated with R133C variant.

  17. Characterization of the Relationship of CDKL5 with MeCP2 and Dnmt1 in PrimaryRat Cortical Neurons

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    Zhi Yi

    Full Text Available ABSTRACT Cyclin-dependent kinase-like 5 (CDKL5 is a protein kinase that is homologous to mitogen-activated protein kinases (MAPKs and cyclin-dependent kinases (CDKs. Mutations in the CDKL5 gene cause X-linked infantile spasms and phenotypes that overlap with that of Rett syndrome, which is a neurodevelopmental disorder caused primarily by mutations in the methyl CpG binding protein 2 gene (MECP2. Previous studies in transfected cell lines showed that CDKL5 interacts with MeCP2 and DNA (cytosine-5-methyltransferase 1 (Dnmt1. However, little is known about the relationships of CDKL5 with interacting proteins in primary neuronal cultures. In this study, we investigated the expression patterns of CDKL5, MeCP2 and Dnmt1, and their interaction in cultured rat cortical neurons. Using real-time PCR analysis, we found that CDKL5, MeCP2 and Dnmt1 have similar expression patterns at the mRNA level. In contrast, the expression patterns of those proteins at the protein level are different and could be inversely correlated, as shown by western blotting. Using co-immunoprecipitation, we further demonstrated that CDKL5 interacts with MeCP2 and Dnmt1 in primary rat cortical neurons. These data suggest that a functional link exists among CDKL5, MeCP2 and Dnmt1 during neuronal development and may provide further insight into the pathogenesis of Rett syndrome.

  18. miR-199a Links MeCP2 with mTOR Signaling and Its Dysregulation Leads to Rett Syndrome Phenotypes

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    Keita Tsujimura

    2015-09-01

    Full Text Available Rett syndrome (RTT is a neurodevelopmental disorder caused by MECP2 mutations. Although emerging evidence suggests that MeCP2 deficiency is associated with dysregulation of mechanistic target of rapamycin (mTOR, which functions as a hub for various signaling pathways, the mechanism underlying this association and the molecular pathophysiology of RTT remain elusive. We show here that MeCP2 promotes the posttranscriptional processing of particular microRNAs (miRNAs as a component of the microprocessor Drosha complex. Among the MeCP2-regulated miRNAs, we found that miR-199a positively controls mTOR signaling by targeting inhibitors for mTOR signaling. miR-199a and its targets have opposite effects on mTOR activity, ameliorating and inducing RTT neuronal phenotypes, respectively. Furthermore, genetic deletion of miR-199a-2 led to a reduction of mTOR activity in the brain and recapitulated numerous RTT phenotypes in mice. Together, these findings establish miR-199a as a critical downstream target of MeCP2 in RTT pathogenesis by linking MeCP2 with mTOR signaling.

  19. The intervening domain from MeCP2 enhances the DNA affinity of the methyl binding domain and provides an independent DNA interaction site.

    Science.gov (United States)

    Claveria-Gimeno, Rafael; Lanuza, Pilar M; Morales-Chueca, Ignacio; Jorge-Torres, Olga C; Vega, Sonia; Abian, Olga; Esteller, Manel; Velazquez-Campoy, Adrian

    2017-01-31

    Methyl-CpG binding protein 2 (MeCP2) preferentially interacts with methylated DNA and it is involved in epigenetic regulation and chromatin remodelling. Mutations in MeCP2 are linked to Rett syndrome, the leading cause of intellectual retardation in girls and causing mental, motor and growth impairment. Unstructured regions in MeCP2 provide the plasticity for establishing interactions with multiple binding partners. We present a biophysical characterization of the methyl binding domain (MBD) from MeCP2 reporting the contribution of flanking domains to its structural stability and dsDNA interaction. The flanking disordered intervening domain (ID) increased the structural stability of MBD, modified its dsDNA binding profile from an entropically-driven moderate-affinity binding to an overwhelmingly enthalpically-driven high-affinity binding. Additionally, ID provided an additional site for simultaneously and autonomously binding an independent dsDNA molecule, which is a key feature linked to the chromatin remodelling and looping activity of MeCP2, as well as its ability to interact with nucleosomes replacing histone H1. The dsDNA interaction is characterized by an unusually large heat capacity linked to a cluster of water molecules trapped within the binding interface. The dynamics of disordered regions together with extrinsic factors are key determinants of MeCP2 global structural properties and functional capabilities.

  20. Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations.

    Science.gov (United States)

    Hadzsiev, Kinga; Polgar, Noemi; Bene, Judit; Komlosi, Katalin; Karteszi, Judit; Hollody, Katalin; Kosztolanyi, Gyorgy; Renieri, Alessandra; Melegh, Bela

    2011-03-01

    Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6%). Of the 22 mutations, we identified 7 (31.8%) frameshift-causing deletions, 4 (18.2%) nonsense, 10 (45.5%) missense mutations and one insertion (4.5%). The most frequent pathologic changes were: p.Thr158Met (14.2%) and p.Arg133Cys (11.9%) missense, and p.Arg255Stop (9.5%) and p.Arg294Stop (9.5%) nonsense mutations. We also detected the c.925C >T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G >T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G >T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5%) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations.

  1. Network models predict that reduced excitatory fluctuations can give rise to hippocampal network hyper-excitability in MeCP2-null mice.

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    Ernest C Y Ho

    Full Text Available Rett syndrome is a severe pediatric neurological disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2. Although MeCP2 is expressed near ubiquitously, the primary pathophysiology of Rett syndrome stems from impairments of nervous system function. One alteration within different regions of the MeCP2-deficient brain is the presence of hyper-excitable network responses. In the hippocampus, such responses exist despite there being an overall decrease in spontaneous excitatory drive within the network. In this study, we generated and used mathematical, neuronal network models to resolve this apparent paradox. We did this by taking advantage of previous mathematical modelling insights that indicated that decreased excitatory fluctuations, but not mean excitatory drive, more critically explain observed changes in hippocampal network oscillations from MeCP2-null mouse slices. Importantly, reduced excitatory fluctuations could also bring about hyper-excitable responses in our network models. Therefore, these results indicate that diminished excitatory fluctuations may be responsible for the hyper-excitable state of MeCP2-deficient hippocampal circuitry.

  2. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs.

    Science.gov (United States)

    Leoncini, Silvia; De Felice, Claudio; Signorini, Cinzia; Zollo, Gloria; Cortelazzo, Alessio; Durand, Thierry; Galano, Jean-Marie; Guerranti, Roberto; Rossi, Marcello; Ciccoli, Lucia; Hayek, Joussef

    2015-01-01

    An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) (n = 16) and CDKL5-Rett syndrome (CDKL5-RTT) (n = 8), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.

  3. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs

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    Silvia Leoncini

    2015-01-01

    Full Text Available An involvement of the immune system has been suggested in Rett syndrome (RTT, a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2 or, more rarely, cyclin-dependent kinase-like 5 (CDKL5. To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg response, as well as chemokines, were investigated in MECP2- (MECP2-RTT (n=16 and CDKL5-Rett syndrome (CDKL5-RTT (n=8, before and after ω-3 polyunsaturated fatty acids (PUFAs supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4 were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system.

  4. MeCP2 regulates Tet1-catalyzed demethylation, CTCF binding, and learning-dependent alternative splicing of the BDNF gene in Turtle

    Science.gov (United States)

    Zheng, Zhaoqing; Ambigapathy, Ganesh; Keifer, Joyce

    2017-01-01

    MECP2 mutations underlying Rett syndrome cause widespread misregulation of gene expression. Functions for MeCP2 other than transcriptional are not well understood. In an ex vivo brain preparation from the pond turtle Trachemys scripta elegans, an intraexonic splicing event in the brain-derived neurotrophic factor (BDNF) gene generates a truncated mRNA transcript in naïve brain that is suppressed upon classical conditioning. MeCP2 and its partners, splicing factor Y-box binding protein 1 (YB-1) and methylcytosine dioxygenase 1 (Tet1), bind to BDNF chromatin in naïve but dissociate during conditioning; the dissociation correlating with decreased DNA methylation. Surprisingly, conditioning results in new occupancy of BDNF chromatin by DNA insulator protein CCCTC-binding factor (CTCF), which is associated with suppression of splicing in conditioning. Knockdown of MeCP2 shows it is instrumental for splicing and inhibits Tet1 and CTCF binding thereby negatively impacting DNA methylation and conditioning-dependent splicing regulation. Thus, mutations in MECP2 can have secondary effects on DNA methylation and alternative splicing. DOI: http://dx.doi.org/10.7554/eLife.25384.001 PMID:28594324

  5. MeCP2 Expression and Promoter Methylation of Cyclin D1 Gene Are Associated with Cyclin D1 Expression in Developing Rat Epididymal Duct

    International Nuclear Information System (INIS)

    Darwanto, Agus; Kitazawa, Riko; Mori, Kiyoshi; Kondo, Takeshi; Kitazawa, Sohei

    2008-01-01

    Hypermethylation-dependent silencing of the gene is achieved by recruiting methyl-CpG binding proteins (MeCPs). Among the MeCPs, MeCP2 is the most abundantly and ubiquitously expressed in various types of cells. We first screened the distribution and expression pattern of MeCP2 in adult and developing rat tissues and found strong MeCP2 expression, albeit rather ubiquitously among normal tissues, in ganglion cells and intestinal epithelium in the small intestine, in Purkinje cells and neurons in the brain, in spermatogonia and in epithelial cells in the epididymal duct of the testis. We then assessed the expression and the methylation pattern of the promoter region of cyclin D1 by immunohistochemistry and sodium bisulfite mapping, and found that cyclin D1 expression in the epididymal duct decreased rapidly during rat development: strong in newborn rats and very weak or almost negative in 7-day-old rats. Mirroring the decrease of cyclin D1 expression, methylated cytosine at both CpG and non-CpG loci in the cyclin D1 promoter was frequently observed in the epididymal duct of 7-day-old rats but not in that of newborn rats. Interestingly, MeCP2 expression also increased concomitant with the increase of methylation. Cyclin D1 expression in the epididymal duct may be efficiently regulated by the epigenetic mechanism of the cooperative increase of MeCP2 expression and promoter methylation

  6. Biophysical characterization of the basic cluster in the transcription repression domain of human MeCP2 with AT-rich DNA.

    Science.gov (United States)

    Mushtaq, Ameeq Ul; Lee, Yejin; Hwang, Eunha; Bang, Jeong Kyu; Hong, Eunmi; Byun, Youngjoo; Song, Ji-Joon; Jeon, Young Ho

    2018-01-01

    MeCP2 is a chromatin associated protein which is highly expressed in brain and relevant with Rett syndrome (RTT). There are AT-hook motifs in MeCP2 which can bind with AT-rich DNA, suggesting a role in chromatin binding. Here, we report the identification and characterization of another AT-rich DNA binding motif (residues 295 to 313) from the C-terminal transcription repression domain of MeCP2 by nuclear magnetic resonance (NMR) and isothermal calorimetry (ITC). This motif shows a micromolar affinity to AT-rich DNA, and it binds to the minor groove of DNA like AT-hook motifs. Together with the previous studies, our results provide an insight into a critical role of this motif in chromatin structure and function. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections.

    Science.gov (United States)

    Xu, Xiu; Xu, Qiong; Zhang, Ying; Zhang, Xiaodi; Cheng, Tianlin; Wu, Bingbing; Ding, Yanhua; Lu, Ping; Zheng, Jingjing; Zhang, Min; Qiu, Zilong; Yu, Xiang

    2012-08-21

    Autistic spectrum disorders (ASDs) are a family of neurodevelopmental disorders with strong genetic components. Recent studies have shown that copy number variations in dosage sensitive genes can contribute significantly to these disorders. One such gene is the transcription factor MECP2, whose loss of function in females results in Rett syndrome, while its duplication in males results in developmental delay and autism. Here, we identified a Chinese family with two brothers both inheriting a 2.2 Mb MECP2-containing duplication (151,369,305 - 153,589,577) from their mother. In addition, both brothers also had a 213.7 kb duplication on Chromosome 2, inherited from their father. The older brother also carried a 48.4 kb duplication on Chromosome 2 inherited from the mother, and a 8.2 kb deletion at 11q13.5 inherited from the father. Based on the published literature, MECP2 is the most autism-associated gene among the identified CNVs. Consistently, the boys displayed clinical features in common with other patients carrying MECP2 duplications, including intellectual disability, autism, lack of speech, slight hypotonia and unsteadiness of movement. They also had slight dysmorphic features including a depressed nose bridge, large ears and midface hypoplasia. Interestingly, they did not exhibit other clinical features commonly observed in American-European patients with MECP2 duplication, including recurrent respiratory infections and epilepsy. To our knowledge, this is the first identification and characterization of Chinese Han patients with MECP2-containing duplications. Further cases are required to determine if the above described clinical differences are due to individual variations or related to the genetic background of the patients.

  8. GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells.

    Science.gov (United States)

    Livide, Gabriella; Patriarchi, Tommaso; Amenduni, Mariangela; Amabile, Sonia; Yasui, Dag; Calcagno, Eleonora; Lo Rizzo, Caterina; De Falco, Giulia; Ulivieri, Cristina; Ariani, Francesca; Mari, Francesca; Mencarelli, Maria Antonietta; Hell, Johannes Wilhelm; Renieri, Alessandra; Meloni, Ilaria

    2015-02-01

    Rett syndrome is a monogenic disease due to de novo mutations in either MECP2 or CDKL5 genes. In spite of their involvement in the same disease, a functional interaction between the two genes has not been proven. MeCP2 is a transcriptional regulator; CDKL5 encodes for a kinase protein that might be involved in the regulation of gene expression. Therefore, we hypothesized that mutations affecting the two genes may lead to similar phenotypes by dysregulating the expression of common genes. To test this hypothesis we used induced pluripotent stem (iPS) cells derived from fibroblasts of one Rett patient with a MECP2 mutation (p.Arg306Cys) and two patients with mutations in CDKL5 (p.Gln347Ter and p.Thr288Ile). Expression profiling was performed in CDKL5-mutated cells and genes of interest were confirmed by real-time RT-PCR in both CDKL5- and MECP2-mutated cells. The only major change in gene expression common to MECP2- and CDKL5-mutated cells was for GRID1, encoding for glutamate D1 receptor (GluD1), a member of the δ-family of ionotropic glutamate receptors. GluD1 does not form AMPA or NMDA glutamate receptors. It acts like an adhesion molecule by linking the postsynaptic and presynaptic compartments, preferentially inducing the inhibitory presynaptic differentiation of cortical neurons. Our results demonstrate that GRID1 expression is downregulated in both MECP2- and CDKL5-mutated iPS cells and upregulated in neuronal precursors and mature neurons. These data provide novel insights into disease pathophysiology and identify possible new targets for therapeutic treatment of Rett syndrome.

  9. Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.

    Science.gov (United States)

    Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

    2013-10-22

    Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C 'low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5' promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C 'low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias.

  10. A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections

    Directory of Open Access Journals (Sweden)

    Xu Xiu

    2012-08-01

    Full Text Available Abstract Background Autistic spectrum disorders (ASDs are a family of neurodevelopmental disorders with strong genetic components. Recent studies have shown that copy number variations in dosage sensitive genes can contribute significantly to these disorders. One such gene is the transcription factor MECP2, whose loss of function in females results in Rett syndrome, while its duplication in males results in developmental delay and autism. Case presentation Here, we identified a Chinese family with two brothers both inheriting a 2.2 Mb MECP2-containing duplication (151,369,305 – 153,589,577 from their mother. In addition, both brothers also had a 213.7 kb duplication on Chromosome 2, inherited from their father. The older brother also carried a 48.4 kb duplication on Chromosome 2 inherited from the mother, and a 8.2 kb deletion at 11q13.5 inherited from the father. Based on the published literature, MECP2 is the most autism-associated gene among the identified CNVs. Consistently, the boys displayed clinical features in common with other patients carrying MECP2 duplications, including intellectual disability, autism, lack of speech, slight hypotonia and unsteadiness of movement. They also had slight dysmorphic features including a depressed nose bridge, large ears and midface hypoplasia. Interestingly, they did not exhibit other clinical features commonly observed in American-European patients with MECP2 duplication, including recurrent respiratory infections and epilepsy. Conclusions To our knowledge, this is the first identification and characterization of Chinese Han patients with MECP2-containing duplications. Further cases are required to determine if the above described clinical differences are due to individual variations or related to the genetic background of the patients.

  11. Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations.

    Science.gov (United States)

    Das, Dhanjit Kumar; Raha, Sarbani; Sanghavi, Daksha; Maitra, Anurupa; Udani, Vrajesh

    2013-02-15

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, primarily affecting females and characterized by developmental regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. Rett syndrome is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 270 individual nucleotide changes which cause pathogenic mutations have been reported. However, eight most commonly occurring missense and nonsense mutations account for almost 70% of all patients. We screened 90 individuals with Rett syndrome phenotype. A total of 19 different MECP2 mutations and polymorphisms were identified in 27 patients. Of the 19 mutations, we identified 7 (37%) frameshift, 6 (31%) nonsense, 14 (74%) missense mutations and one duplication (5%). The most frequent pathogenic changes were: missense p.T158M (11%), p.R133C (7.4%), and p.R306C (7.4%) and nonsense p.R168X (11%), p.R255X (7.4%) mutations. We have identified two novel mutations namely p.385-388delPLPP present in atypical patients and p.Glu290AlafsX38 present in a classical patient of Rett syndrome. Sequence homology for p.385-388delPLPP mutation revealed that these 4 amino acids were conserved across mammalian species. This indicated the importance of these 4 amino acids in structure and function of the protein. A novel variant p.T479T has also been identified in a patient with atypical Rett syndrome. A total of 62 (69%) patients remained without molecular genetics diagnosis that necessitates further search for mutations in other genes like CDKL5 and FOXG1 that are known to cause Rett phenotype. The majority of mutations are detected in exon 4 and only one mutation was present in exon 3. Therefore, our study suggests the need for screening exon 4 of MECP2 as first line of diagnosis in these patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. MECP2 gene study in a large cohort: testing of 240 female patients and 861 healthy controls (519 females and 342 males).

    Science.gov (United States)

    Maortua, Hiart; Martínez-Bouzas, Cristina; García-Ribes, Ainhoa; Martínez, María-Jesus; Guillen, Encarna; Domingo, María-Rosario; Calvo, María-Teresa; Guitart, Miriam; Gabau, Elisabeth; Botella, María-Pilar; Gener, Blanca; Rubio, Izaskun; López-Aríztegui, María-Asunción; Tejada, María-Isabel

    2013-09-01

    The MECP2 gene located on Xq28 is one of the most important genes contributing to the spectrum of neurodevelopmental disorders. Therefore, we present our experience in the molecular study of this gene. MECP2 was thoroughly tested for the presence of mutations (sequencing of four exons and rearrangements) in 120 female patients: 28 with classic Rett syndrome, five with atypical Rett syndrome, and 87 with heterogeneous phenotypes with some Rett-like features. Another 120 female patients with intellectual disability of unknown origin were also studied, but in these cases we only tested exons 3 and 4. Finally, 861 healthy controls (519 females and 342 males) were also studied for exon 3 and 4. Eighteen different pathological mutations were found, five of them previously undescribed, and four large deletions detected by multiplex ligation-dependent probe amplification. All were de novo mutations not present in the parents. In conclusion, i) MECP2 is one of the most important genes in the diagnosis of genetic intellectual disability in females; ii) MECP2 must be studied not only in patients with classical/atypical Rett syndrome but also in patients with other phenotypes related to Rett syndrome; and iii) for the new variants, it is important to perform complementary studies, including the analysis of large populations of healthy individuals and the use of in silico programs. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  13. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome

    NARCIS (Netherlands)

    Schonewolf-Greulich, B.; Tejada, M.I.; Stephens, K.; Hadzsiev, K.; Gauthier, J.; Brondum-Nielsen, K.; Pfundt, R.P.; Ravn, K.; Maortua, H.; Gener, B.; Martinez-Bouzas, C.; Piton, A.; Rouleau, G.; Clayton-Smith, J.; Kleefstra, T.; Bisgaard, A.M.; Tumer, Z.

    2016-01-01

    Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair

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

    NARCIS (Netherlands)

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

    Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder ( ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor

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

    NARCIS (Netherlands)

    Witteveen, J.S.; Willemsen, M.H.; Dombroski, T.C.; Bakel, N.H. van; Nillesen, W.M.; Hulten, J.A. van; Jansen, E.J.; Verkaik, D.; Veenstra-Knol, H.E.; Ravenswaaij-Arts, C.M.A. van; Wassink-Ruiter, J.S.; Vincent, M.; David, A.; Le Caignec, C.; Schieving, J.; Gilissen, C.; Foulds, N.; Rump, P.; Strom, T.; Cremer, K.; Zink, A.M.; Engels, H.; Munnik, S.A. de; Visser, J.E.; Brunner, H.G.; Martens, G.J.; Pfundt, R.P.; Kleefstra, T.; Kolk, S.M.

    2016-01-01

    Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor

  16. Mecp2 deficiency leads to altered Htr2c pre-mRNA editing and HTR2C isoform distribution in mouse hippocampus and cerebellum

    Science.gov (United States)

    Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, a methyl-CpG binding protein and transcriptional repressor. CpG methylation plays an important role in genomic imprinting since imprinted genes are regulated by regions of differentially methylated CpGs (or ICs). A ...

  17. Anaplerotic Triheptanoin Diet Enhances Mitochondrial Substrate Use to Remodel the Metabolome and Improve Lifespan, Motor Function, and Sociability in MeCP2-Null Mice

    Science.gov (United States)

    Li, Qun; Degano, Alicia L.; Penati, Judith; Zhuo, Justin; Roe, Charles R.; Ronnett, Gabriele V.

    2014-01-01

    Rett syndrome (RTT) is an autism spectrum disorder (ASD) caused by mutations in the X-linked MECP2 gene that encodes methyl-CpG binding protein 2 (MeCP2). Symptoms range in severity and include psychomotor disabilities, seizures, ataxia, and intellectual disability. Symptom onset is between 6-18 months of age, a critical period of brain development that is highly energy-dependent. Notably, patients with RTT have evidence of mitochondrial dysfunction, as well as abnormal levels of the adipokines leptin and adiponectin, suggesting overall metabolic imbalance. We hypothesized that one contributor to RTT symptoms is energy deficiency due to defective nutrient substrate utilization by the TCA cycle. This energy deficit would lead to a metabolic imbalance, but would be treatable by providing anaplerotic substrates to the TCA cycle to enhance energy production. We show that dietary therapy with triheptanoin significantly increased longevity and improved motor function and social interaction in male mice hemizygous for Mecp2 knockout. Anaplerotic therapy in Mecp2 knockout mice also improved indicators of impaired substrate utilization, decreased adiposity, increased glucose tolerance and insulin sensitivity, decreased serum leptin and insulin, and improved mitochondrial morphology in skeletal muscle. Untargeted metabolomics of liver and skeletal muscle revealed increases in levels of TCA cycle intermediates with triheptanoin diet, as well as normalizations of glucose and fatty acid biochemical pathways consistent with the improved metabolic phenotype in Mecp2 knockout mice on triheptanoin. These results suggest that an approach using dietary supplementation with anaplerotic substrate is effective in improving symptoms and metabolic health in RTT. PMID:25299635

  18. A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections

    OpenAIRE

    Xu, Xiu; Xu, Qiong; Zhang, Ying; Zhang, Xiaodi; Cheng, Tianlin; Wu, Bingbing; Ding, Yanhua; Lu, Ping; Zheng, Jingjing; Zhang, Min; Qiu, Zilong; Yu, Xiang

    2012-01-01

    Abstract Background Autistic spectrum disorders (ASDs) are a family of neurodevelopmental disorders with strong genetic components. Recent studies have shown that copy number variations in dosage sensitive genes can contribute significantly to these disorders. One such gene is the transcription factor MECP2, whose loss of function in females results in Rett syndrome, while its duplication in males results in developmental delay and autism. Case presentation Here, we identified a Chinese famil...

  19. Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features.

    Science.gov (United States)

    Miguet, Marguerite; Faivre, Laurence; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Lefebvre, Mathilde; Thevenon, Julien; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Remerand, Ganaëlle; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Béri-Dexheimer, Mylène; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Guibaud, Laurent; Cormier-Daire, Valérie; Rio, Marlene; Bonnefont, Jean-Paul; Echenne, Bernard; Journel, Hubert; Burglen, Lydie; Chantot-Bastaraud, Sandrine; Bienvenu, Thierry; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Dieterich, Klaus; Devillard, Françoise; Lacombe, Didier; Philip, Nicole; Sigaudy, Sabine; Moncla, Anne; Missirian, Chantal; Badens, Catherine; Perreton, Nathalie; Thauvin-Robinet, Christel; AChro-Puce, Réseau; Pedespan, Jean-Michel; Rooryck, Caroline; Goizet, Cyril; Vincent-Delorme, Catherine; Duban-Bedu, Bénédicte; Bahi-Buisson, Nadia; Afenjar, Alexandra; Maincent, Kim; Héron, Delphine; Alessandri, Jean-Luc; Martin-Coignard, Dominique; Lesca, Gaëtan; Rossi, Massimiliano; Raynaud, Martine; Callier, Patrick; Mosca-Boidron, Anne-Laure; Marle, Nathalie; Coutton, Charles; Satre, Véronique; Caignec, Cédric Le; Malan, Valérie; Romana, Serge; Keren, Boris; Tabet, Anne-Claude; Kremer, Valérie; Scheidecker, Sophie; Vigouroux, Adeline; Lackmy-Port-Lis, Marilyn; Sanlaville, Damien; Till, Marianne; Carneiro, Maryline; Gilbert-Dussardier, Brigitte; Willems, Marjolaine; Van Esch, Hilde; Portes, Vincent Des; El Chehadeh, Salima

    2018-04-04

    The Xq28 duplication involving the MECP2 gene ( MECP2 duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitial MECP2 duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype of MECP2 duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Structural Effects of Some Relevant Missense Mutations on the MECP2-DNA Binding: A MD Study Analyzed by Rescore+, a Versatile Rescoring Tool of the VEGA ZZ Program.

    Science.gov (United States)

    Pedretti, Alessandro; Granito, Cinzia; Mazzolari, Angelica; Vistoli, Giulio

    2016-09-01

    DNA methylation plays key roles in mammalian cells and is modulated by a set of proteins which recognize symmetrically methylated nucleotides. Among them, the protein MECP2 shows multifunctional roles repressing and/or activating genes by binding to both methylated and unmethylated regions of the genome. The interest for this protein markedly increased from the observation that its mutations are the primary cause of Rett syndrome, a neurodevelopmental disorder which causes mental retardation in young females. Thus, the present study is aimed to investigate the effects of some of these known pathogenic missense mutations (i.e. R106Q, R106W, R111G, R133C and R133H) on the MECP2 folding and DNA binding by molecular dynamics simulations. The effects of the simulated mutations are also parameterized by using a here proposed new tool, named Rescore+, implemented in the VEGA ZZ suite of programs, which calculates a set of scoring functions on all frames of a trajectory or on all complexes contained in a database thus allowing an easy rescoring of results coming from MD or docking simulations. The obtained results revealed that the reported loss of the MECP2 function induced by the simulated mutations can be ascribed to both stabilizing and destabilizing effect on DNA binding. The study confirms that MD simulations are particularly useful to rationalize and predict the mutation effects offering insightful information for diagnostics and drug design. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Expanding phenotype of p.Ala140Val mutation in MECP2 in a 4 generation family with X-linked intellectual disability and spasticity.

    Science.gov (United States)

    Lambert, Sophie; Maystadt, Isabelle; Boulanger, Sébastien; Vrielynck, Pascal; Destrée, Anne; Lederer, Damien; Moortgat, Stéphanie

    2016-10-01

    Mutations in MECP2 (MIM #312750), located on Xq28 and encoding a methyl CpG binding protein, are classically associated with Rett syndrome in female patients, with a lethal effect in hemizygous males. However, MECP2 mutations have already been reported in surviving males with severe neonatal-onset encephalopathy, or with X-linked intellectual disability associated with psychosis, pyramidal signs, parkinsonian features and macro-orchidism (PPM-X syndrome; MIM3 #300055). Here we report on the identification of the p.Ala140Val mutation in the MECP2 gene in 4 males and 3 females of a large Caucasian family affected with X-linked intellectual disability. Females present with mild cognitive impairment and speech difficulties. Males have moderate intellectual disability, impaired language development, friendly behavior, slowly progressive spastic paraparesis and dystonic movements of the hands. Two of them show microcephaly. The p.Ala140Val mutation is recurrent, as it was already described in 4 families with X-linked mental retardation and in three sporadic male patients with intellectual disability. We further delineate the phenotype associated with the p.Ala140Val mutation, illustrating a variable expressivity even within a given family, and we compare our patients with previous reported cases in the literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Kynurenine pathway metabolism following prenatal KMO inhibition and in Mecp2+/- mice, using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Forrest, Caroline M; Kennedy, Peter G E; Rodgers, Jean; Dalton, R Neil; Turner, Charles; Darlington, L Gail; Cobb, Stuart R; Stone, Trevor W

    2016-11-01

    To quantify the full range of tryptophan metabolites along the kynurenine pathway, a liquid chromatography - tandem mass spectrometry method was developed and used to analyse brain extracts of rodents treated with the kynurenine-3-mono-oxygenase (KMO) inhibitor Ro61-8048 during pregnancy. There were significant increases in the levels of kynurenine, kynurenic acid, anthranilic acid and 3-hydroxy-kynurenine (3-HK) in the maternal brain after 5 h but not 24 h, while the embryos exhibited high levels of kynurenine, kynurenic acid and anthranilic acid after 5 h which were maintained at 24 h post-treatment. At 24 h there was also a strong trend to an increase in quinolinic acid levels (P = 0.055). No significant changes were observed in any of the other kynurenine metabolites. The results confirm the marked increase in the accumulation of some neuroactive kynurenines when KMO is inhibited, and re-emphasise the potential importance of changes in anthranilic acid. The prolonged duration of metabolite accumulation in the embryo brains indicates a trapping of compounds within the embryonic CNS independently of maternal levels. When brains were examined from young mice heterozygous for the meCP2 gene - a potential model for Rett syndrome - no differences were noted from control mice, suggesting that the proposed roles for kynurenines in autism spectrum disorder are not relevant to Rett syndrome, supporting its recognition as a distinct, independent, condition. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Candace R. Lewis

    2013-06-01

    Full Text Available The maternal separation (MS paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH causes great harm to both the individual user and to society; yet, no studies have examined the effects of MS on METH SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2 in the nucleus accumbens (NAc core were also investigated. Long-Evans pups and dams were separated on postnatal days (PND 2-14 for either 180 (MS180 or 15 min (MS15. Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion in 15 2-hr daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

  4. Touchscreen learning deficits in Ube3a, Ts65Dn and Mecp2 mouse models of neurodevelopmental disorders with intellectual disabilities.

    Science.gov (United States)

    Leach, P T; Crawley, J N

    2017-12-20

    Mutant mouse models of neurodevelopmental disorders with intellectual disabilities provide useful translational research tools, especially in cases where robust cognitive deficits are reproducibly detected. However, motor, sensory and/or health issues consequent to the mutation may introduce artifacts that preclude testing in some standard cognitive assays. Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds. Here we use touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of Angelman syndrome, the Ts65Dn trisomy mouse model of Down syndrome, and the Mecp2 Bird mouse model of Rett syndrome. Significant deficits in acquisition of a 2-choice visual discrimination task were detected in both Ube3a and Ts65Dn mice. Procedural control measures showed no genotype differences during pretraining phases or during acquisition. Mecp2 males did not survive long enough for touchscreen training, consistent with previous reports. Most Mecp2 females failed on pretraining criteria. Significant impairments on Morris water maze spatial learning were detected in both Ube3a and Ts65Dn, replicating previous findings. Abnormalities on rotarod in Ube3a, and on open field in Ts65Dn, replicating previous findings, may have contributed to the observed acquisition deficits and swim speed abnormalities during water maze performance. In contrast, these motor phenotypes do not appear to have affected touchscreen procedural abilities during pretraining or visual discrimination training. Our findings of slower touchscreen learning in 2 mouse models of neurodevelopmental disorders with intellectual disabilities indicate that operant tasks offer promising outcome measures for the preclinical discovery of effective pharmacological therapeutics. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. Repression of TSC1/TSC2 mediated by MeCP2 regulates human embryo lung fibroblast cell differentiation and proliferation.

    Science.gov (United States)

    Wang, Yuanyuan; Chen, Chen; Deng, Ziyu; Bian, Erbao; Huang, Cheng; Lei, Ting; Lv, Xiongwen; Liu, Liping; Li, Jun

    2017-03-01

    Pulmonary fibrosis (PF) is a severe inflammatory disease with limited effective treatments. It is known that the transdifferentiation of human embryo lung fibroblast (HELF) cells from pulmonary fibroblasts into myofibroblasts, contributes to the progression of pulmonary fibrogenesis. The tuberous sclerosis proteins TSC1 and TSC2 are two key signaling factors which can suppress cell growth and proliferation. However, the roles of TSC1 and TSC2 in lung fibroblast are unclear. Here, we developed a PF model with bleomycin (BLM) in mice and conducted several simulation experiments in HELF cells. Our study shows that the expression of TSC1 and TSC2 in fibrotic mice lung was reduced and stimulation of HELF cells with TGF-β1 resulted in a down-regulation of TSC1 and TSC2. In addition, overexpression of TSC1 or TSC2 decreased cell proliferation and differentiation. Furthermore, we found that reduced expression of TSC1 and TSC2 caused by TGF-β1 is associated with the promoter methylation status of TSC1 and TSC2. MeCP2, controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis. We found that expression of TSC1 and TSC2 can be repressed by MeCP2, which regulates HELF cell differentiation and proliferation as myofibroblasts and lead to PF ultimately. Copyright © 2016. Published by Elsevier B.V.

  6. Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex

    Directory of Open Access Journals (Sweden)

    Rocco Piazza

    2013-05-01

    Full Text Available BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2 corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

  7. The study on morphologic alteration of fetal mice and the change of MeCP2 in fetal brain induced by ionizing radiation

    International Nuclear Information System (INIS)

    Chen Feng; Zhang Fengxiang; Tu Yu

    2012-01-01

    Objective: In order to investigate the effect and the possible mechanism of γ-rays on neuro development of fetal brain tissue as bystander effect organ. Methods: pregnant kunming mice were randomly divided into blank control group, 0.5 Gy whole-body exposed group, 0.5 Gy head exposed group, 1.0 Gy whole-body exposed group, 1.0 Gy head exposed group, 2.0 Gy whole-body exposed group and 2.0 Gy head exposed group. The exposed mice were exposed with a vertical single acute dose using 60 Co therapy apparatus on the 9 th day of pregnancy, and cesarean operation were performed to gain fetal mice on the 18 th day of pregnancy. The number, the size, stillbirth, birth defects and abortion, and get fetal brains from live births were observed. Western-blot assay was used to detect the expression of MeCP2 protein. Results: Compared with the blank control group, the rates of stillbirth, birth defects and abortion ascended as the increase of doses; the expression of MeCP2 were upregulated except 0.5 Gy whole-body exposed group, there were no significant differences between groups. Conclusion: When the pregnant mice were exposed to ionizing radiation in the first trimester, bystander effect in fetal brain tissue was induced, within a certain range, the incidence of deterministic effects and stochastic effects ascended as the increase of doses. (authors)

  8. Therapeutic Interference With Vascular Calcification—Lessons From Klotho-Hypomorphic Mice and Beyond

    Directory of Open Access Journals (Sweden)

    Florian Lang

    2018-05-01

    Full Text Available Medial vascular calcification, a major pathophysiological process associated with cardiovascular disease and mortality, involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs. In chronic kidney disease (CKD, osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification is mainly driven by hyperphosphatemia, resulting from impaired elimination of phosphate by the diseased kidneys. Hyperphosphatemia with subsequent vascular calcification is a hallmark of klotho-hypomorphic mice, which are characterized by rapid development of multiple age-related disorders and early death. In those animals, hyperphosphatemia results from unrestrained formation of 1,25(OH2D3 with subsequent retention of calcium and phosphate. Analysis of klotho-hypomorphic mice and mice with vitamin D3 overload uncovered several pathophysiological mechanisms participating in the orchestration of vascular calcification and several therapeutic opportunities to delay or even halt vascular calcification. The present brief review addresses the beneficial effects of bicarbonate, carbonic anhydrase inhibition, magnesium supplementation, mineralocorticoid receptor (MR blockage, and ammonium salts. The case is made that bicarbonate is mainly effective by decreasing intestinal phosphate absorption, and that carbonic anhydrase inhibition leads to metabolic acidosis, which counteracts calcium-phosphate precipitation and VSMC transdifferentiation. Magnesium supplementation, MR blockage and ammonium salts are mainly effective by interference with osteo-/chondrogenic signaling in VSMCs. It should be pointed out that the, by far, most efficient substances are ammonium salts, which may virtually prevent vascular calcification. Future research will probably uncover further therapeutic options and, most importantly, reveal whether these observations in mice can be translated into treatment of patients suffering from vascular calcification, such

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

    Science.gov (United States)

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

    2016-08-01

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

  10. Progressive cerebellar degenerative changes in the severe mental retardation syndrome caused by duplication of MECP2 and adjacent loci on Xq28.

    LENUS (Irish Health Repository)

    Reardon, William

    2010-08-01

    Localised duplications, involving the MECP2 locus, at Xq28 have been associated with a syndrome comprising X-linked mental retardation, hypotonia and recurrent infections in males. We now present neuroradiological evidence that progressive cerebellar degenerative changes may also be a consistent feature of this syndrome, emerging in the second decade of life. We report seven affected males, from three different families who, in addition to the previously described clinical findings, have a reduction in the volume of the white matter and mild dilatation of the lateral ventricles. Three of the older patients show a consistent cerebellar degenerative phenotype. Furthermore, we describe the first female affected with the disorder. The female was mildly affected and shows X-inactivation in the ratio of 70:30, demonstrating that X-inactivation cannot be exclusively relied upon to spare the female carriers from symptoms. In conclusion, there is a radiological phenotype associated with Xq28 duplication which clearly demonstrates progressive degenerative cerebellar disease as part of the syndrome.

  11. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

    Science.gov (United States)

    Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

    2016-06-01

    Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction: Atomistic characterization of a Rett syndrome causing mutation.

    Science.gov (United States)

    D'Annessa, Ilda; Gandaglia, Anna; Brivio, Elena; Stefanelli, Gilda; Frasca, Angelisa; Landsberger, Nicoletta; Di Marino, Daniele

    2018-05-01

    Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies. Herein, we use molecular dynamics simulations to obtain a detailed view of the dynamics of WT and mutated MBD in the presence and absence of DNA. The pathogenic mutation Y120D is used as paradigm for our studies. Further, since the Y120 residue was previously found to be a phosphorylation site, we characterize the dynamic profile of the MBD also in the presence of Y120 phosphorylation (pY120). We found that addition of a phosphate group to Y120 or mutation in aspartic acid affect domain mobility that samples an alternative conformational space with respect to the WT, leading to impaired ability to interact with DNA. Experimental assays showing a significant reduction in the binding affinity between the mutated MBD and the DNA confirmed our predictions. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Prolonged Ketamine Effects in Sp4 Hypomorphic Mice: Mimicking Phenotypes of Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Baohu Ji

    Full Text Available It has been well established that schizophrenia patients display impaired NMDA receptor (NMDAR functions as well as exacerbation of symptoms in response to NMDAR antagonists. Abnormal NMDAR signaling presumably contributes to cognitive deficits which substantially contribute to functional disability in schizophrenia. Establishing a mouse genetic model will help investigate molecular mechanisms of hypoglutmatergic neurotransmission in schizophrenia. Here, we examined the responses of Sp4 hypomorphic mice to NMDAR antagonists in electroencephalography and various behavioral paradigms. Sp4 hypomorphic mice, previously reported to have reduced NMDAR1 expression and LTP deficit in hippocampal CA1, displayed increased sensitivity and prolonged responses to NMDAR antagonists. Molecular studies demonstrated reduced expression of glutamic acid decarboxylase 67 (GAD67 in both cortex and hippocampus, consistent with abnormal gamma oscillations in Sp4 hypomorphic mice. On the other hand, human SP4 gene was reported to be deleted in schizophrenia. Several human genetic studies suggested the association of SP4 gene with schizophrenia and other psychiatric disorders. Therefore, elucidation of the Sp4 molecular pathway in Sp4 hypomorphic mice may provide novel insights to our understanding of abnormal NMDAR signaling in schizophrenia.

  14. Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

    Science.gov (United States)

    Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

    2013-03-15

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

  15. Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

    Science.gov (United States)

    KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael

    2016-03-01

    Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

  16. Genetics Home Reference: MECP2 duplication syndrome

    Science.gov (United States)

    ... and Stroke: Seizures and Epilepsy National Institute of Neurological Disorders and Stroke: Spasticity Information Page Educational Resources (6 links) Boston Children's Hospital: Respiratory Distress Boston Children's Hospital: Seizures Centers ...

  17. EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele.

    Science.gov (United States)

    Rein, Katrin; Yanez, Diana A; Terré, Berta; Palenzuela, Lluís; Aivio, Suvi; Wei, Kaichun; Edelmann, Winfried; Stark, Jeremy M; Stracker, Travis H

    2015-09-03

    The maintenance of genome stability is critical for the suppression of diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. The DNA damage response (DDR) orchestrates the appropriate cellular responses following the detection of lesions to prevent genomic instability. The MRE11 complex is a sensor of DNA double strand breaks (DSBs) and plays key roles in multiple aspects of the DDR, including DNA end resection that is critical for signaling and DNA repair. The MRE11 complex has been shown to function both upstream and in concert with the 5'-3' exonuclease EXO1 in DNA resection, but it remains unclear to what extent EXO1 influences DSB responses independently of the MRE11 complex. Here we examine the genetic relationship of the MRE11 complex and EXO1 during mammalian development and in response to DNA damage. Deletion of Exo1 in mice expressing a hypomorphic allele of Nbs1 leads to severe developmental impairment, embryonic death and chromosomal instability. While EXO1 plays a minimal role in normal cells, its loss strongly influences DNA replication, DNA repair, checkpoint signaling and damage sensitivity in NBS1 hypomorphic cells. Collectively, our results establish a key role for EXO1 in modulating the severity of hypomorphic MRE11 complex mutations. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

    Science.gov (United States)

    Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

    2015-10-01

    NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Novel Hypomorphic Mutation in FANCD2 Gene Observed in a Fetus with Multiple Congenital Anomalies

    Directory of Open Access Journals (Sweden)

    Radoslava Vazharova

    2016-01-01

    Full Text Available Congenital anomalies affect 1% to 2% of the newborns. The urinary tract and the kidneys are involved in 4-5% of the cases while upper-extremities abnormalities are present in 10%. Certain anomalies occur in isolation, whereas others are associated with systemic conditions. The prenatal detection of fetal anomalies compatible with life is a challenge for both the parents and the physician. The prognosis for the fetus/newborn and the reproductive decisions of the family largely depend on the causes underlying the disease. The reported case is of a G2P1 pregnant woman referred for routine ultrasound scan at 24 weeks of gestation (w.g.. The fetus had growth retardation, right kidney agenesis, bilateral absence of radial bones and thumbs, radial deviation of the wrists, and short humeri. Nuchal fold thickness was 5 mm and there was a single umbilical artery. After termination of pregnancy, SNP array genotyping and next-generation sequencing of targeted candidate-genes were performed trying to clarify the etiology of the fetal polymalformative syndrome. A new hypomorphic mutation in FANCD2 gene was found to underlie this fetal anomaly. The case illustrates that patients/families affected by rare monogenic disorders may benefit from application of modern technologies like microarrays and NGS.

  20. Hypomorphic mutation in mouse Nppc gene causes retarded bone growth due to impaired endochondral ossification

    International Nuclear Information System (INIS)

    Tsuji, Takehito; Kondo, Eri; Yasoda, Akihiro; Inamoto, Masataka; Kiyosu, Chiyo; Nakao, Kazuwa; Kunieda, Tetsuo

    2008-01-01

    Long bone abnormality (lbab/lbab) is a spontaneous mutant mouse characterized by dwarfism with shorter long bones. A missense mutation was reported in the Nppc gene, which encodes C-type natriuretic peptide (CNP), but it has not been confirmed whether this mutation is responsible for the dwarf phenotype. To verify that the mutation causes the dwarfism of lbab/lbab mice, we first investigated the effect of CNP in lbab/lbab mice. By transgenic rescue with chondrocyte-specific expression of CNP, the dwarf phenotype in lbab/lbab mice was completely compensated. Next, we revealed that CNP derived from the lbab allele retained only slight activity to induce cGMP production through its receptor. Histological analysis showed that both proliferative and hypertrophic zones of chondrocytes in the growth plate of lbab/lbab mice were markedly reduced. Our results demonstrate that lbab/lbab mice have a hypomorphic mutation in the Nppc gene that is responsible for dwarfism caused by impaired endochondral ossification

  1. A Hypomorphic PALB2 Allele Gives Rise to an Unusual Form of FA-N Associated with Lymphoid Tumour Development.

    Directory of Open Access Journals (Sweden)

    Philip J Byrd

    2016-03-01

    Full Text Available Patients with biallelic truncating mutations in PALB2 have a severe form of Fanconi anaemia (FA-N, with a predisposition for developing embryonal-type tumours in infancy. Here we describe two unusual patients from a single family, carrying biallelic PALB2 mutations, one truncating, c.1676_1677delAAinsG;(p.Gln559ArgfsTer2, and the second, c.2586+1G>A; p.Thr839_Lys862del resulting in an in frame skip of exon 6 (24 amino acids. Strikingly, the affected individuals did not exhibit the severe developmental defects typical of FA-N patients and initially presented with B cell non-Hodgkin lymphoma. The expressed p.Thr839_Lys862del mutant PALB2 protein retained the ability to interact with BRCA2, previously unreported in FA-N patients. There was also a large increased chromosomal radiosensitivity following irradiation in G2 and increased sensitivity to mitomycin C. Although patient cells were unable to form Rad51 foci following exposure to either DNA damaging agent, U2OS cells, in which the mutant PALB2 with in frame skip of exon 6 was induced, did show recruitment of Rad51 to foci following damage. We conclude that a very mild form of FA-N exists arising from a hypomorphic PALB2 allele.

  2. Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology

    International Nuclear Information System (INIS)

    Shafey, Dina; Cote, Patrice D.; Kothary, Rashmi

    2005-01-01

    Dosage of the survival motor neuron (SMN) protein has been directly correlated with the severity of disease in patients diagnosed with spinal muscular atrophy (SMA). It is also clear that SMA is a neurodegenerative disorder characterized by the degeneration of the α-motor neurons in the anterior horn of the spinal cord and atrophy of the associated skeletal muscle. What is more controversial is whether it is neuronal and/or muscle-cell-autonomous defects that are responsible for the disease per se. Although motor neuron degeneration is generally accepted as the primary event in SMA, intrinsic muscle defects in this disease have not been ruled out. To gain a better understanding of the influence of SMN protein dosage in muscle, we have generated a hypomorphic series of myoblast (C2C12) stable cell lines with variable Smn knockdown. We show that depletion of Smn in these cells resulted in a decrease in the number of nuclear 'gems' (gemini of coiled bodies), reduced proliferation with no increase in cell death, defects in myoblast fusion, and malformed myotubes. Importantly, the severity of these abnormalities is directly correlated with the decrease in Smn dosage. Taken together, our work supports the view that there is an intrinsic defect in skeletal muscle cells of SMA patients and that this defect contributes to the overall pathogenesis in this devastating disease

  3. Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice.

    Directory of Open Access Journals (Sweden)

    Jarrah R Spencer

    2013-02-01

    Full Text Available Neuregulin 1 (NRG1 is linked to an increased risk of developing schizophrenia and cannabis dependence. Mice that are hypomorphic for Nrg1 (Nrg1 HET mice display schizophrenia-relevant behavioural phenotypes and aberrant expression of serotonin and glutamate receptors. Nrg1 HET mice also display idiosyncratic responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol (THC. To gain traction on the molecular pathways disrupted by Nrg1 hypomorphism and Nrg1-cannabinoid interactions we conducted a proteomic study. Adolescent wildtype (WT and Nrg1 HET mice were exposed to repeated injections of vehicle or THC and their hippocampi were submitted to 2D gel proteomics. Comparison of WT and Nrg1 HET mice identified proteins linked to molecular changes in schizophrenia that have not been previously associated with Nrg1. These proteins are involved in vesicular release of neurotransmitters such as SNARE proteins; enzymes impacting serotonergic neurotransmission, and; proteins affecting growth factor expression. Nrg1 HET mice treated with THC expressed a distinct protein expression signature compared to WT mice. Replicating prior findings, THC caused proteomic changes in WT mice suggestive of greater oxidative stress and neurodegeneration. We have previously observed that THC selectively increased hippocampal NMDA receptor binding of adolescent Nrg1 HET mice. Here we observed outcomes consistent with heightened NMDA-mediated glutamatergic neurotransmission. This included differential expression of proteins involved in NMDA receptor trafficking to the synaptic membrane; lipid raft stabilization of synaptic NMDA receptors; and homeostatic responses to dampen excitotoxicity. These findings uncover for the first time novel proteins altered in response to Nrg1 hypomorphism and Nrg1-cannabinoid interactions that improves our molecular understanding of Nrg1 signaling and Nrg1-mediated genetic vulnerability to the neurobehavioural effects

  4. Genetics Home Reference: MECP2-related severe neonatal encephalopathy

    Science.gov (United States)

    ... and Stroke: Encephalopathy Information Page National Institute of Neurological Disorders and Stroke: Microcephaly Information Page Educational Resources (8 links) Boston Children's Hospital: Seizures Centers for Disease Control and Prevention: ...

  5. Compound heterozygosity of the functionally null Cdh23(v-ngt) and hypomorphic Cdh23(ahl) alleles leads to early-onset progressive hearing loss in mice.

    Science.gov (United States)

    Miyasaka, Yuki; Suzuki, Sari; Ohshiba, Yasuhiro; Watanabe, Kei; Sagara, Yoshihiko; Yasuda, Shumpei P; Matsuoka, Kunie; Shitara, Hiroshi; Yonekawa, Hiromichi; Kominami, Ryo; Kikkawa, Yoshiaki

    2013-01-01

    The waltzer (v) mouse mutant harbors a mutation in Cadherin 23 (Cdh23) and is a model for Usher syndrome type 1D, which is characterized by congenital deafness, vestibular dysfunction, and prepubertal onset of progressive retinitis pigmentosa. In mice, functionally null Cdh23 mutations affect stereociliary morphogenesis and the polarity of both cochlear and vestibular hair cells. In contrast, the murine Cdh23(ahl) allele, which harbors a hypomorphic mutation, causes an increase in susceptibility to age-related hearing loss in many inbred strains. We produced congenic mice by crossing mice carrying the v niigata (Cdh23(v-ngt)) null allele with mice carrying the hypomorphic Cdh23(ahl) allele on the C57BL/6J background, and we then analyzed the animals' balance and hearing phenotypes. Although the Cdh23(v-ngt/ahl) compound heterozygous mice exhibited normal vestibular function, their hearing ability was abnormal: the mice exhibited higher thresholds of auditory brainstem response (ABR) and rapid age-dependent elevation of ABR thresholds compared with Cdh23(ahl/ahl) homozygous mice. We found that the stereocilia developed normally but were progressively disrupted in Cdh23(v-ngt/ahl) mice. In hair cells, CDH23 localizes to the tip links of stereocilia, which are thought to gate the mechanoelectrical transduction channels in hair cells. We hypothesize that the reduction of Cdh23 gene dosage in Cdh23(v-ngt/ahl) mice leads to the degeneration of stereocilia, which consequently reduces tip link tension. These findings indicate that CDH23 plays an important role in the maintenance of tip links during the aging process.

  6. PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres in murine embryonic stem cells.

    Science.gov (United States)

    Reynolds, Gloria E; Gao, Qing; Miller, Douglas; Snow, Bryan E; Harrington, Lea A; Murnane, John P

    2011-11-10

    Telomerase serves to maintain telomeric repeat sequences at the ends of chromosomes. However, telomerase can also add telomeric repeat sequences at DNA double-strand breaks (DSBs), a process called chromosome healing. Here, we employed a method of inducing DSBs near telomeres to query the role of two proteins, PIF1 and NBS1, in chromosome healing in mammalian cells. PIF1 was investigated because the PIF1 homolog in Saccharomyces cerevisiae inhibits chromosome healing, as shown by a 1000-fold increase in chromosome in PIF1-deficient cells. NBS1 was investigated because the functional homolog of NBS1 in S. cerevisiae, Xrs2, is part of the Mre11/Rad50/Xrs2 complex that is required for chromosome healing due to its role in the processing of DSBs and recruitment of telomerase. We found that disruption of mPif1 had no detectable effect on the frequency of chromosome healing at DSBs near telomeres in murine embryonic stem cells. Moreover, the Nbs1(ΔB) hypomorph, which is defective in the processing of DSBs, also had no detectable effect on the frequency of chromosome healing, DNA degradation, or gross chromosome rearrangements (GCRs) that result from telomeric DSBs. Although we cannot rule out small changes in chromosome healing using this system, it is clear from our results that knockout of PIF1 or the Nbs1(ΔB) hypomorph does not result in large differences in chromosome healing in murine cells. These results represent the first genetic assessment of the role of these proteins in chromosome healing in mammals, and suggest that murine cells have evolved mechanisms to ensure the functional redundancy of Pif1 or Nbs1 in the regulation of chromosome healing. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Novel Hypomorphic Alleles of the Mouse Tyrosinase Gene Induced by CRISPR-Cas9 Nucleases Cause Non-Albino Pigmentation Phenotypes.

    Science.gov (United States)

    Challa, Anil K; Boitet, Evan R; Turner, Ashley N; Johnson, Larry W; Kennedy, Daniel; Downs, Ethan R; Hymel, Katherine M; Gross, Alecia K; Kesterson, Robert A

    2016-01-01

    Tyrosinase is a key enzyme in melanin biosynthesis. Mutations in the gene encoding tyrosinase (Tyr) cause oculocutaneous albinism (OCA1) in humans. Alleles of the Tyr gene have been useful in studying pigment biology and coat color formation. Over 100 different Tyr alleles have been reported in mice, of which ≈24% are spontaneous mutations, ≈60% are radiation-induced, and the remaining alleles were obtained by chemical mutagenesis and gene targeting. Therefore, most mutations were random and could not be predicted a priori. Using the CRISPR-Cas9 system, we targeted two distinct regions of exon 1 to induce pigmentation changes and used an in vivo visual phenotype along with heteroduplex mobility assays (HMA) as readouts of CRISPR-Cas9 activity. Most of the mutant alleles result in complete loss of tyrosinase activity leading to an albino phenotype. In this study, we describe two novel in-frame deletion alleles of Tyr, dhoosara (Sanskrit for gray) and chandana (Sanskrit for sandalwood). These alleles are hypomorphic and show lighter pigmentation phenotypes of the body and eyes. This study demonstrates the utility of CRISPR-Cas9 system in generating domain-specific in-frame deletions and helps gain further insights into structure-function of Tyr gene.

  8. Novel Hypomorphic Alleles of the Mouse Tyrosinase Gene Induced by CRISPR-Cas9 Nucleases Cause Non-Albino Pigmentation Phenotypes.

    Directory of Open Access Journals (Sweden)

    Anil K Challa

    Full Text Available Tyrosinase is a key enzyme in melanin biosynthesis. Mutations in the gene encoding tyrosinase (Tyr cause oculocutaneous albinism (OCA1 in humans. Alleles of the Tyr gene have been useful in studying pigment biology and coat color formation. Over 100 different Tyr alleles have been reported in mice, of which ≈24% are spontaneous mutations, ≈60% are radiation-induced, and the remaining alleles were obtained by chemical mutagenesis and gene targeting. Therefore, most mutations were random and could not be predicted a priori. Using the CRISPR-Cas9 system, we targeted two distinct regions of exon 1 to induce pigmentation changes and used an in vivo visual phenotype along with heteroduplex mobility assays (HMA as readouts of CRISPR-Cas9 activity. Most of the mutant alleles result in complete loss of tyrosinase activity leading to an albino phenotype. In this study, we describe two novel in-frame deletion alleles of Tyr, dhoosara (Sanskrit for gray and chandana (Sanskrit for sandalwood. These alleles are hypomorphic and show lighter pigmentation phenotypes of the body and eyes. This study demonstrates the utility of CRISPR-Cas9 system in generating domain-specific in-frame deletions and helps gain further insights into structure-function of Tyr gene.

  9. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Science.gov (United States)

    Kuzin, Boris A; Nikitina, Ekaterina A; Cherezov, Roman O; Vorontsova, Julia E; Slezinger, Mikhail S; Zatsepina, Olga G; Simonova, Olga B; Enikolopov, Grigori N; Savvateeva-Popova, Elena V

    2014-01-01

    Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  10. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Directory of Open Access Journals (Sweden)

    Boris A Kuzin

    Full Text Available Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  11. Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase

    International Nuclear Information System (INIS)

    Gao Hong; Coyle, Donna L.; Meyer-Ficca, Mirella L.; Meyer, Ralph G.; Jacobson, Elaine L.; Wang, Zhao-Qi; Jacobson, Myron K.

    2007-01-01

    Genotoxic stress activates nuclear poly(ADP-ribose) (PAR) metabolism leading to PAR synthesis catalyzed by DNA damage activated poly(ADP-ribose) polymerases (PARPs) and rapid PAR turnover by action of nuclear poly(ADP-ribose) glycohydrolase (PARG). The involvement of PARP-1 and PARP-2 in responses to DNA damage has been well studied but the involvement of nuclear PARG is less well understood. To gain insights into the function of nuclear PARG in DNA damage responses, we have quantitatively studied PAR metabolism in cells derived from a hypomorphic mutant mouse model in which exons 2 and 3 of the PARG gene have been deleted (PARG-Δ2,3 cells), resulting in a nuclear PARG containing a catalytic domain but lacking the N-terminal region (A domain) of the protein. Following DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), we found that the activity of both PARG and PARPs in intact cells is increased in PARG-Δ2,3 cells. The increased PARG activity leads to decreased PARP-1 automodification with resulting increased PARP activity. The degree of PARG activation is greater than PARP, resulting in decreased PAR accumulation. Following MNNG treatment, PARG-Δ2,3 cells show reduced formation of XRCC1 foci, delayed H2AX phosphorylation, decreased DNA break intermediates during repair, and increased cell death. Our results show that a precise coordination of PARPs and PARG activities is important for normal cellular responses to DNA damage and that this coordination is defective in the absence of the PARG A domain

  12. Late-Onset Non-HLH Presentations of Growth Arrest, Inflammatory Arachnoiditis, and Severe Infectious Mononucleosis, in Siblings with Hypomorphic Defects in UNC13D

    Directory of Open Access Journals (Sweden)

    Paul Edgar Gray

    2017-08-01

    Full Text Available Bi-allelic null mutations affecting UNC13D, STXBP2, or STX11 result in defects of lymphocyte cytotoxic degranulation and commonly cause familial hemophagocytic lymphohistiocytosis (FHL in early life. Patients with partial loss of function are increasingly being diagnosed after presenting with alternative features of this disease, or with HLH later in life. Here, we studied two sisters with lymphocyte degranulation defects secondary to compound heterozygote missense variants in UNC13D. The older sibling presented aged 11 with linear growth arrest and delayed puberty, 2 years prior to developing transient ischemic attacks secondary to neuroinflammation and hypogammaglobulinemia, but no FHL symptoms. Her geno-identical younger sister was initially asymptomatic but then presented at the same age with severe EBV-driven infectious mononucleosis, which was treated aggressively and did not progress to HLH. The sisters had similar natural killer cell degranulation; however, while cytotoxic activity was moderately reduced in the asymptomatic patient, it was completely absent in both siblings during active disease. Following allogeneic bone marrow transplantation at the age of 15, the older child has completely recovered NK cell cytotoxicity, is asymptomatic, and has experienced an exceptional compensatory growth spurt. Her younger sister was also successfully transplanted and is currently disease free. The current study reveals previously unappreciated manifestations of FHL in patients who inherited hypomorphic gene variants and also raises the important question of whether a threshold of minimum NK function can be defined that should protect a patient from serious disease manifestations such as HLH.

  13. Tipping Point

    Medline Plus

    Full Text Available ... en español Blog About OnSafety CPSC Stands for Safety The Tipping Point Home > 60 Seconds of Safety (Videos) > The Tipping Point The Tipping Point by ... danger death electrical fall furniture head injury product safety television tipover tv Watch the video in Adobe ...

  14. Fixed Points

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 5. Fixed Points - From Russia with Love - A Primer of Fixed Point Theory. A K Vijaykumar. Book Review Volume 5 Issue 5 May 2000 pp 101-102. Fulltext. Click here to view fulltext PDF. Permanent link:

  15. Tipping Point

    Medline Plus

    Full Text Available ... OnSafety CPSC Stands for Safety The Tipping Point Home > 60 Seconds of Safety (Videos) > The Tipping Point ... 24 hours a day. For young children whose home is a playground, it’s the best way to ...

  16. Tipping Point

    Medline Plus

    Full Text Available ... 60 Seconds of Safety (Videos) > The Tipping Point The Tipping Point by CPSC Blogger September 22, 2009 appliance child Childproofing CPSC danger death electrical fall furniture head injury product safety television tipover tv Watch the video in Adobe Flash ...

  17. Molecular analysis of MECP2 gene in Egyptian patients with Rett ...

    African Journals Online (AJOL)

    Maha S. Zaki

    2011-12-28

    Dec 28, 2011 ... criteria of the classic form and can be milder or more severe. The milder .... 4. Discussion. RTT is one of the most common causes of mental retardation .... social withdraw. 1. 1. 1. 1. 1. 1. 1 .... J Child Neurol 2010;25(7):842–8.

  18. Dew Point

    OpenAIRE

    Goldsmith, Shelly

    1999-01-01

    Dew Point was a solo exhibition originating at PriceWaterhouseCoopers Headquarters Gallery, London, UK and toured to the Centre de Documentacio i Museu Textil, Terrassa, Spain and Gallery Aoyama, Tokyo, Japan.

  19. Tipping Point

    Medline Plus

    Full Text Available ... Point by CPSC Blogger September 22, 2009 appliance child Childproofing CPSC danger death electrical fall furniture head injury product safety television tipover tv Watch the video in Adobe Flash ...

  20. Tipping Point

    Science.gov (United States)

    ... Point by CPSC Blogger September 22, 2009 appliance child Childproofing CPSC danger death electrical fall furniture head injury product safety television tipover tv Watch the video in Adobe Flash ...

  1. Tipping Point

    Medline Plus

    Full Text Available ... Point by CPSC Blogger September 22, 2009 appliance child Childproofing CPSC danger death electrical fall furniture head ... see news reports about horrible accidents involving young children and furniture, appliance and tv tip-overs. The ...

  2. Tipping Point

    Medline Plus

    Full Text Available ... Point by CPSC Blogger September 22, 2009 appliance child Childproofing CPSC danger death electrical fall furniture head ... TV falls with about the same force as child falling from the third story of a building. ...

  3. Tipping Point

    Medline Plus

    Full Text Available ... Tipping Point by CPSC Blogger September 22, 2009 appliance child Childproofing CPSC danger death electrical fall furniture ... about horrible accidents involving young children and furniture, appliance and tv tip-overs. The force of a ...

  4. The expression of spinal methyl-CpG-binding protein 2, DNA methyltransferases and histone deacetylases is modulated in persistent pain states

    Directory of Open Access Journals (Sweden)

    Tochiki Keri K

    2012-02-01

    Full Text Available Abstract Background DNA CpG methylation is carried out by DNA methyltransferases and induces chromatin remodeling and gene silencing through a transcription repressor complex comprising the methyl-CpG-binding protein 2 (MeCP2 and a subset of histone deacetylases. Recently, we have found that MeCP2 activity had a crucial role in the pattern of gene expression seen in the superficial dorsal horn rapidly after injection of Complete Freund's Adjuvant (CFA in the rat ankle joint. The aim of the present study was to analyse the changes in expression of MeCP2, DNA methyltransferases and a subset of histone deacetylases in the superficial dorsal horn during the maintenance phase of persistent pain states. In this process, the cell specific expression of MeCP2 was also investigated. Results Using immunohistochemistry, we found that neurones, oligodendrocytes and astrocytes expressed MeCP2. Microglia, oligodendrocyte precursor cells and Schwann cells never showed any positive stain for MeCP2. Quantitative analyses showed that MeCP2 expression was increased in the superficial dorsal horn 7 days following CFA injection in the ankle joint but decreased 7 days following spared nerve injury. Overall, the expression of DNA methyltransferases and a subset of histone deacetylases followed the same pattern of expression. However, there were no significant changes in the expression of the MeCP2 targets that we had previously shown are regulated in the early time points following CFA injection in the ankle joint. Finally, the expression of MeCP2 was also down regulated in damaged dorsal root ganglion neurones following spared nerve injury. Conclusion Our results strongly suggest that changes in chromatin compaction, regulated by the binding of MeCP2 complexes to methylated DNA, are involved in the modulation of gene expression in the superficial dorsal horn and dorsal root ganglia during the maintenance of persistent pain states.

  5. Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders

    Science.gov (United States)

    Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-functi...

  6. The End of Points

    Science.gov (United States)

    Feldman, Jo

    2018-01-01

    Have teachers become too dependent on points? This article explores educators' dependency on their points systems, and the ways that points can distract teachers from really analyzing students' capabilities and achievements. Feldman argues that using a more subjective grading system can help illuminate crucial information about students and what…

  7. Demerit points systems.

    NARCIS (Netherlands)

    2006-01-01

    In 2012, 21 of the 27 EU Member States had some form of demerit points system. In theory, demerit points systems contribute to road safety through three mechanisms: 1) prevention of unsafe behaviour through the risk of receiving penalty points, 2) selection and suspension of the most frequent

  8. Point specificity in acupuncture

    Directory of Open Access Journals (Sweden)

    Choi Emma M

    2012-02-01

    Full Text Available Abstract The existence of point specificity in acupuncture is controversial, because many acupuncture studies using this principle to select control points have found that sham acupoints have similar effects to those of verum acupoints. Furthermore, the results of pain-related studies based on visual analogue scales have not supported the concept of point specificity. In contrast, hemodynamic, functional magnetic resonance imaging and neurophysiological studies evaluating the responses to stimulation of multiple points on the body surface have shown that point-specific actions are present. This review article focuses on clinical and laboratory studies supporting the existence of point specificity in acupuncture and also addresses studies that do not support this concept. Further research is needed to elucidate the point-specific actions of acupuncture.

  9. Interesting Interest Points

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Dahl, Anders Lindbjerg; Pedersen, Kim Steenstrup

    2012-01-01

    on spatial invariance of interest points under changing acquisition parameters by measuring the spatial recall rate. The scope of this paper is to investigate the performance of a number of existing well-established interest point detection methods. Automatic performance evaluation of interest points is hard......Not all interest points are equally interesting. The most valuable interest points lead to optimal performance of the computer vision method in which they are employed. But a measure of this kind will be dependent on the chosen vision application. We propose a more general performance measure based...... position. The LED illumination provides the option for artificially relighting the scene from a range of light directions. This data set has given us the ability to systematically evaluate the performance of a number of interest point detectors. The highlights of the conclusions are that the fixed scale...

  10. Point defects in solids

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The principal properties of point defects are studied: thermodynamics, electronic structure, interactions with etended defects, production by irradiation. Some measuring methods are presented: atomic diffusion, spectroscopic methods, diffuse scattering of neutron and X rays, positron annihilation, molecular dynamics. Then points defects in various materials are investigated: ionic crystals, oxides, semiconductor materials, metals, intermetallic compounds, carbides, nitrides [fr

  11. Indexing Moving Points

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Arge, Lars Allan; Erickson, Jeff

    2003-01-01

    We propose three indexing schemes for storing a set S of N points in the plane, each moving along a linear trajectory, so that any query of the following form can be answered quickly: Given a rectangle R and a real value t, report all K points of S that lie inside R at time t. We first present an...

  12. Generalized zero point anomaly

    International Nuclear Information System (INIS)

    Nogueira, Jose Alexandre; Maia Junior, Adolfo

    1994-01-01

    It is defined Zero point Anomaly (ZPA) as the difference between the Effective Potential (EP) and the Zero point Energy (ZPE). It is shown, for a massive and interacting scalar field that, in very general conditions, the renormalized ZPA vanishes and then the renormalized EP and ZPE coincide. (author). 3 refs

  13. Poisson branching point processes

    International Nuclear Information System (INIS)

    Matsuo, K.; Teich, M.C.; Saleh, B.E.A.

    1984-01-01

    We investigate the statistical properties of a special branching point process. The initial process is assumed to be a homogeneous Poisson point process (HPP). The initiating events at each branching stage are carried forward to the following stage. In addition, each initiating event independently contributes a nonstationary Poisson point process (whose rate is a specified function) located at that point. The additional contributions from all points of a given stage constitute a doubly stochastic Poisson point process (DSPP) whose rate is a filtered version of the initiating point process at that stage. The process studied is a generalization of a Poisson branching process in which random time delays are permitted in the generation of events. Particular attention is given to the limit in which the number of branching stages is infinite while the average number of added events per event of the previous stage is infinitesimal. In the special case when the branching is instantaneous this limit of continuous branching corresponds to the well-known Yule--Furry process with an initial Poisson population. The Poisson branching point process provides a useful description for many problems in various scientific disciplines, such as the behavior of electron multipliers, neutron chain reactions, and cosmic ray showers

  14. The Lagrangian Points

    Science.gov (United States)

    Linton, J. Oliver

    2017-01-01

    There are five unique points in a star/planet system where a satellite can be placed whose orbital period is equal to that of the planet. Simple methods for calculating the positions of these points, or at least justifying their existence, are developed.

  15. Publication point indicators

    DEFF Research Database (Denmark)

    Elleby, Anita; Ingwersen, Peter

    2010-01-01

    ; the Cumulated Publication Point Indicator (CPPI), which graphically illustrates the cumulated gain of obtained vs. ideal points, both seen as vectors; and the normalized Cumulated Publication Point Index (nCPPI) that represents the cumulated gain of publication success as index values, either graphically......The paper presents comparative analyses of two publication point systems, The Norwegian and the in-house system from the interdisciplinary Danish Institute of International Studies (DIIS), used as case in the study for publications published 2006, and compares central citation-based indicators...... with novel publication point indicators (PPIs) that are formalized and exemplified. Two diachronic citation windows are applied: 2006-07 and 2006-08. Web of Science (WoS) as well as Google Scholar (GS) are applied to observe the cite delay and citedness for the different document types published by DIIS...

  16. Multispectral Image Feature Points

    Directory of Open Access Journals (Sweden)

    Cristhian Aguilera

    2012-09-01

    Full Text Available This paper presents a novel feature point descriptor for the multispectral image case: Far-Infrared and Visible Spectrum images. It allows matching interest points on images of the same scene but acquired in different spectral bands. Initially, points of interest are detected on both images through a SIFT-like based scale space representation. Then, these points are characterized using an Edge Oriented Histogram (EOH descriptor. Finally, points of interest from multispectral images are matched by finding nearest couples using the information from the descriptor. The provided experimental results and comparisons with similar methods show both the validity of the proposed approach as well as the improvements it offers with respect to the current state-of-the-art.

  17. Do acupuncture points exist?

    International Nuclear Information System (INIS)

    Yan Xiaohui; Zhang Xinyi; Liu Chenglin; Dang, Ruishan; Huang Yuying; He Wei; Ding Guanghong

    2009-01-01

    We used synchrotron x-ray fluorescence analysis to probe the distribution of four chemical elements in and around acupuncture points, two located in the forearm and two in the lower leg. Three of the four acupuncture points showed significantly elevated concentrations of elements Ca, Fe, Cu and Zn in relation to levels in the surrounding tissue, with similar elevation ratios for Cu and Fe. The mapped distribution of these elements implies that each acupuncture point seems to be elliptical with the long axis along the meridian. (note)

  18. Do acupuncture points exist?

    Energy Technology Data Exchange (ETDEWEB)

    Yan Xiaohui; Zhang Xinyi [Department of Physics, Surface Physics Laboratory (State Key Laboratory), and Synchrotron Radiation Research Center of Fudan University, Shanghai 200433 (China); Liu Chenglin [Physics Department of Yancheng Teachers' College, Yancheng 224002 (China); Dang, Ruishan [Second Military Medical University, Shanghai 200433 (China); Huang Yuying; He Wei [Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100039 (China); Ding Guanghong [Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)

    2009-05-07

    We used synchrotron x-ray fluorescence analysis to probe the distribution of four chemical elements in and around acupuncture points, two located in the forearm and two in the lower leg. Three of the four acupuncture points showed significantly elevated concentrations of elements Ca, Fe, Cu and Zn in relation to levels in the surrounding tissue, with similar elevation ratios for Cu and Fe. The mapped distribution of these elements implies that each acupuncture point seems to be elliptical with the long axis along the meridian. (note)

  19. Marine Point Forecasts

    Science.gov (United States)

    will link to the zone forecast and then allow further zooming to the point of interest whereas on the Honolulu, HI Chicago, IL Northern Indiana, IN Lake Charles, LA New Orleans, LA Boston, MA Caribou, ME

  20. Critical-point nuclei

    International Nuclear Information System (INIS)

    Clark, R.M.

    2004-01-01

    It has been suggested that a change of nuclear shape may be described in terms of a phase transition and that specific nuclei may lie close to the critical point of the transition. Analytical descriptions of such critical-point nuclei have been introduced recently and they are described briefly. The results of extensive searches for possible examples of critical-point behavior are presented. Alternative pictures, such as describing bands in the candidate nuclei using simple ΔK = 0 and ΔK = 2 rotational-coupling models, are discussed, and the limitations of the different approaches highlighted. A possible critical-point description of the transition from a vibrational to rotational pairing phase is suggested

  1. National Wetlands Inventory Points

    Data.gov (United States)

    Minnesota Department of Natural Resources — Wetland point features (typically wetlands that are too small to be as area features at the data scale) mapped as part of the National Wetlands Inventory (NWI). The...

  2. Allegheny County Address Points

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset contains address points which represent physical address locations assigned by the Allegheny County addressing authority. Data is updated by County...

  3. Iowa Geologic Sampling Points

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — Point locations of geologic samples/files in the IGS repository. Types of samples include well cuttings, outcrop samples, cores, drillers logs, measured sections,...

  4. Characterizing fixed points

    Directory of Open Access Journals (Sweden)

    Sanjo Zlobec

    2017-04-01

    Full Text Available A set of sufficient conditions which guarantee the existence of a point x⋆ such that f(x⋆ = x⋆ is called a "fixed point theorem". Many such theorems are named after well-known mathematicians and economists. Fixed point theorems are among most useful ones in applied mathematics, especially in economics and game theory. Particularly important theorem in these areas is Kakutani's fixed point theorem which ensures existence of fixed point for point-to-set mappings, e.g., [2, 3, 4]. John Nash developed and applied Kakutani's ideas to prove the existence of (what became known as "Nash equilibrium" for finite games with mixed strategies for any number of players. This work earned him a Nobel Prize in Economics that he shared with two mathematicians. Nash's life was dramatized in the movie "Beautiful Mind" in 2001. In this paper, we approach the system f(x = x differently. Instead of studying existence of its solutions our objective is to determine conditions which are both necessary and sufficient that an arbitrary point x⋆ is a fixed point, i.e., that it satisfies f(x⋆ = x⋆. The existence of solutions for continuous function f of the single variable is easy to establish using the Intermediate Value Theorem of Calculus. However, characterizing fixed points x⋆, i.e., providing answers to the question of finding both necessary and sufficient conditions for an arbitrary given x⋆ to satisfy f(x⋆ = x⋆, is not simple even for functions of the single variable. It is possible that constructive answers do not exist. Our objective is to find them. Our work may require some less familiar tools. One of these might be the "quadratic envelope characterization of zero-derivative point" recalled in the next section. The results are taken from the author's current research project "Studying the Essence of Fixed Points". They are believed to be original. The author has received several feedbacks on the preliminary report and on parts of the project

  5. Photoacoustic Point Source

    International Nuclear Information System (INIS)

    Calasso, Irio G.; Craig, Walter; Diebold, Gerald J.

    2001-01-01

    We investigate the photoacoustic effect generated by heat deposition at a point in space in an inviscid fluid. Delta-function and long Gaussian optical pulses are used as sources in the wave equation for the displacement potential to determine the fluid motion. The linear sound-generation mechanism gives bipolar photoacoustic waves, whereas the nonlinear mechanism produces asymmetric tripolar waves. The salient features of the photoacoustic point source are that rapid heat deposition and nonlinear thermal expansion dominate the production of ultrasound

  6. Unconventional Quantum Critical Points

    OpenAIRE

    Xu, Cenke

    2012-01-01

    In this paper we review the theory of unconventional quantum critical points that are beyond the Landau's paradigm. Three types of unconventional quantum critical points will be discussed: (1). The transition between topological order and semiclassical spin ordered phase; (2). The transition between topological order and valence bond solid phase; (3). The direct second order transition between different competing orders. We focus on the field theory and universality class of these unconventio...

  7. SharePoint governance

    OpenAIRE

    Ali, Mudassar

    2013-01-01

    Masteroppgave i informasjons- og kommunikasjonsteknologi IKT590 2013 – Universitetet i Agder, Grimstad SharePoint is a web-based business collaboration platform from Microsoft which is very robust and dynamic in nature. The platform has been in the market for more than a decade and has been adapted by large number of organisations in the world. The platform has become larger in scale, richer in features and is improving consistently with every new version. However, SharePoint ...

  8. Publication point indicators

    DEFF Research Database (Denmark)

    Elleby, Anita; Ingwersen, Peter

    2010-01-01

    The paper presents comparative analyses of two publication point systems, The Norwegian and the in-house system from the interdiscplinary Danish Institute for International Studies (DIIS), used as case in the study for publications published 2006, and compares central citation-based indicators...... with novel publication point indicators (PPIs) that are formalized and exemplified. Two diachronic citation windows are applied: 2006-07 and 2006-08. Web of Science (WoS) as well as Google Scholar (GS) are applied to observe the cite delay and citedness for the different document types published by DIIS...... for all document types. Statistical significant correlations were only found between WoS and GS and the two publication point systems in between, respectively. The study demonstrates how the nCPPI can be applied to institutions as evaluation tools supplementary to JCI in various combinations...

  9. New Novae snack point

    CERN Document Server

    2012-01-01

    Located next to the car park by the flag poles, a few metres from the Main CERN Reception (building 33), a new snack point catered by Novae will open to the public on Wednesday 8 August. More information will be available in the next issue of the Bulletin!

  10. [Clinical key points. Gonioscopy].

    Science.gov (United States)

    Hamard, P

    2007-05-01

    Gonioscopy should be performed in all patients with glaucoma or suspected of having glaucoma. Four points are systematically evaluated: the width of the angle, the degree of trabecular pigmentation, the iridotrabecular appositions or synechia, and the level of iris insertion and the shape of the peripheral iris profile.

  11. ACS Zero Point Verification

    Science.gov (United States)

    Dolphin, Andrew

    2005-07-01

    The uncertainties in the photometric zero points create a fundamental limit to the accuracy of photometry. The current state of the ACS calibration is surprisingly poor, with zero point uncertainties of 0.03 magnitudes. The reason for this is that the ACS calibrations are based primarily on semi-emprical synthetic zero points and observations of fields too crowded for accurate ground-based photometry. I propose to remedy this problem by obtaining ACS images of the omega Cen standard field with all nine broadband ACS/WFC filters. This will permit the direct determination of the ACS zero points by comparison with excellent ground-based photometry, and should reduce their uncertainties to less than 0.01 magnitudes. A second benefit is that it will facilitate the comparison of the WFPC2 and ACS photometric systems, which will be important as WFPC2 is phased out and ACS becomes HST's primary imager. Finally, three of the filters will be repeated from my Cycle 12 observations, allowing for a measurement of any change in sensitivity.

  12. Point Lepreau generating station

    International Nuclear Information System (INIS)

    Ganong, G.H.D.; Strang, A.E.; Gunter, G.E.; Thompson, T.S.

    Point Lepreau-1 reactor is a 600 MWe generating station expected to be in service by October 1979. New Brunswick is suffering a 'catch up' phenomenon in load growth and needs to decrease dependence on foreign oil. The site is on salt water and extensive study has gone into corrosion control. Project management, financing and scheduling have unique aspects. (E.C.B.)

  13. Least fixed points revisited

    NARCIS (Netherlands)

    J.W. de Bakker (Jaco)

    1975-01-01

    textabstractParameter mechanisms for recursive procedures are investigated. Contrary to the view of Manna et al., it is argued that both call-by-value and call-by-name mechanisms yield the least fixed points of the functionals determined by the bodies of the procedures concerned. These functionals

  14. Point kinetics modeling

    International Nuclear Information System (INIS)

    Kimpland, R.H.

    1996-01-01

    A normalized form of the point kinetics equations, a prompt jump approximation, and the Nordheim-Fuchs model are used to model nuclear systems. Reactivity feedback mechanisms considered include volumetric expansion, thermal neutron temperature effect, Doppler effect and void formation. A sample problem of an excursion occurring in a plutonium solution accidentally formed in a glovebox is presented

  15. Melting point of yttria

    International Nuclear Information System (INIS)

    Skaggs, S.R.

    1977-06-01

    Fourteen samples of 99.999 percent Y 2 O 3 were melted near the focus of a 250-W CO 2 laser. The average value of the observed melting point along the solid-liquid interface was 2462 +- 19 0 C. Several of these same samples were then melted in ultrahigh-purity oxygen, nitrogen, helium, or argon and in water vapor. No change in the observed temperature was detected, with the exception of a 20 0 C increase in temperature from air to helium gas. Post test examination of the sample characteristics, clarity, sphericity, and density is presented, along with composition. It is suggested that yttria is superior to alumina as a secondary melting-point standard

  16. 'Saddle-point' ionization

    International Nuclear Information System (INIS)

    Gay, T.J.; Hale, E.B.; Irby, V.D.; Olson, R.E.; Missouri Univ., Rolla; Berry, H.G.

    1988-01-01

    We have studied the ionization of rare gases by protons at intermediate energies, i.e., energies at which the velocities of the proton and the target-gas valence electrons are comparable. A significant channel for electron production in the forward direction is shown to be 'saddle-point' ionization, in which electrons are stranded on or near the saddle-point of electric potential between the receding projectile and the ionized target. Such electrons yield characteristic energy spectra, and contribute significantly to forward-electron-production cross sections. Classical trajectory Monte Carlo calculations are found to provide qualitative agreement with our measurements and the earlier measurements of Rudd and coworkers, and reproduce, in detail, the features of the general ionization spectra. (orig.)

  17. High boiling point hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Pier, M

    1929-04-29

    A process is given for the production of hydrocarbons of high boiling point, such as lubricating oils, from bituminous substances, such as varieties of coal, shale, or other solid distillable carbonaceous materials. The process consists of treating the initial materials with organic solvents and then subjecting the products extracted from the initial materials, preferably directly, to a reducing treatment in respect to temperature, pressure, and time. The reduction treatment is performed by means of hydrogen under pressure.

  18. Critical point predication device

    International Nuclear Information System (INIS)

    Matsumura, Kazuhiko; Kariyama, Koji.

    1996-01-01

    An operation for predicting a critical point by using a existent reverse multiplication method has been complicated, and an effective multiplication factor could not be plotted directly to degrade the accuracy for the prediction. The present invention comprises a detector counting memory section for memorizing the counting sent from a power detector which monitors the reactor power, a reverse multiplication factor calculation section for calculating the reverse multiplication factor based on initial countings and current countings of the power detector, and a critical point prediction section for predicting the criticality by the reverse multiplication method relative to effective multiplication factors corresponding to the state of the reactor core previously determined depending on the cases. In addition, a reactor core characteristic calculation section is added for analyzing an effective multiplication factor depending on the state of the reactor core. Then, if the margin up to the criticality is reduced to lower than a predetermined value during critical operation, an alarm is generated to stop the critical operation when generation of a period of more than a predetermined value predicted by succeeding critical operation. With such procedures, forecasting for the critical point can be easily predicted upon critical operation to greatly mitigate an operator's burden and improve handling for the operation. (N.H.)

  19. At the Tipping Point

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H. S.

    2011-02-28

    There comes a time in every field of science when things suddenly change. While it might not be immediately apparent that things are different, a tipping point has occurred. Biology is now at such a point. The reason is the introduction of high-throughput genomics-based technologies. I am not talking about the consequences of the sequencing of the human genome (and every other genome within reach). The change is due to new technologies that generate an enormous amount of data about the molecular composition of cells. These include proteomics, transcriptional profiling by sequencing, and the ability to globally measure microRNAs and post-translational modifications of proteins. These mountains of digital data can be mapped to a common frame of reference: the organism’s genome. With the new high-throughput technologies, we can generate tens of thousands of data points from each sample. Data are now measured in terabytes and the time necessary to analyze data can now require years. Obviously, we can’t wait to interpret the data fully before the next experiment. In fact, we might never be able to even look at all of it, much less understand it. This volume of data requires sophisticated computational and statistical methods for its analysis and is forcing biologists to approach data interpretation as a collaborative venture.

  20. Maximum power point tracking

    International Nuclear Information System (INIS)

    Enslin, J.H.R.

    1990-01-01

    A well engineered renewable remote energy system, utilizing the principal of Maximum Power Point Tracking can be m ore cost effective, has a higher reliability and can improve the quality of life in remote areas. This paper reports that a high-efficient power electronic converter, for converting the output voltage of a solar panel, or wind generator, to the required DC battery bus voltage has been realized. The converter is controlled to track the maximum power point of the input source under varying input and output parameters. Maximum power point tracking for relative small systems is achieved by maximization of the output current in a battery charging regulator, using an optimized hill-climbing, inexpensive microprocessor based algorithm. Through practical field measurements it is shown that a minimum input source saving of 15% on 3-5 kWh/day systems can easily be achieved. A total cost saving of at least 10-15% on the capital cost of these systems are achievable for relative small rating Remote Area Power Supply systems. The advantages at larger temperature variations and larger power rated systems are much higher. Other advantages include optimal sizing and system monitor and control

  1. A hypomorphic Cbx3 allele causes prenatal growth restriction and ...

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... protein cannot be compensated by CBX3 and CBX5 proteins. (Aucott et al. ..... contained no milk (C.f. figure 4a with 4d) and most were found dead or dying ..... tissues of mice protects against high fat diet-induced obesity and.

  2. Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome.

    Science.gov (United States)

    McLarren, Keith W; Severson, Tesa M; du Souich, Christèle; Stockton, David W; Kratz, Lisa E; Cunningham, David; Hendson, Glenda; Morin, Ryan D; Wu, Diane; Paul, Jessica E; An, Jianghong; Nelson, Tanya N; Chou, Athena; DeBarber, Andrea E; Merkens, Louise S; Michaud, Jacques L; Waters, Paula J; Yin, Jingyi; McGillivray, Barbara; Demos, Michelle; Rouleau, Guy A; Grzeschik, Karl-Heinz; Smith, Raffaella; Tarpey, Patrick S; Shears, Debbie; Schwartz, Charles E; Gecz, Jozef; Stratton, Michael R; Arbour, Laura; Hurlburt, Jane; Van Allen, Margot I; Herman, Gail E; Zhao, Yongjun; Moore, Richard; Kelley, Richard I; Jones, Steven J M; Steiner, Robert D; Raymond, F Lucy; Marra, Marco A; Boerkoel, Cornelius F

    2010-12-10

    CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del [p.Lys232del]) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (NSDHL), a gene that encodes an enzyme in the cholesterol biosynthesis pathway. We also found that males with intellectual disability in another reported family with an NSDHL mutation (c.1098 dup [p.Arg367SerfsX33]) have CKS. These two mutations, which alter protein folding, show temperature-sensitive protein stability and complementation in Erg26-deficient yeast. As described for the allelic disorder CHILD syndrome, cells and cerebrospinal fluid from CKS patients have increased methyl sterol levels. We hypothesize that methyl sterol accumulation, not only cholesterol deficiency, causes CKS, given that cerebrospinal fluid cholesterol, plasma cholesterol, and plasma 24S-hydroxycholesterol levels are normal in males with CKS. In summary, CKS expands the spectrum of cholesterol-related disorders and insight into the role of cholesterol in human development. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Hypomorphic Temperature-Sensitive Alleles of NSDHL Cause CK Syndrome

    OpenAIRE

    McLarren, Keith W.; Severson, Tesa M.; du Souich, Christèle; Stockton, David W.; Kratz, Lisa E.; Cunningham, David; Hendson, Glenda; Morin, Ryan D.; Wu, Diane; Paul, Jessica E.; An, Jianghong; Nelson, Tanya N.; Chou, Athena; DeBarber, Andrea E.; Merkens, Louise S.

    2010-01-01

    CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del [p.Lys232del]) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (NSDHL), a gene that encodes an enzyme in the cholestero...

  4. Vernal Point and Anthropocene

    Science.gov (United States)

    Chavez-Campos, Teodosio; Chavez S, Nadia; Chavez-Sumarriva, Israel

    2014-05-01

    The time scale was based on the internationally recognized formal chronostratigraphical /geochronological subdivisions of time: The Phanerozoic Eonathem/Eon; the Cenozoic Erathem/Era; the Quaternary System/Period; the Pleistocene and Holocene Series/Epoch. The Quaternary was divided into: (1) The Pleistocene that was characterized by cycles of glaciations (intervals between 40,000 and 100,000 years). (2) The Holocene that was an interglacial period that began about 12,000 years ago. It was believed that the Milankovitch cycles (eccentricity, axial tilt and the precession of the equinoxes) were responsible for the glacial and interglacial Holocene periods. The magnetostratigraphic units have been widely used for global correlations valid for Quaternary. The gravitational influence of the sun and moon on the equatorial bulges of the mantle of the rotating earth causes the precession of the earth. The retrograde motion of the vernal point through the zodiacal band is 26,000 years. The Vernal point passes through each constellation in an average of 2000 years and this period of time was correlated to Bond events that were North Atlantic climate fluctuations occurring every ≡1,470 ± 500 years throughout the Holocene. The vernal point retrogrades one precessional degree approximately in 72 years (Gleissberg-cycle) and approximately enters into the Aquarius constellation on March 20, 1940. On earth this entry was verify through: a) stability of the magnetic equator in the south central zone of Peru and in the north zone of Bolivia, b) the greater intensity of equatorial electrojet (EEJ) in Peru and Bolivia since 1940. With the completion of the Holocene and the beginning of the Anthropocene (widely popularized by Paul Crutzen) it was proposed the date of March 20, 1940 as the beginning of the Anthropocene. The date proposed was correlated to the work presented in IUGG (Italy 2007) with the title "Cusco base meridian for the study of geophysical data"; Cusco was

  5. Point/Counterpoint

    DEFF Research Database (Denmark)

    Ungar, David; Ernst, Erik

    2007-01-01

    Point Argument: "Dynamic Languages (in Reactive Environments) Unleash Creativity," by David Ungar. For the sake of creativity, the profession needs to concentrate more on inventing new and better dynamic languages and environments and less on improving static languages. Counterpoint Argument......: "Explicitly Declared Static Types: The Missing Links," by Erik Ernst. How do we understand software? Using it is a powerful approach, but it provides examples of properties, not general truths. Some static knowledge is needed. This department is part of a special issue on dynamically typed languages....

  6. Mise au point

    African Journals Online (AJOL)

    tomie est replacé et fixé par des fils d'acier, krönlein lais- sait ce fragment pédiculé au fascia temporalis afin d'évi- ter la dépression de la fosse temporale due à la désinser- tion du muscle temporal [20] ; dans notre série, après reconstitution du cadre, le muscle temporal est suturé à son point d'insertion. pour les tumeurs ...

  7. Torsades de Pointes

    Directory of Open Access Journals (Sweden)

    Richard J Chen, MD

    2018-04-01

    Full Text Available History of present illness: 70-year-old male with a history ventricular arrhythmia, AICD (automated implantable cardioverter defibrillator, coronary artery disease and cardiac stents presented to the Emergency Department after three AICD discharges with dyspnea but no chest pain. During triage, he was found to have an irregular radial pulse and was placed on a cardiac monitor. Significant findings: The patient was found to be in a polymorphic ventricular tachycardia; he was alert, awake and asymptomatic. A rhythm strip showed a wide complex tachycardia with the QRS complex varying in amplitude around the isoelectric line consistent with Torsades de Pointes. Discussion: Torsades de Pointes (TdP is a specific type of polymorphic ventricular tachycardia. The arrhythmia’s characteristic morphology consists of the QRS complex “twisting” around the isoelectric line with gradual variation of the amplitude, reflecting its literal translation of “twisting of the points.”1 This arrhythmia occurs in the context of prolonged QT. The most common form of acquired QT prolongation is medication induced. Common causes include antiarrhythmics, antipsychotics, antiemetics, and antibiotics.2 Patient specific risk factors include female sex, bradycardia, hypokalemia, hypomagnesemia, hypocalcemia, hypothermia and heart disease.3 In the setting of prolonged QT, the repolarization phase is extended. TdP is initiated when a PVC (premature ventricular contraction occurs during this repolarization, known as an ‘R on T’ phenomenon. TdP is often asymptomatic and self-limited. The danger in TdP is its potential to deteriorate into ventricular fibrillation. A mainstay of management of TdP is prevention of risk factors when possible.4 Unstable patients should be treated with synchronized cardioversion. Magnesium sulfate should be administered in all cases of TdP.1 If a patient is not responsive to magnesium, consider isoproterenol, amiodarone, and overdrive

  8. Pointing control for LDR

    Science.gov (United States)

    Yam, Y.; Briggs, C.

    1988-01-01

    One important aspect of the LDR control problem is the possible excitations of structural modes due to random disturbances, mirror chopping, and slewing maneuvers. An analysis was performed to yield a first order estimate of the effects of such dynamic excitations. The analysis involved a study of slewing jitters, chopping jitters, disturbance responses, and pointing errors, making use of a simplified planar LDR model which describes the LDR dynamics on a plane perpendicular to the primary reflector. Briefly, the results indicate that the command slewing profile plays an important role in minimizing the resultant jitter, even to a level acceptable without any control action. An optimal profile should therefore be studied.

  9. Point of Care Ultrasound

    DEFF Research Database (Denmark)

    Dietrich, Christoph F; Goudie, Adrian; Chiorean, Liliana

    2017-01-01

    Over the last decade, the use of portable ultrasound scanners has enhanced the concept of point of care ultrasound (PoC-US), namely, "ultrasound performed at the bedside and interpreted directly by the treating clinician." PoC-US is not a replacement for comprehensive ultrasound, but rather allows...... and critical care medicine, cardiology, anesthesiology, rheumatology, obstetrics, neonatology, gynecology, gastroenterology and many other applications. In the future, PoC-US will be more diverse than ever and be included in medical student training....

  10. The point on.

    International Nuclear Information System (INIS)

    1996-01-01

    In this last article, we find the point of view about the world petroleum activity, the reserves and the recent discoveries, the deep offshore, the technological developments in petroleum upstream. The petroleum situation in China is treated. The trends of world refining are described. The recent technological developments in the petroleum downstream are detailed. The prices of crude oil and the refining margins are the subject of a chapter. The investments of hydrocarbons area are given, the world trade and the lng projects, the gas availability in Western Europe have their place. The trends of European automobile industry and the fuels distribution are also discussed. (N.C.)

  11. Relative Critical Points

    Directory of Open Access Journals (Sweden)

    Debra Lewis

    2013-05-01

    Full Text Available Relative equilibria of Lagrangian and Hamiltonian systems with symmetry are critical points of appropriate scalar functions parametrized by the Lie algebra (or its dual of the symmetry group. Setting aside the structures – symplectic, Poisson, or variational – generating dynamical systems from such functions highlights the common features of their construction and analysis, and supports the construction of analogous functions in non-Hamiltonian settings. If the symmetry group is nonabelian, the functions are invariant only with respect to the isotropy subgroup of the given parameter value. Replacing the parametrized family of functions with a single function on the product manifold and extending the action using the (coadjoint action on the algebra or its dual yields a fully invariant function. An invariant map can be used to reverse the usual perspective: rather than selecting a parametrized family of functions and finding their critical points, conditions under which functions will be critical on specific orbits, typically distinguished by isotropy class, can be derived. This strategy is illustrated using several well-known mechanical systems – the Lagrange top, the double spherical pendulum, the free rigid body, and the Riemann ellipsoids – and generalizations of these systems.

  12. Reassessing Function Points

    Directory of Open Access Journals (Sweden)

    G.R. Finnie

    1997-05-01

    Full Text Available Accurate estimation of the size and development effort for software projects requires estimation models which can be used early enough in the development life cycle to be of practical value. Function Point Analysis (FPA has become possibly the most widely used estimation technique in practice. However the technique was developed in the data processing environment of the 1970's and, despite undergoing considerable reassessment and formalisation, still attracts criticism for the weighting scoring it employs and for the way in which the function point score is adapted for specific system characteristics. This paper reviews the validity of the weighting scheme and the value of adjusting for system characteristics by studying their effect in a sample of 299 software developments. In general the value adjustment scheme does not appear to cater for differences in productivity. The weighting scheme used to adjust system components in terms of being simple, average or complex also appears suspect and should be redesigned to provide a more realistic estimate of system functionality.

  13. Bright point study

    International Nuclear Information System (INIS)

    Tang, F.; Harvey, K.; Bruner, M.; Kent, B.; Antonucci, E.

    1982-01-01

    Transition region and coronal observations of bright points by instruments aboard the Solar Maximum Mission and high resolution photospheric magnetograph observations on September 11, 1980 are presented. A total of 31 bipolar ephemeral regions were found in the photosphere from birth in 9.3 hours of combined magnetograph observations from three observatories. Two of the three ephemeral regions present in the field of view of the Ultraviolet Spectrometer-Polarimeter were observed in the C IV 1548 line. The unobserved ephemeral region was determined to be the shortest-lived (2.5 hr) and lowest in magnetic flux density (13G) of the three regions. The Flat Crystal Spectrometer observed only low level signals in the O VIII 18.969 A line, which were not statistically significant to be positively identified with any of the 16 ephemeral regions detected in the photosphere. In addition, the data indicate that at any given time there lacked a one-to-one correspondence between observable bright points and photospheric ephemeral regions, while more ephemeral regions were observed than their counterparts in the transition region and the corona

  14. Referential Zero Point

    Directory of Open Access Journals (Sweden)

    Matjaž Potrč

    2016-04-01

    Full Text Available Perhaps the most important controversy in which ordinary language philosophy was involved is that of definite descriptions, presenting referential act as a community-involving communication-intention endeavor, thereby opposing the direct acquaintance-based and logical proper names inspired reference aimed at securing truth conditions of referential expression. The problem of reference is that of obtaining access to the matters in the world. This access may be forthcoming through the senses, or through descriptions. A review of how the problem of reference is handled shows though that one main practice is to indulge in relations of acquaintance supporting logical proper names, demonstratives, indexicals and causal or historical chains. This testifies that the problem of reference involves the zero point, and with it phenomenology of intentionality. Communication-intention is but one dimension of rich phenomenology that constitutes an agent’s experiential space, his experiential world. Zero point is another constitutive aspect of phenomenology involved in the referential relation. Realizing that the problem of reference is phenomenology based opens a new perspective upon the contribution of analytical philosophy in this area, reconciling it with continental approach, and demonstrating variations of the impossibility related to the real. Chromatic illumination from the cognitive background empowers the referential act, in the best tradition of ordinary language philosophy.

  15. Point Pollution Sources Dimensioning

    Directory of Open Access Journals (Sweden)

    Georgeta CUCULEANU

    2011-06-01

    Full Text Available In this paper a method for determining the main physical characteristics of the point pollution sources is presented. It can be used to find the main physical characteristics of them. The main physical characteristics of these sources are top inside source diameter and physical height. The top inside source diameter is calculated from gas flow-rate. For reckoning the physical height of the source one takes into account the relation given by the proportionality factor, defined as ratio between the plume rise and physical height of the source. The plume rise depends on the gas exit velocity and gas temperature. That relation is necessary for diminishing the environmental pollution when the production capacity of the plant varies, in comparison with the nominal one.

  16. Critical Points of Contact

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Wind, Simon; Lanng, Ditte Bendix

    2012-01-01

    In this brief article, we shall illustrate the application of the analytical and interventionist concept of ‘Critical Points of Contact’ (CPC) through a number of urban design studios. The notion of CPC has been developed over a span of the last three to four years and is reported in more detail...... elsewhere (Jensen & Morelli 2011). In this article, we will only discuss the conceptual and theoretical framing superficially, since our real interest is to show and discuss the concept's application value to spatial design in a number of urban design studios. The 'data' or the projects presented are seven...... in urban design at Aalborg University, where urban design consists of both an analytical and an interventionist field of operation. Furthermore, the content of the CPC concept links to research in mobilities, the network city, and urban design. These are among the core pillars of both the masters programme...

  17. Point defects in platinum

    International Nuclear Information System (INIS)

    Piercy, G.R.

    1960-01-01

    An investigation was made of the mobility and types of point defect introduced in platinum by deformation in liquid nitrogen, quenching into water from 1600 o C, or reactor irradiation at 50 o C. In all cases the activation energy for motion of the defect was determined from measurements of electrical resistivity. Measurements of density, hardness, and x-ray line broadening were also made there applicable. These experiments indicated that the principal defects remaining in platinum after irradiation were single vacant lattice sites and after quenching were pairs of vacant lattice sites. Those present after deformation In liquid nitrogen were single vacant lattice sites and another type of defect, perhaps interstitial atoms. (author)

  18. Virtual turning points

    CERN Document Server

    Honda, Naofumi; Takei, Yoshitsugu

    2015-01-01

    The discovery of a virtual turning point truly is a breakthrough in WKB analysis of higher order differential equations. This monograph expounds the core part of its theory together with its application to the analysis of higher order Painlevé equations of the Noumi–Yamada type and to the analysis of non-adiabatic transition probability problems in three levels. As M.V. Fedoryuk once lamented, global asymptotic analysis of higher order differential equations had been thought to be impossible to construct. In 1982, however, H.L. Berk, W.M. Nevins, and K.V. Roberts published a remarkable paper in the Journal of Mathematical Physics indicating that the traditional Stokes geometry cannot globally describe the Stokes phenomena of solutions of higher order equations; a new Stokes curve is necessary.

  19. The Temporal Tipping Point

    DEFF Research Database (Denmark)

    Hermann, A. K.

    2016-01-01

    “Slow journalism” is a term anthropologist and sociologists sometimes use to describe their empirical work, ethnography. To journalists and media observers, meanwhile, “slow journalism” signifies a newfound dedication to serious long-form journalism. Not surprisingly, thus, “ethnographic journalism......”—a genre where reporters adopt research strategies from social science—takes “slow” to the extreme. Immersing themselves in communities for weeks, months and years, ethnographic journalists seek to gain what anthropologists call “the native's point of view”. Based on in-depth interviews with practitioners...... and analyses of their journalistic works, this paper offers a study of ethnographic journalism suggesting that slow time operates in at least three separate registers. First, in terms of regimentation, ethnographic journalism is mostly long-form pieces that demand time-consuming research and careful writing...

  20. The Point Mass Concept

    Directory of Open Access Journals (Sweden)

    Lehnert B.

    2011-04-01

    Full Text Available A point-mass concept has been elaborated from the equations of the gravitational field. One application of these deductions results in a black hole configuration of the Schwarzschild type, having no electric charge and no angular momentum. The critical mass of a gravitational collapse with respect to the nuclear binding energy is found to be in the range of 0.4 to 90 solar masses. A second application is connected with the spec- ulation about an extended symmetric law of gravitation, based on the options of positive and negative mass for a particle at given positive energy. This would make masses of equal polarity attract each other, while masses of opposite polarity repel each other. Matter and antimatter are further proposed to be associated with the states of positive and negative mass. Under fully symmetric conditions this could provide a mechanism for the separation of antimatter from matter at an early stage of the universe.

  1. The Point Mass Concept

    Directory of Open Access Journals (Sweden)

    Lehnert B.

    2011-04-01

    Full Text Available A point-mass concept has been elaborated from the equations of the gravitational field. One application of these deductions results in a black hole configuration of the Schwarzschild type, having no electric charge and no angular momentum. The critical mass of a gravitational collapse with respect to the nuclear binding energy is found to be in the range of 0.4 to 90 solar masses. A second application is connected with the speculation about an extended symmetric law of gravitation, based on the options of positive and negative mass for a particle at given positive energy. This would make masses of equal polarity attract each other, while masses of opposite polarity repel each other. Matter and antimatter are further proposed to be associated with the states of positive and negative mass. Under fully symmetric conditions this could provide a mechanism for the separation of antimatter from matter at an early stage of the universe.

  2. May 2002 Lidar Point Data of Southern California Coastline: Dana Point to Point La Jolla

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains lidar point data from a strip of Southern California coastline (including water, beach, cliffs, and top of cliffs) from Dana Point to Point La...

  3. September 2002 Lidar Point Data of Southern California Coastline: Dana Point to Point La Jolla

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains lidar point data from a strip of Southern California coastline (including water, beach, cliffs, and top of cliffs) from Dana Point to Point La...

  4. Learning power point 2000 easily

    Energy Technology Data Exchange (ETDEWEB)

    Mon, In Su; Je, Jung Suk

    2000-05-15

    This book introduces power point 2000, which gives descriptions what power point is, what we can do with power point 2000, is it possible to install power point 2000 in my computer? Let's run power point, basic of power point such as new presentation, writing letter, using text box, changing font size, color and shape, catching power user, insertion of word art and creating of new file. It also deals with figure, chart, graph, making multimedia file, presentation, know-how of power point for teachers and company workers.

  5. ATLAS Point 1 Construction

    CERN Multimedia

    Inigo-Golfin, J

    After 3 years of work in point 1, a number of surface buildings have already been completed and handed over to CERN (the control, the gas and the cooling and ventilation buildings) and, probably more appealing to the public, 60,000 m3 of earth have already been excavated from underground. At present, the technical cavern USA15 and its access shaft are almost finished, leaving only the main cavern and the liaison galleries to be completed in the coming year and a half. The main cavern has been excavated down to the radiation limit and its walls and vault will presently be concreted (see below the picture of the section of the vault with the impressive shell of 1.2 m thickness). The excavation of the bench (27 vertical metres to go yet!) will proceed from August, when some additional civil engineering work in the LHC tunnel will be undertaken. Needless to say many different services are necessary around the detector, both for its installation and future operation for physics. To that end much of the heavy...

  6. Point 1 Updates

    CERN Multimedia

    Inigo-Golfin, J.

    The ATLAS experimental area is located in Point 1, just across the main CERN entrance, in the commune of Meyrin. There people are ever so busy to finish the different infrastructures for ATLAS. Not only has Civil Engineering finished the construction of the USA15 technical cavern, but the excavation of the main UX15 cavern has resumed below the machine tunnel, after a brief halt to allow the construction of the UJ-caverns for the power converters of the LHC machine. The excavation work should end in August 2002. The UX15 hand-over to ATLAS is expected in April 2003. On the surface civil engineering is starting to complete the last two surface buildings (SDX1 and SH1), once the services (cooling pipes, ventilation ducts and the largest item, the lift modules and its lift of course) in the shaft PX15 have been completed. But the civil engineering is not all. A lot more is under way. The site installation of the steel structures in the caverns is to begin in Autumn, along with all the cooling pipes, airconditi...

  7. Rational points on varieties

    CERN Document Server

    Poonen, Bjorn

    2017-01-01

    This book is motivated by the problem of determining the set of rational points on a variety, but its true goal is to equip readers with a broad range of tools essential for current research in algebraic geometry and number theory. The book is unconventional in that it provides concise accounts of many topics instead of a comprehensive account of just one-this is intentionally designed to bring readers up to speed rapidly. Among the topics included are Brauer groups, faithfully flat descent, algebraic groups, torsors, étale and fppf cohomology, the Weil conjectures, and the Brauer-Manin and descent obstructions. A final chapter applies all these to study the arithmetic of surfaces. The down-to-earth explanations and the over 100 exercises make the book suitable for use as a graduate-level textbook, but even experts will appreciate having a single source covering many aspects of geometry over an unrestricted ground field and containing some material that cannot be found elsewhere. The origins of arithmetic (o...

  8. "Point de suspension"

    CERN Multimedia

    2004-01-01

    CERN - Globe of Science and Innovation 20 and 21 October Acrobatics, mime, a cappella singing, projections of images, a magical setting... a host of different tools of a grandeur matching that of the Universe they relate. A camera makes a massive zoom out to reveal the multiple dimensions of Nature. Freeze the frame: half way between the infinitesimally small and the infinitesimally large, a man suspends his everyday life (hence the title "Point de Suspension", which refers to the three dots at the end of an uncompleted sentence) to take a glimpse of the place he occupies in the great history of the Universe. An unusual perspective on what it means to be a human being... This wondrous show in the Globe of Science and Innovation, specially created by the Miméscope* company for the official ceremony marking CERN's fiftieth anniversary, is a gift from the Government of the Republic and Canton of Geneva, which also wishes to share this moment of wonder with the local population. There will be three perfo...

  9. "Point de suspension"

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ CERN - Globe of Science and Innovation 20 and 21 October Acrobatics, mime, a cappella singing, projections of images, a magical setting... a host of different tools of a grandeur matching that of the Universe they relate. A camera makes a massive zoom out to reveal the multiple dimensions of Nature. Freeze the frame: half way between the infinitesimally small and the infinitesimally large, a man suspends his everyday life (hence the title "Point de Suspension", which refers to the three dots at the end of an uncompleted sentence) to take a glimpse of the place he occupies in the great history of the Universe. An unusual perspective on what it means to be a human being... This wondrous show in the Globe of Science and Innovation, specially created by the Miméscope* company for the official ceremony marking CERN's fiftieth anniversary, is a gift from the Government of the Republic and Canton of Geneva, which also wishes to share this moment of wonder with the local pop...

  10. "Point de suspension"

    CERN Multimedia

    2004-01-01

    CERN - Globe of Science and Innovation 20 and 21 October Acrobatics, mime, a cappella singing, projections of images, a magical setting... a host of different tools of a grandeur matching that of the Universe they relate. A camera makes a massive zoom out to reveal the multiple dimensions of Nature. Freeze the frame: half way between the infinitesimally small and the infinitesimally large, a man suspends his everyday life (hence the title "Point de Suspension", which refers to the three dots at the end of an uncompleted sentence) to take a glimpse of the place he occupies in the great history of the Universe. An unusual perspective on what it means to be a human being... This spectacle in the Globe of Science and Innovation, specially created by the Miméscope* company for the official ceremony marking CERN's fiftieth anniversary, is a gift from the Government of the Republic and Canton of Geneva, which also wishes to share this moment of wonder with the local population. There will be three performances for...

  11. Solving discrete zero point problems

    NARCIS (Netherlands)

    van der Laan, G.; Talman, A.J.J.; Yang, Z.F.

    2004-01-01

    In this paper an algorithm is proposed to .nd a discrete zero point of a function on the collection of integral points in the n-dimensional Euclidean space IRn.Starting with a given integral point, the algorithm generates a .nite sequence of adjacent integral simplices of varying dimension and

  12. The Relationship between "MECP2" Mutation Type and Health Status and Service Use Trajectories over Time in a Rett Syndrome Population

    Science.gov (United States)

    Young, Deidra; Bebbington, Ami; de Klerk, Nick; Bower, Carol; Nagarajan, Lakshmi; Leonard, Helen

    2011-01-01

    This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over 6 years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use…

  13. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome

    DEFF Research Database (Denmark)

    Schönewolf-Greulich, Bitten; Tejada, Maria-Isabel; Stephens, K

    2016-01-01

    . Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X......-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism...

  14. The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens

    OpenAIRE

    Lewis, Candace R.; Staudinger, Kelsey; Scheck, Lena; Olive, M. Foster

    2013-01-01

    The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH) causes great harm to both the individual user and to society; yet, no studies have examined the effects...

  15. PowerPoint 2010 Bible

    CERN Document Server

    Wempen, Faithe

    2010-01-01

    Master PowerPoint and improve your presentation skills-with one book!. It's no longer enough to have slide after slide of text, bullets, and charts. It's not even enough to have good speaking skills if your PowerPoint slides bore your audience. Get the very most out of all that PowerPoint 2010 has to offer while also learning priceless tips and techniques for making good presentations in this new PowerPoint 2010 Bible. Well-known PowerPoint expert and author Faithe Wempen provides formatting tips; shows you how to work with drawings, tables, and SmartArt; introduces new collaboration tools; wa

  16. Imaging study on acupuncture points

    Science.gov (United States)

    Yan, X. H.; Zhang, X. Y.; Liu, C. L.; Dang, R. S.; Ando, M.; Sugiyama, H.; Chen, H. S.; Ding, G. H.

    2009-09-01

    The topographic structures of acupuncture points were investigated by using the synchrotron radiation based Dark Field Image (DFI) method. Four following acupuncture points were studied: Sanyinjiao, Neiguan, Zusanli and Tianshu. We have found that at acupuncture point regions there exists the accumulation of micro-vessels. The images taken in the surrounding tissue out of the acupuncture points do not show such kind of structure. It is the first time to reveal directly the specific structure of acupuncture points by X-ray imaging.

  17. Imaging study on acupuncture points

    International Nuclear Information System (INIS)

    Yan, X H; Zhang, X Y; Liu, C L; Dang, R S; Ando, M; Sugiyama, H; Chen, H S; Ding, G H

    2009-01-01

    The topographic structures of acupuncture points were investigated by using the synchrotron radiation based Dark Field Image (DFI) method. Four following acupuncture points were studied: Sanyinjiao, Neiguan, Zusanli and Tianshu. We have found that at acupuncture point regions there exists the accumulation of micro-vessels. The images taken in the surrounding tissue out of the acupuncture points do not show such kind of structure. It is the first time to reveal directly the specific structure of acupuncture points by X-ray imaging.

  18. Magic Pointing for Eyewear Computers

    DEFF Research Database (Denmark)

    Jalaliniya, Shahram; Mardanbegi, Diako; Pederson, Thomas

    2015-01-01

    In this paper, we propose a combination of head and eye movements for touchlessly controlling the "mouse pointer" on eyewear devices, exploiting the speed of eye pointing and accuracy of head pointing. The method is a wearable computer-targeted variation of the original MAGIC pointing approach...... which combined gaze tracking with a classical mouse device. The result of our experiment shows that the combination of eye and head movements is faster than head pointing for far targets and more accurate than eye pointing....

  19. Laser Dew-Point Hygrometer

    Science.gov (United States)

    Matsumoto, Shigeaki; Toyooka, Satoru

    1995-01-01

    A rough-surface-type automatic dew-point hygrometer was developed using a laser diode and an optical fiber cable. A gold plate with 0.8 µ m average surface roughness was used as a surface for deposition of dew to facilitate dew deposition and prevent supersaturation of water vapor at the dew point. It was shown experimentally that the quantity of dew deposited can be controlled to be constant at any predetermined level, and is independent of the dew point to be measured. The dew points were measured in the range from -15° C to 54° C in which the temperature ranged from 0° C to 60° C. The measurement error of the dew point was ±0.5° C which was equal to below ±2% in relative humidity in the above dew-point range.

  20. Fermat's point from five perspectives

    Science.gov (United States)

    Park, Jungeun; Flores, Alfinio

    2015-04-01

    The Fermat point of a triangle is the point such that minimizes the sum of the distances from that point to the three vertices. Five approaches to study the Fermat point of a triangle are presented in this article. First, students use a mechanical device using masses, strings and pulleys to study the Fermat point as the one that minimizes the potential energy of the system. Second, students use soap films between parallel planes connecting three pegs. The tension on the film will be minimal when the sum of distances is minimal. Third, students use an empirical approach, measuring distances in an interactive GeoGebra page. Fourth, students use Euclidean geometry arguments for two proofs based on the Torricelli configuration, and one using Viviani's Theorem. And fifth, the kinematic method is used to gain additional insight on the size of the angles between the segments joining the Fermat point with the vertices.

  1. The goal of ape pointing.

    Science.gov (United States)

    Halina, Marta; Liebal, Katja; Tomasello, Michael

    2018-01-01

    Captive great apes regularly use pointing gestures in their interactions with humans. However, the precise function of this gesture is unknown. One possibility is that apes use pointing primarily to direct attention (as in "please look at that"); another is that they point mainly as an action request (such as "can you give that to me?"). We investigated these two possibilities here by examining how the looking behavior of recipients affects pointing in chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). Upon pointing to food, subjects were faced with a recipient who either looked at the indicated object (successful-look) or failed to look at the indicated object (failed-look). We predicted that, if apes point primarily to direct attention, subjects would spend more time pointing in the failed-look condition because the goal of their gesture had not been met. Alternatively, we expected that, if apes point primarily to request an object, subjects would not differ in their pointing behavior between the successful-look and failed-look conditions because these conditions differed only in the looking behavior of the recipient. We found that subjects did differ in their pointing behavior across the successful-look and failed-look conditions, but contrary to our prediction subjects spent more time pointing in the successful-look condition. These results suggest that apes are sensitive to the attentional states of gestural recipients, but their adjustments are aimed at multiple goals. We also found a greater number of individuals with a strong right-hand than left-hand preference for pointing.

  2. Mathematical points as didactical ideas

    DEFF Research Database (Denmark)

    Mogensen, Arne

    Mathematics teaching in Denmark was recently recommended better organized in sequences with clear mathematical pedagogical goals and a focus on mathematical points. In this paper I define a mathematical point and inform on coding of transcripts in a video based Danish research study on grade 8 te...

  3. Review of NJ point system.

    Science.gov (United States)

    2013-03-01

    The purpose of this study is to investigate the comparative effectiveness of point-based versus incident-based : negligent driver monitoring systems and to explore how certain changes to the existing point-based system used in : New Jersey might impr...

  4. Heilbronn problem for five points

    International Nuclear Information System (INIS)

    Yang Lu; Zhang Jingzhong; Zeng Zhenbing

    1991-08-01

    Put 5 points in a unit square, then there must be at least one triangle, formed by three of these points, with an area not greater than √3/9. And the upper bound √3/9 is the best. Unexpectedly, this disproves an old conjecture posed twenty years ago. (author). 15 refs, 19 figs

  5. Model plant Key Measurement Points

    International Nuclear Information System (INIS)

    Schneider, R.A.

    1984-01-01

    For IAEA safeguards a Key Measurement Point is defined as the location where nuclear material appears in such a form that it may be measured to determine material flow or inventory. This presentation describes in an introductory manner the key measurement points and associated measurements for the model plant used in this training course

  6. Improved Dynamic Planar Point Location

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Arge, Lars; Georgiadis, Loukas

    2006-01-01

    We develop the first linear-space data structures for dynamic planar point location in general subdivisions that achieve logarithmic query time and poly-logarithmic update time.......We develop the first linear-space data structures for dynamic planar point location in general subdivisions that achieve logarithmic query time and poly-logarithmic update time....

  7. Cleaning Massive Sonar Point Clouds

    DEFF Research Database (Denmark)

    Arge, Lars Allan; Larsen, Kasper Green; Mølhave, Thomas

    2010-01-01

    We consider the problem of automatically cleaning massive sonar data point clouds, that is, the problem of automatically removing noisy points that for example appear as a result of scans of (shoals of) fish, multiple reflections, scanner self-reflections, refraction in gas bubbles, and so on. We...

  8. Endogenizing Prospect Theory's Reference Point

    OpenAIRE

    Ulrich Schmidt; Horst Zank

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This note provides a foundation of prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  9. The Philosophy of Turning Points

    DEFF Research Database (Denmark)

    Turcan, Romeo V.

    2013-01-01

    business and management field, the turning point is seen as a valuable unit of analysis within the research field. It is expected that this paper will encourage a dynamic scholarly conversation about the concept of turning point and how it can aid international business researchers in the development...

  10. Geodetic Control Points - Multi-State Control Point Database

    Data.gov (United States)

    NSGIC State | GIS Inventory — The Multi-State Control Point Database (MCPD) is a database of geodetic and mapping control covering Idaho and Montana. The control were submitted by registered land...

  11. Making Sense of Boiling Points and Melting Points

    Indian Academy of Sciences (India)

    GENERAL | ARTICLE. The boiling and melting points of a pure substance are char- ... bonds, which involves high energy and hence high temperatures. Among the .... with zero intermolecular force at all temperatures and pressures, which ...

  12. NOTE: Do acupuncture points exist?

    Science.gov (United States)

    Yan, Xiaohui; Zhang, Xinyi; Liu, Chenglin; Dang, Ruishan; Huang, Yuying; He, Wei; Ding, Guanghong

    2009-05-01

    We used synchrotron x-ray fluorescence analysis to probe the distribution of four chemical elements in and around acupuncture points, two located in the forearm and two in the lower leg. Three of the four acupuncture points showed significantly elevated concentrations of elements Ca, Fe, Cu and Zn in relation to levels in the surrounding tissue, with similar elevation ratios for Cu and Fe. The mapped distribution of these elements implies that each acupuncture point seems to be elliptical with the long axis along the meridian.

  13. PowerPoint 2013 bible

    CERN Document Server

    Wempen, Faithe

    2013-01-01

    Master PowerPoint and improve your presentation skills with one book! In today's business climate, you need to know PowerPoint inside and out, and that's not all. You also need to be able to make a presentation that makes an impact. From using sophisticated transitions and animation in your PowerPoint presentations to interfacing in person with your audience, this information-packed book helps you succeed. Start creating professional-quality slides that captivate audiences and discover essential tips and techniques for making first-rate presentations, whether you're at a podium or

  14. Calorimetry end-point predictions

    International Nuclear Information System (INIS)

    Fox, M.A.

    1981-01-01

    This paper describes a portion of the work presently in progress at Rocky Flats in the field of calorimetry. In particular, calorimetry end-point predictions are outlined. The problems associated with end-point predictions and the progress made in overcoming these obstacles are discussed. The two major problems, noise and an accurate description of the heat function, are dealt with to obtain the most accurate results. Data are taken from an actual calorimeter and are processed by means of three different noise reduction techniques. The processed data are then utilized by one to four algorithms, depending on the accuracy desired to determined the end-point

  15. Hawaii ESI: NESTS (Nest Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for seabird nesting colonies in coastal Hawaii. Vector points in this data set represent locations of...

  16. Parametric statistical change point analysis

    CERN Document Server

    Chen, Jie

    2000-01-01

    This work is an in-depth study of the change point problem from a general point of view and a further examination of change point analysis of the most commonly used statistical models Change point problems are encountered in such disciplines as economics, finance, medicine, psychology, signal processing, and geology, to mention only several The exposition is clear and systematic, with a great deal of introductory material included Different models are presented in each chapter, including gamma and exponential models, rarely examined thus far in the literature Other models covered in detail are the multivariate normal, univariate normal, regression, and discrete models Extensive examples throughout the text emphasize key concepts and different methodologies are used, namely the likelihood ratio criterion, and the Bayesian and information criterion approaches A comprehensive bibliography and two indices complete the study

  17. Control Point Generated PLS - lines

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Control Point Generated PLS layer contains line and polygon features to the 1/4 of 1/4 PLS section (approximately 40 acres) and government lot level. The layer...

  18. Detecting determinism from point processes.

    Science.gov (United States)

    Andrzejak, Ralph G; Mormann, Florian; Kreuz, Thomas

    2014-12-01

    The detection of a nonrandom structure from experimental data can be crucial for the classification, understanding, and interpretation of the generating process. We here introduce a rank-based nonlinear predictability score to detect determinism from point process data. Thanks to its modular nature, this approach can be adapted to whatever signature in the data one considers indicative of deterministic structure. After validating our approach using point process signals from deterministic and stochastic model dynamics, we show an application to neuronal spike trains recorded in the brain of an epilepsy patient. While we illustrate our approach in the context of temporal point processes, it can be readily applied to spatial point processes as well.

  19. Allegheny County Cell Tower Points

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset portrays cell tower locations as points in Allegheny County. The dataset is based on outbuilding codes in the Property Assessment Parcel Database used...

  20. Virginia ESI: REPTPT (Reptile Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for sea turtles in Virginia. Vector points in this data set represent nesting sites. Species-specific...

  1. Maryland ESI: NESTS (Nest Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for raptors in Maryland. Vector points in this data set represent bird nesting sites. Species-specific...

  2. Processing Terrain Point Cloud Data

    KAUST Repository

    DeVore, Ronald; Petrova, Guergana; Hielsberg, Matthew; Owens, Luke; Clack, Billy; Sood, Alok

    2013-01-01

    Terrain point cloud data are typically acquired through some form of Light Detection And Ranging sensing. They form a rich resource that is important in a variety of applications including navigation, line of sight, and terrain visualization

  3. Control Point Generated PLS - polygons

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Control Point Generated PLS layer contains line and polygon features to the 1/4 of 1/4 PLS section (approximately 40 acres) and government lot level. The layer...

  4. Calcareous Fens - Source Feature Points

    Data.gov (United States)

    Minnesota Department of Natural Resources — Pursuant to the provisions of Minnesota Statutes, section 103G.223, this database contains points that represent calcareous fens as defined in Minnesota Rules, part...

  5. Louisiana ESI: NESTS (Nest Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for seabird and wading bird nesting colonies in coastal Louisiana. Vector points in this data set represent...

  6. Some remarks on farthest points

    Czech Academy of Sciences Publication Activity Database

    Montesinos, V.; Zizler, P.; Zizler, Václav

    2011-01-01

    Roč. 105, č. 1 (2011), s. 119-131 ISSN 1578-7303 R&D Projects: GA AV ČR IAA100190901 Institutional research plan: CEZ:AV0Z10190503 Keywords : farthest points * strongly exposed points * generic differentiability * convex functions Subject RIV: BA - General Mathematics Impact factor: 0.340, year: 2011 http://link.springer.com/article/10.1007%2Fs13398-011-0012-z

  7. 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.

  8. WHO Standard Acupuncture Point Locations

    Directory of Open Access Journals (Sweden)

    Sabina Lim

    2010-01-01

    Full Text Available ‘WHO Standard Acupuncture Point Locations in the Western Pacific Region (WHO Standard was released in 2008. Initially, there were 92/361 controversial acupuncture points (acupoints. Through seven informal consultations and four task force team meetings, 86 points were agreed upon among the 92 controversial acupoints, leaving 6 remaining controversial acupoints, demanding active research in the future. This will enhance the reproducibility and validity of acupuncture studies. It will also lead to a better understanding of acupuncture mechanisms in order to optimize its clinical efficacy for a range of diseases and syndromes. This book has two parts: General Guidelines for Acupuncture Point Locations and WHO Standard Acupuncture Point Locations. First of all, familiarity with the General Guidelines for Acupuncture Point Locations in this book can help the reader to understand and use the contents of this book in depth. I would like to thank all of the participating experts and scholars for this great work, who have overcome the limits of previous acupuncture references. I also appreciate the dedicated effort and harmonious leadership of Dr Choi Seung-hoon, former Regional Adviser in Traditional Medicine of Western Pacific Office, WHO.

  9. Critical points in magnetic systems

    International Nuclear Information System (INIS)

    Bongaarts, A.L.M.

    1975-01-01

    The magnetical phase transitions of CsCoCl 3 .2H 2 O and CsCoCl 3 .2D 2 O are investigated by neutron diffraction techniques with special attention to the critical points in the phase diagrams. CsCoCl 3 .2H 2 O turned out to be a one-dimentional magnetic antiferromagnet with ferromagnetic and antiferromagnetic interactions. In the vicinity of the Neel point, the critical behavior in zero magnetic field could be described as a three-dimentional long range ordering, while the fluctuations in the system are one-dimensional. In the presence of a magnetic field, the behavior of the system in the critical region of the magnetic phase diagram between the Neel temperature at zero field (3.3degK) and 1.85degK, was in good agreement with the theory. Below 1.85degK, the phase transition in a magnetic field changes into a line of triple points whose end point could be identified as a tricritical point, i.e., an intersection of three critical lines. The parameters derived from observations in the neighborhood of this tricritical point obey the scaling laws but are not in numerical agreement with theoretical predictions

  10. Recent progress in fission at saddle point and scission point

    International Nuclear Information System (INIS)

    Blons, J.; Paya, D.; Signarbieux, C.

    High resolution measurements of 230 Th and 232 Th fission cross sections for neutrons exhibit a fine structure. Such a structure is interpreted as a superposition of two rotational bands in the third, asymmetric, well of the fission barrier. The fragment mass distribution in the thermal fission of 235 U and 233 U does not show any even-odd effect, even at the highest kinetic energies. This is the mark of a strong viscosity in the descent from saddle point to scission point [fr

  11. Digital microwave communication engineering point-to-point microwave systems

    CERN Document Server

    Kizer, George

    2013-01-01

    The first book to cover all engineering aspects of microwave communication path design for the digital age Fixed point-to-point microwave systems provide moderate-capacity digital transmission between well-defined locations. Most popular in situations where fiber optics or satellite communication is impractical, it is commonly used for cellular or PCS site interconnectivity where digital connectivity is needed but not economically available from other sources, and in private networks where reliability is most important. Until now, no book has adequately treated all en

  12. March 2003 Lidar Point Data of Southern California Coastline: Dana Point to Point La Jolla

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains lidar point data (Geodetic Coordinates) from a strip of Southern California coastline (including water, beach, cliffs, and top of cliffs) from...

  13. April 2004 Lidar Point Data of Southern California Coastline: Dana Point to Point La Jolla

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains lidar point data (Geodetic Coordinates) from a strip of Southern California coastline (including water, beach, cliffs, and top of cliffs) from...

  14. December 2002 Lidar Point Data of Southern California Coastline: Dana Point to Point La Jolla

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains lidar point data (latitude and longitude) from a strip of Southern California coastline (including water, beach, cliffs, and top of cliffs)...

  15. Dynamic magnetic x-points

    International Nuclear Information System (INIS)

    Leboeuf, J.N.; Tajima, T.; Dawson, J.M.

    1981-03-01

    Two-and-one-half dimensional magnetostatic and electromagnetic particle simulations of time-varying magnetic x-points and the associated plasma response are reported. The stability and topology depend on the crossing angle of the field lines at the x-point, irrespective of the plasma β. The electrostatic field and finite Larmor radius effects play an important role in current penetration and shaping of the plasma flow. The snapping of the field lines, and dragging of the plasma into, and confinement of the plasma at, an o-point (magnetic island) is observed. Magnetic island coalescence with explosive growth of the coalescence mode occurs and is accompanied by a large increase of kinetic energy and temperature as well as the formation of hot tails on the distribution functions

  16. Fixed points of quantum operations

    International Nuclear Information System (INIS)

    Arias, A.; Gheondea, A.; Gudder, S.

    2002-01-01

    Quantum operations frequently occur in quantum measurement theory, quantum probability, quantum computation, and quantum information theory. If an operator A is invariant under a quantum operation φ, we call A a φ-fixed point. Physically, the φ-fixed points are the operators that are not disturbed by the action of φ. Our main purpose is to answer the following question. If A is a φ-fixed point, is A compatible with the operation elements of φ? We shall show in general that the answer is no and we shall give some sufficient conditions under which the answer is yes. Our results will follow from some general theorems concerning completely positive maps and injectivity of operator systems and von Neumann algebras

  17. Fixed-point signal processing

    CERN Document Server

    Padgett, Wayne T

    2009-01-01

    This book is intended to fill the gap between the ""ideal precision"" digital signal processing (DSP) that is widely taught, and the limited precision implementation skills that are commonly required in fixed-point processors and field programmable gate arrays (FPGAs). These skills are often neglected at the university level, particularly for undergraduates. We have attempted to create a resource both for a DSP elective course and for the practicing engineer with a need to understand fixed-point implementation. Although we assume a background in DSP, Chapter 2 contains a review of basic theory

  18. Implementing floating-point DSP

    Czech Academy of Sciences Publication Activity Database

    Kadlec, Jiří; Chappel, S.

    2006-01-01

    Roč. 2, č. 3 (2006), s. 12-14 R&D Projects: GA AV ČR 1ET400750406; GA MŠk 1M0567 EU Projects: European Commission(XE) 027611 - AETHER Program:FP6 Institutional research plan: CEZ:AV0Z10750506 Keywords : PicoBlaze * floating point * FPGA Subject RIV: JC - Computer Hardware ; Software http://www.xilinx.com/publications/ magazines /emb_03/xc_pdf/p12-14_3emb-point.pdf

  19. Beyond the Point Ps Approximation

    OpenAIRE

    Stepanov, Sergey V.; Zvezhinskiy, Dmitry S.; Byakov, Vsevolod M.

    2012-01-01

    In application to positron annihilation spectroscopy, Ps atom is considered not as a point particle, but as a finite size e+ e- pair localized in a bubble-state in a medium. Variation of the internal Coulombic e+ -e- attraction vs. the bubble radius is estimated.

  20. Smooth random change point models.

    Science.gov (United States)

    van den Hout, Ardo; Muniz-Terrera, Graciela; Matthews, Fiona E

    2011-03-15

    Change point models are used to describe processes over time that show a change in direction. An example of such a process is cognitive ability, where a decline a few years before death is sometimes observed. A broken-stick model consists of two linear parts and a breakpoint where the two lines intersect. Alternatively, models can be formulated that imply a smooth change between the two linear parts. Change point models can be extended by adding random effects to account for variability between subjects. A new smooth change point model is introduced and examples are presented that show how change point models can be estimated using functions in R for mixed-effects models. The Bayesian inference using WinBUGS is also discussed. The methods are illustrated using data from a population-based longitudinal study of ageing, the Cambridge City over 75 Cohort Study. The aim is to identify how many years before death individuals experience a change in the rate of decline of their cognitive ability. Copyright © 2010 John Wiley & Sons, Ltd.

  1. The Mean as Balance Point

    Science.gov (United States)

    O'Dell, Robin S.

    2012-01-01

    There are two primary interpretations of the mean: as a leveler of data (Uccellini 1996, pp. 113-114) and as a balance point of a data set. Typically, both interpretations of the mean are ignored in elementary school and middle school curricula. They are replaced with a rote emphasis on calculation using the standard algorithm. When students are…

  2. Equations for arithmetic pointed tori

    NARCIS (Netherlands)

    Sijsling, J.R.

    2010-01-01

    In 1983, Kisao Takeuchi enumerated all 71 arithmetic (1;e)-groups. This is a special set of discrete subgroups of SL(2,R) of finite covolume and signature (1;e). The corresponding quotients of the upper half plane (called (1;e)-curves) have genus equal to 1 and a single elliptic point of order e.

  3. Flat Coalgebraic Fixed Point Logics

    Science.gov (United States)

    Schröder, Lutz; Venema, Yde

    Fixed point logics are widely used in computer science, in particular in artificial intelligence and concurrency. The most expressive logics of this type are the μ-calculus and its relatives. However, popular fixed point logics tend to trade expressivity for simplicity and readability, and in fact often live within the single variable fragment of the μ-calculus. The family of such flat fixed point logics includes, e.g., CTL, the *-nesting-free fragment of PDL, and the logic of common knowledge. Here, we extend this notion to the generic semantic framework of coalgebraic logic, thus covering a wide range of logics beyond the standard μ-calculus including, e.g., flat fragments of the graded μ-calculus and the alternating-time μ-calculus (such as ATL), as well as probabilistic and monotone fixed point logics. Our main results are completeness of the Kozen-Park axiomatization and a timed-out tableaux method that matches ExpTime upper bounds inherited from the coalgebraic μ-calculus but avoids using automata.

  4. Fixed points of quantum gravity

    OpenAIRE

    Litim, D F

    2003-01-01

    Euclidean quantum gravity is studied with renormalisation group methods. Analytical results for a non-trivial ultraviolet fixed point are found for arbitrary dimensions and gauge fixing parameter in the Einstein-Hilbert truncation. Implications for quantum gravity in four dimensions are discussed.

  5. ACS Photometric Zero Point Verification

    Science.gov (United States)

    Dolphin, Andrew

    2003-07-01

    The uncertainties in the photometric zero points create a fundamental limit to the accuracy of photometry. The current state of the ACS calibration is surprisingly poor, with zero point uncertainties of 0.03 magnitudes in the Johnson filters. The reason for this is that ACS observations of excellent ground-based standard fields, such as the omega Cen field used for WFPC2 calibrations, have not been obtained. Instead, the ACS photometric calibrations are based primarily on semi-emprical synthetic zero points and observations of fields too crowded for accurate ground-based photometry. I propose to remedy this problem by obtaining ACS broadband images of the omega Cen standard field with both the WFC and HRC. This will permit the direct determination of the ACS transformations, and is expected to double the accuracy to which the ACS zero points are known. A second benefit is that it will facilitate the comparison of the WFPC2 and ACS photometric systems, which will be important as WFPC2 is phased out and ACS becomes HST's primary imager.

  6. Determine point-to-point networking interactions using regular expressions

    Directory of Open Access Journals (Sweden)

    Konstantin S. Deev

    2015-06-01

    Full Text Available As Internet growth and becoming more popular, the number of concurrent data flows start to increasing, which makes sense in bandwidth requested. Providers and corporate customers need ability to identify point-to-point interactions. The best is to use special software and hardware implementations that distribute the load in the internals of the complex, using the principles and approaches, in particular, described in this paper. This paper represent the principles of building system, which searches for a regular expression match using computing on graphics adapter in server station. A significant computing power and capability to parallel execution on modern graphic processor allows inspection of large amounts of data through sets of rules. Using the specified characteristics can lead to increased computing power in 30…40 times compared to the same setups on the central processing unit. The potential increase in bandwidth capacity could be used in systems that provide packet analysis, firewalls and network anomaly detectors.

  7. Modelling point patterns with linear structures

    DEFF Research Database (Denmark)

    Møller, Jesper; Rasmussen, Jakob Gulddahl

    2009-01-01

    processes whose realizations contain such linear structures. Such a point process is constructed sequentially by placing one point at a time. The points are placed in such a way that new points are often placed close to previously placed points, and the points form roughly line shaped structures. We...... consider simulations of this model and compare with real data....

  8. Modelling point patterns with linear structures

    DEFF Research Database (Denmark)

    Møller, Jesper; Rasmussen, Jakob Gulddahl

    processes whose realizations contain such linear structures. Such a point process is constructed sequentially by placing one point at a time. The points are placed in such a way that new points are often placed close to previously placed points, and the points form roughly line shaped structures. We...... consider simulations of this model and compare with real data....

  9. Zero Point of Historical Time

    Directory of Open Access Journals (Sweden)

    R.S. Khakimov

    2014-02-01

    Full Text Available Historical studies are based on the assumption that there is a reference-starting point of the space-time – the Zero point of coordinate system. Due to the bifurcation in the Zero Point, the course of social processes changes sharply and the probabilistic causality replaces the deterministic one. For this reason, changes occur in the structure of social relations and statehood form as well as in the course of the ethnic processes. In such a way emerges a new discourse of the national behavior. With regard to the history of the Tatars and Tatarstan, such bifurcation points occurred in the periods of the formation: 1 of the Turkic Khaganate, which began to exist from the 6th century onward and became a qualitatively new State system that reformatted old elements in the new matrix introducing a new discourse of behavior; 2 of the Volga-Kama Bulgaria, where the rivers (Kama, Volga, Vyatka became the most important trade routes determining the singularity of this State. Here the nomadic culture was connected with the settled one and Islam became the official religion in 922; 3 and of the Golden Hordе, a powerful State with a remarkable system of communication, migration of huge human resources for thousands of kilometers, and extensive trade, that caused severe “mutations” in the ethnic terms and a huge mixing of ethnic groups. Given the dwelling space of Tatar population and its evolution within Russia, it can be argued that the Zero point of Tatar history, which conveyed the cultural invariants until today, begins in the Golden Horde. Neither in the Turkic khaganate nor in the Bulgar State, but namely in the Golden Horde. Despite the radical changes, the Russian Empire failed to transform the Tatars in the Russians. Therefore, contemporary Tatars preserved the Golden Horde tradition as a cultural invariant.

  10. Characterization of MIPAS elevation pointing

    Directory of Open Access Journals (Sweden)

    M. Kiefer

    2007-01-01

    Full Text Available Sufficient knowledge of the pointing is essential for analyses of limb emission measurements. The scientific retrieval processor for MIPAS on ENVISAT operated at IMK allows the retrieval of pointing information in terms of tangent altitudes along with temperature. The retrieved tangent altitudes are independent of systematic offsets in the engineering Line-Of-Sight (LOS information delivered with the ESA Level 1b product. The difference of pointing retrieved from the reprocessed high resolution MIPAS spectra and the engineering pointing information was examined with respect to spatial/temporal behaviour. Among others the following characteristics of MIPAS pointing could be identified: Generally the engineering tangent altitudes are too high by 0–1.8 km with conspicuous variations in this range over time. Prior to December of 2003 there was a drift of about 50–100 m/h, which was due to a slow change in the satellite attitude. A correction of this attitude is done twice a day, which leads to discontinuities in the order of 1–1.5 km in the tangent altitudes. Occasionally discontinuities up to 2.5 km are found, as already reported from MIPAS and SCIAMACHY observations. After an update of the orbit position software in December 2003 values of drift and jumps are much reduced. There is a systematic difference in the mispointing between the poles which amounts to 1.5–2 km, i.e. there is a conspicuous orbit-periodic feature. The analysis of the correlation between the instrument's viewing angle azimuth and differential mispointing supports the hypotheses that a major part of this latter phenomenon can be attributed to an error in the roll angle of the satellite/instrument system of approximately 42 mdeg. One conclusion is that ESA level 2 data should be compared to other data exclusively on tangent pressure levels. Complementary to IMK data, ESA operational LOS calibration results were used to characterize MIPAS pointing. For this purpose

  11. Femtosecond photoelectron point projection microscope

    International Nuclear Information System (INIS)

    Quinonez, Erik; Handali, Jonathan; Barwick, Brett

    2013-01-01

    By utilizing a nanometer ultrafast electron source in a point projection microscope we demonstrate that images of nanoparticles with spatial resolutions of the order of 100 nanometers can be obtained. The duration of the emission process of the photoemitted electrons used to make images is shown to be of the order of 100 fs using an autocorrelation technique. The compact geometry of this photoelectron point projection microscope does not preclude its use as a simple ultrafast electron microscope, and we use simple analytic models to estimate temporal resolutions that can be expected when using it as a pump-probe ultrafast electron microscope. These models show a significant increase in temporal resolution when comparing to ultrafast electron microscopes based on conventional designs. We also model the microscopes spectroscopic abilities to capture ultrafast phenomena such as the photon induced near field effect

  12. Sensing with Superconducting Point Contacts

    Directory of Open Access Journals (Sweden)

    Argo Nurbawono

    2012-05-01

    Full Text Available Superconducting point contacts have been used for measuring magnetic polarizations, identifying magnetic impurities, electronic structures, and even the vibrational modes of small molecules. Due to intrinsically small energy scale in the subgap structures of the supercurrent determined by the size of the superconducting energy gap, superconductors provide ultrahigh sensitivities for high resolution spectroscopies. The so-called Andreev reflection process between normal metal and superconductor carries complex and rich information which can be utilized as powerful sensor when fully exploited. In this review, we would discuss recent experimental and theoretical developments in the supercurrent transport through superconducting point contacts and their relevance to sensing applications, and we would highlight their current issues and potentials. A true utilization of the method based on Andreev reflection analysis opens up possibilities for a new class of ultrasensitive sensors.

  13. Leverage points for sustainability transformation.

    Science.gov (United States)

    Abson, David J; Fischer, Joern; Leventon, Julia; Newig, Jens; Schomerus, Thomas; Vilsmaier, Ulli; von Wehrden, Henrik; Abernethy, Paivi; Ives, Christopher D; Jager, Nicolas W; Lang, Daniel J

    2017-02-01

    Despite substantial focus on sustainability issues in both science and politics, humanity remains on largely unsustainable development trajectories. Partly, this is due to the failure of sustainability science to engage with the root causes of unsustainability. Drawing on ideas by Donella Meadows, we argue that many sustainability interventions target highly tangible, but essentially weak, leverage points (i.e. using interventions that are easy, but have limited potential for transformational change). Thus, there is an urgent need to focus on less obvious but potentially far more powerful areas of intervention. We propose a research agenda inspired by systems thinking that focuses on transformational 'sustainability interventions', centred on three realms of leverage: reconnecting people to nature, restructuring institutions and rethinking how knowledge is created and used in pursuit of sustainability. The notion of leverage points has the potential to act as a boundary object for genuinely transformational sustainability science.

  14. EBTR design-point selection

    International Nuclear Information System (INIS)

    Krakowski, R.A.; Bathke, C.G.

    1981-01-01

    The procedure used to select the design point for the ELMO Bumpy Torus Reactor (EBTR) study is described. The models used in each phase of the selection process are described, with an emphasis placed on the parametric design curves produced by each model. The tradeoffs related to burn physics, stability/equilibrium, electron-ring physics, and magnetics design are discussed. The resulting design point indicates a plasma with a 35-m major radius and a 1-m minor radium operating at an average core-plasma beta of 0.17, which at approx. 30 keV produces an average neutron wall loading of 1.4 MW/m 2 while maintaining key magnet (< 10 T) and total power (less than or equal to 4000 MWt) constraints

  15. The point of 6 sigma

    International Nuclear Information System (INIS)

    An, Yeong Jin

    2000-07-01

    This book gives descriptions of the point of 6 sigma. These are the titles of this : what 6 sigma is, sigma conception, motor roller 3.4 ppm, centering error, 6 sigma purpose, 6 sigma principle, eight steps of innovation strategy, 6 sigma innovation strategy of easy system step, measurement standard of 6 sigma outcome, the main role of 6 sigma, acknowledgment and reword, 6 sigma characteristic, 6 sigma effect, 6 sigma application and problems which happen when 6 sigma introduces.

  16. Change point analysis and assessment

    DEFF Research Database (Denmark)

    Müller, Sabine; Neergaard, Helle; Ulhøi, John Parm

    2011-01-01

    The aim of this article is to develop an analytical framework for studying processes such as continuous innovation and business development in high-tech SME clusters that transcends the traditional qualitative-quantitative divide. It integrates four existing and well-recognized approaches...... to studying events, processes and change, mamely change-point analysis, event-history analysis, critical-incident technique and sequence analysis....

  17. Turning points in reactor design

    International Nuclear Information System (INIS)

    Beckjord, E.S.

    1995-01-01

    This article provides some historical aspects on nuclear reactor design, beginning with PWR development for Naval Propulsion and the first commercial application at Yankee Rowe. Five turning points in reactor design and some safety problems associated with them are reviewed: (1) stability of Dresden-1, (2) ECCS, (3) PRA, (4) TMI-2, and (5) advanced passive LWR designs. While the emphasis is on the thermal-hydraulic aspects, the discussion is also about reactor systems

  18. Turning points in reactor design

    Energy Technology Data Exchange (ETDEWEB)

    Beckjord, E.S.

    1995-09-01

    This article provides some historical aspects on nuclear reactor design, beginning with PWR development for Naval Propulsion and the first commercial application at Yankee Rowe. Five turning points in reactor design and some safety problems associated with them are reviewed: (1) stability of Dresden-1, (2) ECCS, (3) PRA, (4) TMI-2, and (5) advanced passive LWR designs. While the emphasis is on the thermal-hydraulic aspects, the discussion is also about reactor systems.

  19. Viviani Polytopes and Fermat Points

    Science.gov (United States)

    Zhou, Li

    2012-01-01

    Given a set of oriented hyperplanes P = {p1, . . . , pk} in R[superscript n], define v : R[superscript n] [right arrow] R by v(X) = the sum of the signed distances from X to p[subscript 1], . . . , p[subscript k], for any point X [is a member of] R[superscript n]. We give a simple geometric characterization of P for which v is constant, leading to…

  20. A fixed-point farrago

    CERN Document Server

    Shapiro, Joel H

    2016-01-01

    This text provides an introduction to some of the best-known fixed-point theorems, with an emphasis on their interactions with topics in analysis. The level of exposition increases gradually throughout the book, building from a basic requirement of undergraduate proficiency to graduate-level sophistication. Appendices provide an introduction to (or refresher on) some of the prerequisite material and exercises are integrated into the text, contributing to the volume’s ability to be used as a self-contained text. Readers will find the presentation especially useful for independent study or as a supplement to a graduate course in fixed-point theory. The material is split into four parts: the first introduces the Banach Contraction-Mapping Principle and the Brouwer Fixed-Point Theorem, along with a selection of interesting applications; the second focuses on Brouwer’s theorem and its application to John Nash’s work; the third applies Brouwer’s theorem to spaces of infinite dimension; and the fourth rests ...

  1. Zero-point oscillations, zero-point fluctuations, and fluctuations of zero-point oscillations

    International Nuclear Information System (INIS)

    Khalili, Farit Ya

    2003-01-01

    Several physical effects and methodological issues relating to the ground state of an oscillator are considered. Even in the simplest case of an ideal lossless harmonic oscillator, its ground state exhibits properties that are unusual from the classical point of view. In particular, the mean value of the product of two non-negative observables, kinetic and potential energies, is negative in the ground state. It is shown that semiclassical and rigorous quantum approaches yield substantially different results for the ground state energy fluctuations of an oscillator with finite losses. The dependence of zero-point fluctuations on the boundary conditions is considered. Using this dependence, it is possible to transmit information without emitting electromagnetic quanta. Fluctuations of electromagnetic pressure of zero-point oscillations are analyzed, and the corresponding mechanical friction is considered. This friction can be viewed as the most fundamental mechanism limiting the quality factor of mechanical oscillators. Observation of these effects exceeds the possibilities of contemporary experimental physics but almost undoubtedly will be possible in the near future. (methodological notes)

  2. Point-point and point-line moving-window correlation spectroscopy and its applications

    Science.gov (United States)

    Zhou, Qun; Sun, Suqin; Zhan, Daqi; Yu, Zhiwu

    2008-07-01

    In this paper, we present a new extension of generalized two-dimensional (2D) correlation spectroscopy. Two new algorithms, namely point-point (P-P) correlation and point-line (P-L) correlation, have been introduced to do the moving-window 2D correlation (MW2D) analysis. The new method has been applied to a spectral model consisting of two different processes. The results indicate that P-P correlation spectroscopy can unveil the details and re-constitute the entire process, whilst the P-L can provide general feature of the concerned processes. Phase transition behavior of dimyristoylphosphotidylethanolamine (DMPE) has been studied using MW2D correlation spectroscopy. The newly proposed method verifies that the phase transition temperature is 56 °C, same as the result got from a differential scanning calorimeter. To illustrate the new method further, a lysine and lactose mixture has been studied under thermo perturbation. Using the P-P MW2D, the Maillard reaction of the mixture was clearly monitored, which has been very difficult using conventional display of FTIR spectra.

  3. The Point Lepreau Desktop Simulator

    International Nuclear Information System (INIS)

    MacLean, M.; Hogg, J.; Newman, H.

    1997-01-01

    The Point Lepreau Desktop Simulator runs plant process modeling software on a 266 MHz single CPU DEC Alpha computer. This same Alpha also runs the plant control computer software on an SSCI 125 emulator. An adjacent Pentium PC runs the simulator's Instructor Facility software, and communicates with the Alpha through an Ethernet. The Point Lepreau Desktop simulator is constructed to be as similar as possible to the Point Lepreau full scope training simulator. This minimizes total maintenance costs and enhances the benefits of the desktop simulator. Both simulators have the same modeling running on a single CPU in the same schedule of calculations. Both simulators have the same Instructor Facility capable of developing and executing the same lesson plans, doing the same monitoring and control of simulations, inserting all the same malfunctions, performing all the same overrides, capable of making and restoring all the same storepoints. Both simulators run the same plant control computer software - the same assembly language control programs as the power plant uses for reactor control, heat transport control, annunciation, etc. This is a higher degree of similarity between a desktop simulator and a full scope training simulator than previously reported for a computer controlled nuclear plant. The large quantity of control room hardware missing from the desktop simulator is replaced by software. The Instructor Facility panel override software of the training simulator provides the means by which devices (switches, controllers, windows, etc.) on the control room panels can be controlled and monitored in the desktop simulator. The CRT of the Alpha provides a mouse operated DCC keyboard mimic for controlling the plant control computer emulation. Two emulated RAMTEK display channels appear as windows for monitoring anything of interest on plant DCC displays, including one channel for annunciation. (author)

  4. Growth points in nuclear physics

    CERN Document Server

    Hodgson, Peter Edward

    1980-01-01

    Growth Points in Nuclear Physics, Volume 2 covers the progress in the fields of nuclear structure and nuclear reactions. This book is composed of three chapters. The first chapter is devoted to nuclear forces and potentials, in particular the optical model potential that enables the elastic scattering of many particles by nuclei to be calculated in a very simple manner. This chapter also deals with the three-body forces and the spin dependence of the nuclear potential. The second chapter describes higher order processes involving two or more stages, specifically their intrinsic interest and th

  5. Processing Terrain Point Cloud Data

    KAUST Repository

    DeVore, Ronald

    2013-01-10

    Terrain point cloud data are typically acquired through some form of Light Detection And Ranging sensing. They form a rich resource that is important in a variety of applications including navigation, line of sight, and terrain visualization. Processing terrain data has not received the attention of other forms of surface reconstruction or of image processing. The goal of terrain data processing is to convert the point cloud into a succinct representation system that is amenable to the various application demands. The present paper presents a platform for terrain processing built on the following principles: (i) measuring distortion in the Hausdorff metric, which we argue is a good match for the application demands, (ii) a multiscale representation based on tree approximation using local polynomial fitting. The basic elements held in the nodes of the tree can be efficiently encoded, transmitted, visualized, and utilized for the various target applications. Several challenges emerge because of the variable resolution of the data, missing data, occlusions, and noise. Techniques for identifying and handling these challenges are developed. © 2013 Society for Industrial and Applied Mathematics.

  6. Address Points - COUNTY_ADDRESS_POINTS_IDHS_IN: Address Points Maintained by County Agencies in Indiana (Indiana Department of Homeland Security, Point feature class)

    Data.gov (United States)

    NSGIC State | GIS Inventory — COUNTY_ADDRESS_POINTS_IDHS_IN is an ESRI Geodatabase point feature class that contains address points maintained by county agencies in Indiana, provided by personnel...

  7. Glacial Features (Point) - Quad 168 (EPPING, NH)

    Data.gov (United States)

    University of New Hampshire — The Glacial Features (Point) layer describes point features associated with surficial geology. These glacial features include, but are not limited to, delta forsets,...

  8. Possible refurbishment of Point Lepreau

    International Nuclear Information System (INIS)

    White, R.M.; Groom, S.H.; Thompson, P.D.; Barclay, J.M.; Allen, P.J.

    2001-01-01

    In February 2000, the NB Power Board of Directors approved Phase one of a project to produce a business case including a detailed scope and estimate associated with the possible refurbishment of the Point Lepreau Generating Station (PLGS). The Preliminary plan for refurbishment projects an 18-month outage starting as early as the spring of 2006. If the station were to be refurbished, then it would be run for another 25 to 30 years. The decision on whether or not to refurbish PLGS has not been made and is not expected until the summer of 2002. The results of the first phase of the project will be used to prepare a detailed business case that will be presented to the NB Power board of directors in January of 2002. At that time a decision will be made as to whether to refurbish the unit, or obtain other means of replacing the energy produced by PLGS. The station currently produces about a third of the power generated within the province. If the business case is approved, all-380 Pressure Tubes and Calandria Tubes, along with their related End Fittings and Feeders would be replaced. This material would be stored in new storage vaults to be constructed at the existing on-site Waste Management Facility. Replacement of other station components will be performed as required, as determined from the results of a comprehensive Plant Condition Assessment. The condition assessments build on work done under the Plant Life Management Program. Point Lepreau Generating Station has operated well since start of commercial operation in early 1983. With a lifetime capacity factor of about 84% (up to the end of 2000), it has proven to be an economic and environmentally sound electricity provider. The station has also had a significant positive economic impact in Southern New Brunswick, employing over 600 people. However the Pressure Tubes and Feeders are nearing the point in time in which they will exceed their fitness for service criteria. Although tubes can be replaced on an

  9. Possible refurbishment of Point Lepreau

    International Nuclear Information System (INIS)

    White, R.M.; Groom, S.H.; Thompson, P.D.; Barclay, J.M.; Allen, P.J.

    2001-01-01

    In February 2000, the NB Power Board of Directors approved Phase one of a project to produce a business case including a detailed scope and estimate associated with the possible refurbishment of the Point Lepreau Generating Station (PLGS). The Preliminary plan for refurbishment projects an 18-month outage starting as early as the spring of 2006. If the station were to be refurbished, then it would be run for another 25 to 30 years. The decision on whether or not to refurbish PLGS has not been made and is not expected until the summer of 2002. The results of the first phase of the project will be used to prepare a detailed business case that will be presented to the NB Power board of directors in January of 2002. At that time a decision will be made as to whether to refurbish the unit, or obtain other means of replacing the energy produced by PLGS. The station currently produces about a third of the power generated within the province. If the business case is approved, all-380 Pressure Tubes and Calandria Tubes, along with their related End Fittings and Feeders would be replaced. This material would be stored in new storage vaults to be constructed at the existing on-site Waste Management Facility. Replacement of other station components will be performed as required, as determined from the results of a comprehensive Plant Condition Assessment. The condition assessments build on work done under the Plant Life Management Program. Point Lepreau Generating Station has operated well since start of commercial operation in early 1983. With a lifetime capacity factor of about 84% (up to the end of 2000), it has proven to be an economic and environmentally sound electricity provider. The station has also had a significant positive economic impact in Southern New Brunswick, employing over 600 people. However the Pressure Tubes and Feeders are nearing the point in time in which they will exceed their fitness for service criteria. Although tubes can be replaced on an

  10. Rational points on elliptic curves

    CERN Document Server

    Silverman, Joseph H

    2015-01-01

    The theory of elliptic curves involves a pleasing blend of algebra, geometry, analysis, and number theory. This book stresses this interplay as it develops the basic theory, thereby providing an opportunity for advanced undergraduates to appreciate the unity of modern mathematics. At the same time, every effort has been made to use only methods and results commonly included in the undergraduate curriculum. This accessibility, the informal writing style, and a wealth of exercises make Rational Points on Elliptic Curves an ideal introduction for students at all levels who are interested in learning about Diophantine equations and arithmetic geometry. Most concretely, an elliptic curve is the set of zeroes of a cubic polynomial in two variables. If the polynomial has rational coefficients, then one can ask for a description of those zeroes whose coordinates are either integers or rational numbers. It is this number theoretic question that is the main subject of this book. Topics covered include the geometry and ...

  11. The physics of exceptional points

    International Nuclear Information System (INIS)

    Heiss, W D

    2012-01-01

    A short résumé is given about the nature of exceptional points (EPs) followed by discussions about their ubiquitous occurrence in a great variety of physical problems. EPs feature in classical as well as in quantum mechanical problems. They are associated with symmetry breaking for PT-symmetric Hamiltonians, where a great number of experiments has been performed, in particular in optics, and to an increasing extent in atomic and molecular physics. EPs are involved in quantum phase transition and quantum chaos; they produce dramatic effects in multichannel scattering, specific time dependence and more. In nuclear physics, they are associated with instabilities and continuum problems. Being spectral singularities they also affect approximation schemes. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Quantum physics with non-Hermitian operators’. (paper)

  12. Photovoltaics at Point Pelee Park

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    Case study of an Ontario Hydro-installed photovoltaic system at Point Pelee Park, a bird sanctuary located on Lake Erie, is described. The system consists of a 1080 W photovoltaic array used to supply electricity to one of the washrooms. The cost for installing the system was $30,000 which was considerably cheaper than the $100,000 estimate for an underground power line. The independent system is the only source of energy for the washroom, therefore it was necessary to reduce the total electrical demand required by the facility. Electricity was used for the water pump, chlorinator and lighting. Motion sensors were installed to further reduce electrical demand. Washroom heaters were converted to propane. 2 figs.

  13. Preferred design of transfer points

    Energy Technology Data Exchange (ETDEWEB)

    Firstbrook, J

    1983-06-01

    The paper reports the results of a study carried out at MRDE on the performance of transfer points. These sites still require a considerable deployment of manpower. The investigations were divided into 3 main sections: mineral handling; chute design; belt cleaning and spillage conveying. In order to achieve a sufficient level of reliability of a transfer system, it is considered that the coal size should not be greater than 250 mm. Different designs of gravity transfer chute were studied and 3 basic designs emerged as being effective : dump chute, curved site entry, and asymmetric side entry. Selection is dependent on conveyor sizes, speeds, and mineral throughput. Individual belt cleaners are not sufficient to clean belts carrying typical run-of-mine material: two cleaners followed by a set of squeeze rollers are recommended. Several designs of spillage conveyor were investigated; at the present time the electro/hydraulic type appears to be the most satisfactory.

  14. Point-source inversion techniques

    Science.gov (United States)

    Langston, Charles A.; Barker, Jeffrey S.; Pavlin, Gregory B.

    1982-11-01

    A variety of approaches for obtaining source parameters from waveform data using moment-tensor or dislocation point source models have been investigated and applied to long-period body and surface waves from several earthquakes. Generalized inversion techniques have been applied to data for long-period teleseismic body waves to obtain the orientation, time function and depth of the 1978 Thessaloniki, Greece, event, of the 1971 San Fernando event, and of several events associated with the 1963 induced seismicity sequence at Kariba, Africa. The generalized inversion technique and a systematic grid testing technique have also been used to place meaningful constraints on mechanisms determined from very sparse data sets; a single station with high-quality three-component waveform data is often sufficient to discriminate faulting type (e.g., strike-slip, etc.). Sparse data sets for several recent California earthquakes, for a small regional event associated with the Koyna, India, reservoir, and for several events at the Kariba reservoir have been investigated in this way. Although linearized inversion techniques using the moment-tensor model are often robust, even for sparse data sets, there are instances where the simplifying assumption of a single point source is inadequate to model the data successfully. Numerical experiments utilizing synthetic data and actual data for the 1971 San Fernando earthquake graphically demonstrate that severe problems may be encountered if source finiteness effects are ignored. These techniques are generally applicable to on-line processing of high-quality digital data, but source complexity and inadequacy of the assumed Green's functions are major problems which are yet to be fully addressed.

  15. Point to point multispectral light projection applied to cultural heritage

    Science.gov (United States)

    Vázquez, D.; Alvarez, A.; Canabal, H.; Garcia, A.; Mayorga, S.; Muro, C.; Galan, T.

    2017-09-01

    Use of new of light sources based on LED technology should allow the develop of systems that combine conservation and exhibition requirements and allow to make these art goods available to the next generations according to sustainability principles. The goal of this work is to develop light systems and sources with an optimized spectral distribution for each specific point of the art piece. This optimization process implies to maximize the color fidelity reproduction and the same time to minimize the photochemical damage. Perceived color under these sources will be similar (metameric) to technical requirements given by the restoration team uncharged of the conservation and exhibition of the goods of art. Depending of the fragility of the exposed art objects (i.e. spectral responsivity of the material) the irradiance must be kept under a critical level. Therefore, it is necessary to develop a mathematical model that simulates with enough accuracy both the visual effect of the illumination and the photochemical impact of the radiation. Spectral reflectance of a reference painting The mathematical model is based on a merit function that optimized the individual intensity of the LED-light sources taking into account the damage function of the material and color space coordinates. Moreover the algorithm used weights for damage and color fidelity in order to adapt the model to a specific museal application. In this work we show a sample of this technology applied to a picture of Sorolla (1863-1923) an important Spanish painter title "woman walking at the beach".

  16. Acid dew point measurement in flue gases

    Energy Technology Data Exchange (ETDEWEB)

    Struschka, M.; Baumbach, G.

    1986-06-01

    The operation of modern boiler plants requires the continuous measurement of the acid dew point in flue gases. An existing measuring instrument was modified in such a way that it can determine acid dew points reliably, reproduceably and continuously. The authors present the mechanisms of the dew point formation, the dew point measuring principle, the modification and the operational results.

  17. 18 CFR 157.211 - Delivery points.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Delivery points. 157... for Certain Transactions and Abandonment § 157.211 Delivery points. (a) Construction and operation—(1... delivery point, excluding the construction of certain delivery points subject to the prior notice...

  18. Professional SharePoint 2010 Development

    CERN Document Server

    Rizzo, Tom; Fried, Jeff

    2010-01-01

    Learn to leverage the features of the newest version of SharePoint, in this update to the bestseller. More than simply a portal, SharePoint is Microsoft's popular content management solution for building intranets and Web sites 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 one of the most recognized names in SharePoint development, Professional SharePoint 2010 Development offers an

  19. MOVING WINDOW SEGMENTATION FRAMEWORK FOR POINT CLOUDS

    Directory of Open Access Journals (Sweden)

    G. Sithole

    2012-07-01

    Full Text Available As lidar point clouds become larger streamed processing becomes more attractive. This paper presents a framework for the streamed segmentation of point clouds with the intention of segmenting unstructured point clouds in real-time. The framework is composed of two main components. The first component segments points within a window shifting over the point cloud. The second component stitches the segments within the windows together. In this fashion a point cloud can be streamed through these two components in sequence, thus producing a segmentation. The algorithm has been tested on airborne lidar point cloud and some results of the performance of the framework are presented.

  20. Yield point of metallic glass

    International Nuclear Information System (INIS)

    Shimizu, Futoshi; Ogata, Shigenobu; Li, Ju

    2006-01-01

    Shear bands form in most bulk metallic glasses (BMGs) within a narrow range of uniaxial strain ε y ≅ 2%. We propose this critical condition corresponds to embryonic shear band (ESB) propagation, not its nucleation. To propagate an ESB, the far-field shear stress τ ∞ ∼ Eε y /2 must exceed the quasi-steady-state glue traction τ glue of shear-alienated glass until the glass transition temperature is approached internally due to frictional heating, at which point ESB matures as a runaway shear crack. The incubation length scale l inc necessary for this maturation is estimated to be ∼10 2 nm for Zr-based BMGs, below which sample size-scale shear localization does not happen. In shear-alienated glass, the last resistance against localized shearing comes from extremely fast downhill dissipative dynamics of timescale comparable to atomic vibrations, allowing molecular dynamics (MD) simulations to capture this recovery process which governs τ glue . We model four metallic glasses: a binary Lennard-Jones system, two binary embedded atom potential systems and a quinternary embedded atom system. Despite vast differences in the structure and interatomic interactions, the four MD calculations give ε y predictions of 2.4%, 2.1%, 2.6% and 2.9%, respectively

  1. Anesthesiology Point of Care project.

    Science.gov (United States)

    McDonald, John S; Noback, Carl R; Cheng, Drew; Lee, T K; Nenov, Val

    2002-01-01

    We are developing a dynamic prototype visual communication system for the operating room environs. This has classically been viewed as an isolated and impenetrable workplace. All medical experiences and all teaching remain in a one to one closed loop with no recall or subsequent sharing for the training and education of other colleagues. The "Anesthesia Point of Care" (APOC) concept embraces the sharing of, recording of, and presentation of various physiological and pharmacological events so that real time memory can be shared at a later time for the edification of other colleagues who were not present at the time of the primary learning event. In addition it also provides a remarkably rapid tool for fellow faculty to respond to obvious stress and crisis events that can be broadcast instantly at the time of happening. Finally, it also serves as an efficient and effective means of paging and general communication throughout the daily routines among various healthcare providers in anesthesiology who work as a team unit; these include the staff, residents, CRNAs, physician assistants, and technicians. This system offers a unique opportunity to eventually develop future advanced ideas that can include training exercises, presurgical evaluations, surgical scheduling and improvements in efficiency based upon earlier than expected case completion or conversely later than expected case completion and even as a unique window to development of improved billing itemization and coordination.

  2. Decision Point 1 Topical Report

    Energy Technology Data Exchange (ETDEWEB)

    Yablonsky, Al; Barsoumian, Shant; Legere, David

    2013-05-01

    This Topical Report addresses accomplishments achieved during Phase 2a of the SkyMine® Carbon Mineralization Pilot Project. The primary objectives of this project are to design, construct, and operate a system to capture CO2 from a slipstream of flue gas from a commercial coal-fired cement kiln, convert that CO2 to products having commercial value (i.e., beneficial use), show the economic viability of the CO2 capture and conversion process, and thereby advance the technology to the point of readiness for commercial scale demonstration and proliferation. The overall process is carbon negative, resulting in mineralization of CO2 that would otherwise be released into the atmosphere. The project will also substantiate market opportunities for the technology by sales of chemicals into existing markets, and identify opportunities to improve technology performance and reduce costs at the commercial scale. The project is being conducted in two phases. The primary objectives of Phase 1 were to elaborate proven SkyMine® process chemistry to commercial pilot-scale operation and complete the preliminary design for the pilot plant to be built and operated in Phase 2, complete a NEPA evaluation, and develop a comprehensive carbon life cycle analysis. The objective of the current Phase (2a) is to complete the detailed design of the pilot plant to be built in Phase 2b.

  3. Gravity and Zero Point Energy

    Science.gov (United States)

    Massie, U. W.

    When Planck introduced the 1/2 hv term to his 1911 black body equation he showed that there is a residual energy remaining at zero degree K after all thermal energy ceased. Other investigators, including Lamb, Casimir, and Dirac added to this information. Today zero point energy (ZPE) is accepted as an established condition. The purpose of this paper is to demonstrate that the density of the ZPE is given by the gravity constant (G) and the characteristics of its particles are revealed by the cosmic microwave background (CMB). Eddies of ZPE particles created by flow around mass bodies reduce the pressure normal to the eddy flow and are responsible for the force of gravity. Helium atoms resonate with ZPE particles at low temperature to produce superfluid helium. High velocity micro vortices of ZPE particles about a basic particle or particles are responsible for electromagnetic forces. The speed of light is the speed of the wave front in the ZPE and its value is a function of the temperature and density of the ZPE.

  4. Tipping Points, Great and Small

    Science.gov (United States)

    Morrison, Foster

    2010-12-01

    The Forum by Jordan et al. [2010] addressed environmental problems of various scales in great detail, but getting the critical message through to the formulators of public policies requires going back to basics, namely, that exponential growth (of a population, an economy, or most anything else) is not sustainable. When have you heard any politician or economist from anywhere across the ideological spectrum say anything other than that more growth is essential? There is no need for computer models to demonstrate “limits to growth,” as was done in the 1960s. Of course, as one seeks more details, the complexity of modeling will rapidly outstrip the capabilities of both observation and computing. This is common with nonlinear systems, even simple ones. Thus, identifying all possible “tipping points,” as suggested by Jordan et al. [2010], and then stopping just short of them, is impractical if not impossible. The main thing needed to avoid environmental disasters is a bit of common sense.

  5. Turkey Point tritium. Progress report

    International Nuclear Information System (INIS)

    Ostlund, H.G.; Dorsey, H.G.

    1976-01-01

    In 1972-73 the Florida Power and Light Company (FPL) began operation of two nuclear reactors at Turkey Point on lower Biscayne Bay. One radioactive by-product resulting from the operation of the nuclear reactors, tritium, provides a unique opportunity to study transport and exchange processes on a local scale. Since the isotope in the form of water is not removed from the liquid effluent, it is discharged to the cooling canal system. By studying its residence time in the canal and the pathways by which it leaves the canals, knowledge of evaporative process, groundwater movement, and bay exchange with the ocean can be obtained. Preliminary results obtained from measurement of tritium levels, both in the canal system and in the surrounding environment are discussed. Waters in lower Biscayne Bay and Card and Barnes Sounds receive only a small portion of the total tritium produced by the nuclear plant. The dominating tritium loss most likely is through evaporation from the canals. The capability of measuring extremely low HTO levels allows the determination of the evaporation rate experimentally by measuring the tritium levels of air after having passed over the canals

  6. Beginning SharePoint 2010 Administration Windows SharePoint Foundation 2010 and Microsoft SharePoint Server 2010

    CERN Document Server

    Husman, Göran

    2010-01-01

    Complete coverage on the latest advances in SharePoint 2010 administration. SharePoint 2010 comprises an abundance of new features, and this book shows you how to take advantage of all SharePoint 2010's many improvements. Written by a four-time SharePoint MVP, Beginning SharePoint 2010 Administration begins with a comparison of SharePoint 2010 compared to the previous version and then examines the differences between WSS 4.0 and MSS 2010. Packed with step-by-step instructions, tips and tricks, and real-world examples, this book dives into the basics of how to install, manage, and administrate

  7. Comparison of Dose When Prescribed to Point A and Point H for Brachytherapy in Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gang, Ji Hyeong; Gim, Il Hwan; Hwang, Seon Boong; Kim, Woong; Im, Hyeong Seo; Gang, Jin Mook; Gim, Gi Hwan; Lee, Ah Ram [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seou (Korea, Republic of)

    2012-09-15

    The purpose of this study is to compare plans prescribed to point A with these prescribed to point H recommended by ABS (American Brachytherapy Society) in high dose rate intracavitary brachytherapy for cervical carcinoma. This study selected 103 patients who received HDR (High Dose Rate) brachytherapy using tandem and ovoids from March 2010 to January 2012. Point A, bladder point, and rectal point conform with Manchester System. Point H conforms with ABS recommendation. Also Sigmoid colon point, and vagina point were established arbitrarily. We examined distance between point A and point H. The percent dose at point A was calculated when 100% dose was prescribed to point H. Additionally, the percent dose at each reference points when dose is prescribed to point H and point A were calculated. The relative dose at point A was lower when point H was located inferior to point A. The relative doses at bladder, rectal, sigmoid colon, and vagina points were higher when point H was located superior to point A, and lower when point H was located inferior to point A. This study found out that as point H got located much superior to point A, the absorbed dose of surrounding normal organs became higher, and as point H got located much inferior to point A, the absorbed dose of surrounding normal organs became lower. This differences dose not seem to affect the treatment. However, we suggest this new point is worth being considered for the treatment of HDR if dose distribution and absorbed dose at normal organs have large differences between prescribed to point A and H.

  8. Point Lepreau refurbishment - update 5

    International Nuclear Information System (INIS)

    White, R.M.; Eagles, E.R.; Hickman, C.N.; Baker, R.; Thompson, P.D.; Howieson, J.Q.; Ichiyen, N.

    2005-01-01

    NB Power Nuclear is planning to conduct a 18-month maintenance outage of the Point Lepreau Generating Station (PLGS) beginning in April 2008. The major activity would be the replacement of all 380 Fuel Channel and Calandria Tube assemblies and connecting feeder pipes. This activity is referred to as Retube. NB Power Nuclear would also take advantage of this outage to conduct a number of repairs, replacements, inspection and upgrades (such as rewinding or replacing the generator, replacement of shutdown system trip computers, replacement of certain valves and expansion joints, inspection of systems not normally accessible, etc.). These collective activities are referred to as Refurbishment. This would allow the station to operate for an additional 25 to 30 years. The scope or the project was determined [mm the outcome of a two year study involving a detailed condition assessment of the station which examined Issues relating to ageing and obsolescence, along with a detailed review or Safety and Licensing issues associated with extended operation. The Refurbishment outage would be preceded by a detailed Engineering Project Phase that would: Finalize details of the Retube process including modeling, tooling development, site facilities and training of personnel. Perform necessary engineering activities related to design modifications. Construct the new waste storage structures to house Retube Waste and other additional waste storage structures for the extended life of the station. Setup necessary temporary construction facilities (offices, storage areas, change moms, decontamination an maintenance areas) to support Retube. Procure equipment and components. Perform detailed outage planning. Initiate development of detailed commissioning as well as lay-up, monitoring and return to service procedures. At the present time, the NB Power Nuclear Board of Directors and the New Brunswick Provincial government are reviewing a proposal for a lease arrangement from Bruce Power

  9. Professional SharePoint 2010 Administration

    CERN Document Server

    Klindt, Todd; Caravajal, Steve

    2010-01-01

    Thorough coverage of the improvements and changes to SharePoint 2010. SharePoint 2010 boasts a variety of incredible new features that will challenge even the most experienced administrator who is upgrading from SharePoint 2007. Written by a team of SharePoint experts, this book places a takes aim at showing you how to make these new features work right for you. Offering an in-depth look at SharePoint 2010, the authors focus on how SharePoint functionality has changed from its earliest version to its newest, and they provide you with detailed coverage of all the new features and capabilities.:

  10. 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

  11. 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

  12. 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

  13. 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

  14. Testing Local Independence between Two Point Processes

    DEFF Research Database (Denmark)

    Allard, Denis; Brix, Anders; Chadæuf, Joël

    2001-01-01

    Independence test, Inhomogeneous point processes, Local test, Monte Carlo, Nonstationary, Rotations, Spatial pattern, Tiger bush......Independence test, Inhomogeneous point processes, Local test, Monte Carlo, Nonstationary, Rotations, Spatial pattern, Tiger bush...

  15. State Wildlife Management Area Public Facilities - points

    Data.gov (United States)

    Minnesota Department of Natural Resources — This point theme contains facilities and features for WMAs that are best represented as points. WMAs are part of the Minnesota state recreation system created to...

  16. Implementation of Steiner point of fuzzy set.

    Science.gov (United States)

    Liang, Jiuzhen; Wang, Dejiang

    2014-01-01

    This paper deals with the implementation of Steiner point of fuzzy set. Some definitions and properties of Steiner point are investigated and extended to fuzzy set. This paper focuses on establishing efficient methods to compute Steiner point of fuzzy set. Two strategies of computing Steiner point of fuzzy set are proposed. One is called linear combination of Steiner points computed by a series of crisp α-cut sets of the fuzzy set. The other is an approximate method, which is trying to find the optimal α-cut set approaching the fuzzy set. Stability analysis of Steiner point of fuzzy set is also studied. Some experiments on image processing are given, in which the two methods are applied for implementing Steiner point of fuzzy image, and both strategies show their own advantages in computing Steiner point of fuzzy set.

  17. The Science of Drug Use: Discussion Points

    Science.gov (United States)

    ... The Science of Drug Use: Discussion Points The Science of Drug Use: Discussion Points Email Facebook Twitter ... was last updated February 2017 Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal ...

  18. Zero Point Energy of Renormalized Wilson Loops

    OpenAIRE

    Hidaka, Yoshimasa; Pisarski, Robert D.

    2009-01-01

    The quark antiquark potential, and its associated zero point energy, can be extracted from lattice measurements of the Wilson loop. We discuss a unique prescription to renormalize the Wilson loop, for which the perturbative contribution to the zero point energy vanishes identically. A zero point energy can arise nonperturbatively, which we illustrate by considering effective string models. The nonperturbative contribution to the zero point energy vanishes in the Nambu model, but is nonzero wh...

  19. Residual analysis for spatial point processes

    DEFF Research Database (Denmark)

    Baddeley, A.; Turner, R.; Møller, Jesper

    We define residuals for point process models fitted to spatial point pattern data, and propose diagnostic plots based on these residuals. The techniques apply to any Gibbs point process model, which may exhibit spatial heterogeneity, interpoint interaction and dependence on spatial covariates. Ou...... or covariate effects. Q-Q plots of the residuals are effective in diagnosing interpoint interaction. Some existing ad hoc statistics of point patterns (quadrat counts, scan statistic, kernel smoothed intensity, Berman's diagnostic) are recovered as special cases....

  20. Influence of the burning point on the dew point in a diesel engine

    Energy Technology Data Exchange (ETDEWEB)

    Teetz, C.

    1982-06-01

    A computation on the influence of the ignition point on the dew point in a cylinder of a diesel engine is presented. The cylinder-pressure diagrams are shown. The results of computation are given. A later ignition point diminishes the area with cylinder wall temperatures below the dew point. The endangering by cylinder wall temperatures below the dew point is illustrated.

  1. Towards extending IFC with point cloud data

    NARCIS (Netherlands)

    Krijnen, T.F.; Beetz, J.; Ochmann, S.; Vock, R.; Wessel, R.

    2015-01-01

    In this paper we suggest an extension to the Industry Foundation Classes model to integrate point cloud datasets. The proposal includes a schema extension to the core model allowing the storage of points either as Cartesian coordinates, points in parametric space of a surface associated with a

  2. Moving window segmentation framework for point clouds

    NARCIS (Netherlands)

    Sithole, G.; Gorte, B.G.H.

    2012-01-01

    As lidar point clouds become larger streamed processing becomes more attractive. This paper presents a framework for the streamed segmentation of point clouds with the intention of segmenting unstructured point clouds in real-time. The framework is composed of two main components. The first

  3. Computing bubble-points of CO

    NARCIS (Netherlands)

    Ramdin, M.; Balaji, S.P.; Vicent Luna, J.M.; Torres-Knoop, A; Chen, Q.; Dubbeldam, D.; Calero, S; de Loos, T.W.; Vlugt, T.J.H.

    2016-01-01

    Computing bubble-points of multicomponent mixtures using Monte Carlo simulations is a non-trivial task. A new method is used to compute gas compositions from a known temperature, bubble-point pressure, and liquid composition. Monte Carlo simulations are used to calculate the bubble-points of

  4. Inhomogeneous Markov point processes by transformation

    DEFF Research Database (Denmark)

    Jensen, Eva B. Vedel; Nielsen, Linda Stougaard

    2000-01-01

    We construct parametrized models for point processes, allowing for both inhomogeneity and interaction. The inhomogeneity is obtained by applying parametrized transformations to homogeneous Markov point processes. An interesting model class, which can be constructed by this transformation approach......, is that of exponential inhomogeneous Markov point processes. Statistical inference For such processes is discussed in some detail....

  5. RELATIONSHIP BETWEEN FLASH POINTS OF SOME BINARY ...

    African Journals Online (AJOL)

    B. S. Chandravanshi

    Miscellaneous binary blends containing solvent neutral-150 (SN-150), ... viscosity, the flash point test has always been a standard part of a lubricant's specification. ... between structure and flash points of organic compounds [5-12] and fuels [13, 14]. ... in binary mixtures, the gaps between flash points would be high enough.

  6. How PowerPoint Is Killing Education

    Science.gov (United States)

    Isseks, Marc

    2011-01-01

    Although it is essential to incorporate new technologies into the classroom, says Isseks, one trend has negatively affected instruction--the misuse of PowerPoint presentations. The author describes how poorly designed PowerPoint presentations reduce complex thoughts to bullet points and reduce the act of learning to transferring text from slide to…

  7. Characterization of finite spaces having dispersion points

    International Nuclear Information System (INIS)

    Al-Bsoul, A. T

    1997-01-01

    In this paper we shall characterize the finite spaces having dispersion points. Also, we prove that the dispersion point of a finite space with a dispersion points fixed under all non constant continuous functions which answers the question raised by J. C obb and W. Voxman in 1980 affirmatively for finite space. Some open problems are given. (author). 16 refs

  8. The Fermat point for a taxicab triangle

    Science.gov (United States)

    Hanson, J. R.

    2015-04-01

    The Fermat point P for a triangle ABC is the point P the sum of whose distances from the vertices A, B and C is a minimum. This note will show how to find the Fermat point for any triangle using the taxicab metric.

  9. 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

  10. 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

  11. Equipartitioning and balancing points of polygons

    Directory of Open Access Journals (Sweden)

    Shunmugam Pillay

    2010-07-01

    Full Text Available The centre of mass G of a triangle has the property that the rays to the vertices from G sweep out triangles having equal areas. We show that such points, termed equipartitioning points in this paper, need not exist in other polygons. A necessary and sufficient condition for a quadrilateral to have an equipartitioning point is that one of its diagonals bisects the other. The general theorem, namely, necessary and sufficient conditions for equipartitioning points for arbitrary polygons to exist, is also stated and proved. When this happens, they are in general, distinct from the centre of mass. In parallelograms, and only in them, do the two points coincide.

  12. Beginning SharePoint Designer 2010

    CERN Document Server

    Windischman, Woodrow W; Rehmani, Asif

    2010-01-01

    Teaching Web designers, developers, and IT professionals how to use the new version of SharePoint Designer. Covering both the design and business applications of SharePoint Designer, this complete Wrox guide brings readers thoroughly up to speed on how to use SharePoint Designer in an enterprise. You'll learn to create and modify web pages, use CSS editing tools to modify themes, use Data View to create interactivity with SharePoint and other data, and much more. Coverage includes integration points with Visual Studio, Visio, and InfoPath.: Shows web designers, developers, and IT professionals

  13. Zero point energy of renormalized Wilson loops

    International Nuclear Information System (INIS)

    Hidaka, Yoshimasa; Pisarski, Robert D.

    2009-01-01

    The quark-antiquark potential, and its associated zero point energy, can be extracted from lattice measurements of the Wilson loop. We discuss a unique prescription to renormalize the Wilson loop, for which the perturbative contribution to the zero point energy vanishes identically. A zero point energy can arise nonperturbatively, which we illustrate by considering effective string models. The nonperturbative contribution to the zero point energy vanishes in the Nambu model, but is nonzero when terms for extrinsic curvature are included. At one loop order, the nonperturbative contribution to the zero point energy is negative, regardless of the sign of the extrinsic curvature term.

  14. 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

  15. X-point effect on edge stability

    International Nuclear Information System (INIS)

    Saarelma, S; Kirk, A; Kwon, O J

    2011-01-01

    We study the effects of the X-point configuration on edge localized mode (ELM) triggering peeling and ballooning modes using fixed boundary equilibria and modifying the plasma shape to approach the limit of a true X-point. The current driven pure peeling modes are asymptotically stabilized by the X-point while the stabilizing effect on ballooning modes depends on the poloidal location of the X-point. The coupled peeling-ballooning modes experience the elimination of the peeling component as the X-point is introduced. This can significantly affect the edge stability diagrams used to analyse the ELM triggering mechanisms.

  16. Critical point analysis of phase envelope diagram

    Energy Technology Data Exchange (ETDEWEB)

    Soetikno, Darmadi; Siagian, Ucok W. R. [Department of Petroleum Engineering, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia); Kusdiantara, Rudy, E-mail: rkusdiantara@s.itb.ac.id; Puspita, Dila, E-mail: rkusdiantara@s.itb.ac.id; Sidarto, Kuntjoro A., E-mail: rkusdiantara@s.itb.ac.id; Soewono, Edy; Gunawan, Agus Y. [Department of Mathematics, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia)

    2014-03-24

    Phase diagram or phase envelope is a relation between temperature and pressure that shows the condition of equilibria between the different phases of chemical compounds, mixture of compounds, and solutions. Phase diagram is an important issue in chemical thermodynamics and hydrocarbon reservoir. It is very useful for process simulation, hydrocarbon reactor design, and petroleum engineering studies. It is constructed from the bubble line, dew line, and critical point. Bubble line and dew line are composed of bubble points and dew points, respectively. Bubble point is the first point at which the gas is formed when a liquid is heated. Meanwhile, dew point is the first point where the liquid is formed when the gas is cooled. Critical point is the point where all of the properties of gases and liquids are equal, such as temperature, pressure, amount of substance, and others. Critical point is very useful in fuel processing and dissolution of certain chemicals. Here in this paper, we will show the critical point analytically. Then, it will be compared with numerical calculations of Peng-Robinson equation by using Newton-Raphson method. As case studies, several hydrocarbon mixtures are simulated using by Matlab.

  17. Critical point analysis of phase envelope diagram

    International Nuclear Information System (INIS)

    Soetikno, Darmadi; Siagian, Ucok W. R.; Kusdiantara, Rudy; Puspita, Dila; Sidarto, Kuntjoro A.; Soewono, Edy; Gunawan, Agus Y.

    2014-01-01

    Phase diagram or phase envelope is a relation between temperature and pressure that shows the condition of equilibria between the different phases of chemical compounds, mixture of compounds, and solutions. Phase diagram is an important issue in chemical thermodynamics and hydrocarbon reservoir. It is very useful for process simulation, hydrocarbon reactor design, and petroleum engineering studies. It is constructed from the bubble line, dew line, and critical point. Bubble line and dew line are composed of bubble points and dew points, respectively. Bubble point is the first point at which the gas is formed when a liquid is heated. Meanwhile, dew point is the first point where the liquid is formed when the gas is cooled. Critical point is the point where all of the properties of gases and liquids are equal, such as temperature, pressure, amount of substance, and others. Critical point is very useful in fuel processing and dissolution of certain chemicals. Here in this paper, we will show the critical point analytically. Then, it will be compared with numerical calculations of Peng-Robinson equation by using Newton-Raphson method. As case studies, several hydrocarbon mixtures are simulated using by Matlab

  18. Handbook of floating-point arithmetic

    CERN Document Server

    Muller, Jean-Michel; de Dinechin, Florent; Jeannerod, Claude-Pierre; Joldes, Mioara; Lefèvre, Vincent; Melquiond, Guillaume; Revol, Nathalie; Torres, Serge

    2018-01-01

    This handbook is a definitive guide to the effective use of modern floating-point arithmetic, which has considerably evolved, from the frequently inconsistent floating-point number systems of early computing to the recent IEEE 754-2008 standard. Most of computational mathematics depends on floating-point numbers, and understanding their various implementations will allow readers to develop programs specifically tailored for the standard’s technical features. Algorithms for floating-point arithmetic are presented throughout the book and illustrated where possible by example programs which show how these techniques appear in actual coding and design. The volume itself breaks its core topic into four parts: the basic concepts and history of floating-point arithmetic; methods of analyzing floating-point algorithms and optimizing them; implementations of IEEE 754-2008 in hardware and software; and useful extensions to the standard floating-point system, such as interval arithmetic, double- and triple-word arithm...

  19. Interval Mathematics Applied to Critical Point Transitions

    Directory of Open Access Journals (Sweden)

    Benito A. Stradi

    2012-03-01

    Full Text Available The determination of critical points of mixtures is important for both practical and theoretical reasons in the modeling of phase behavior, especially at high pressure. The equations that describe the behavior of complex mixtures near critical points are highly nonlinear and with multiplicity of solutions to the critical point equations. Interval arithmetic can be used to reliably locate all the critical points of a given mixture. The method also verifies the nonexistence of a critical point if a mixture of a given composition does not have one. This study uses an interval Newton/Generalized Bisection algorithm that provides a mathematical and computational guarantee that all mixture critical points are located. The technique is illustrated using several example problems. These problems involve cubic equation of state models; however, the technique is general purpose and can be applied in connection with other nonlinear problems.

  20. 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

  1. Describing chaotic attractors: Regular and perpetual points

    Science.gov (United States)

    Dudkowski, Dawid; Prasad, Awadhesh; Kapitaniak, Tomasz

    2018-03-01

    We study the concepts of regular and perpetual points for describing the behavior of chaotic attractors in dynamical systems. The idea of these points, which have been recently introduced to theoretical investigations, is thoroughly discussed and extended into new types of models. We analyze the correlation between regular and perpetual points, as well as their relation with phase space, showing the potential usefulness of both types of points in the qualitative description of co-existing states. The ability of perpetual points in finding attractors is indicated, along with its potential cause. The location of chaotic trajectories and sets of considered points is investigated and the study on the stability of systems is shown. The statistical analysis of the observing desired states is performed. We focus on various types of dynamical systems, i.e., chaotic flows with self-excited and hidden attractors, forced mechanical models, and semiconductor superlattices, exhibiting the universality of appearance of the observed patterns and relations.

  2. Algorithms for solving common fixed point problems

    CERN Document Server

    Zaslavski, Alexander J

    2018-01-01

    This book details approximate solutions to common fixed point problems and convex feasibility problems in the presence of perturbations. Convex feasibility problems search for a common point of a finite collection of subsets in a Hilbert space; common fixed point problems pursue a common fixed point of a finite collection of self-mappings in a Hilbert space. A variety of algorithms are considered in this book for solving both types of problems, the study of which has fueled a rapidly growing area of research. This monograph is timely and highlights the numerous applications to engineering, computed tomography, and radiation therapy planning. Totaling eight chapters, this book begins with an introduction to foundational material and moves on to examine iterative methods in metric spaces. The dynamic string-averaging methods for common fixed point problems in normed space are analyzed in Chapter 3. Dynamic string methods, for common fixed point problems in a metric space are introduced and discussed in Chapter ...

  3. Kantian Turning Point in Gadamer's Philosophical Hermeneutics

    Directory of Open Access Journals (Sweden)

    Kristína Bosáková

    2016-11-01

    Full Text Available The paper is treating the theme of a Kantian turning-point in the philosophical hermeneutics of H.- G. Gadamer based on of the harmonic relationship between metaphysics and science in Kantian philosophy from the point of view of the philosophical hermeneutics of Gadamer. The philosophical work of Kant had such an influence on Gadamer that without exaggerating we can talk about the Kantian turning-point in Gadamerian hermeneutics. Grondin, a former student of Gadamer, is talking about Kantian turning-point on the field of aesthetics, but in reality Kantian turning-point means much more than a mere change in the reception of the concept of judgement. It is a discovery of harmonical relationship between the beauty and the moral, between the reason and the sensitivity, between the modern sciences and the metaphysical tradition in the Kantian philosophy, made by Gadamer. This is what we call the Kantian turning-point in Gadamerian hermeneutics.

  4. Fixed points of occasionally weakly biased mappings

    OpenAIRE

    Y. Mahendra Singh, M. R. Singh

    2012-01-01

    Common fixed point results due to Pant et al. [Pant et al., Weak reciprocal continuity and fixed point theorems, Ann Univ Ferrara, 57(1), 181-190 (2011)] are extended to a class of non commuting operators called occasionally weakly biased pair[ N. Hussain, M. A. Khamsi A. Latif, Commonfixed points for JH-operators and occasionally weakly biased pairs under relaxed conditions, Nonlinear Analysis, 74, 2133-2140 (2011)]. We also provideillustrative examples to justify the improvements. Abstract....

  5. Common fixed points for weakly compatible maps

    Indian Academy of Sciences (India)

    Springer Verlag Heidelberg #4 2048 1996 Dec 15 10:16:45

    In 1976, Jungck [4] proved a common fixed point theorem for commuting maps generalizing the Banach's fixed point theorem, which states that, 'let (X, d) be a complete metric space. If T satisfies d(Tx,Ty) ≤ kd(x,y) for each x,y ∈ X where 0 ≤ k < 1, then T has a unique fixed point in X'. This theorem has many applications, ...

  6. Infra-red fixed points in supersymmetry

    Indian Academy of Sciences (India)

    ¾c /font>, and c stands for the color quadratic Casimir of the field. Fixed points arise when R* ¼ or when R*. /nobr>. ´S-½. µ ´r ·b¿µ. The stability of the solutions may be tested by linearizing the system about the fixed points. For the non-trivial fixed points we need to consider the eigenvalues of the stability matrix whose ...

  7. Bayesian analysis of Markov point processes

    DEFF Research Database (Denmark)

    Berthelsen, Kasper Klitgaard; Møller, Jesper

    2006-01-01

    Recently Møller, Pettitt, Berthelsen and Reeves introduced a new MCMC methodology for drawing samples from a posterior distribution when the likelihood function is only specified up to a normalising constant. We illustrate the method in the setting of Bayesian inference for Markov point processes...... a partially ordered Markov point process as the auxiliary variable. As the method requires simulation from the "unknown" likelihood, perfect simulation algorithms for spatial point processes become useful....

  8. 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

  9. Calculation of melting points of oxides

    International Nuclear Information System (INIS)

    Bobkova, O.S.; Voskobojnikov, V.G.; Kozin, A.I.

    1975-01-01

    The correlation between the melting point and thermodynamic parameters characterizing the strength of oxides and compounds is given. Such thermodynamic paramters include the energy and antropy of atomization

  10. 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

  11. EPA Region 1 Environmentally Sensitive Areas (Points)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This coverage represents point equivalents of environmentally sensitive areas in EPA New England. This coverage represents polygon equivalents of environmentally...

  12. PowerPoint 2007 for Dummies

    CERN Document Server

    Lowe, Doug

    2007-01-01

    New and inexperienced PowerPoint users will discover how to use the latest enhancements to PowerPoint 2007 quickly and efficiently so that they can produce unique and informative presentations PowerPoint continues to be the world's most popular presentation software This updated For Dummies guide shows users different ways to create powerful and effective slideshow presentations that incorporate data from other applications in the form of charts, clip art, sound, and video Shares the key features of PowerPoint 2007 including creating and editing slides, working with hyperlinks and action butt

  13. Blossom Point Satellite Tracking and Command Station

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: The Blossom Point Satellite Command and Tracking Facility (BP) provides engineering and operational support to several complex space systems for the Navy...

  14. Track length estimation applied to point detectors

    International Nuclear Information System (INIS)

    Rief, H.; Dubi, A.; Elperin, T.

    1984-01-01

    The concept of the track length estimator is applied to the uncollided point flux estimator (UCF) leading to a new algorithm of calculating fluxes at a point. It consists essentially of a line integral of the UCF, and although its variance is unbounded, the convergence rate is that of a bounded variance estimator. In certain applications, involving detector points in the vicinity of collimated beam sources, it has a lower variance than the once-more-collided point flux estimator, and its application is more straightforward

  15. 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

  16. Teach yourself visually PowerPoint 2013

    CERN Document Server

    Wood, William

    2013-01-01

    A straightforward, visual approach to learning the new PowerPoint 2013! PowerPoint 2013 boasts updated features and new possibilities; this highly visual tutorial provides step-by-step instructions to help you learn all the capabilities of PowerPoint 2013. It covers the basics, as well as all the exciting new changes and additions in a series of easy-to-follow, full-color, two-page tutorials. Learn how to create slides, dress them up using templates and graphics, add sound and animation, and more. This book is the ideal ""show me, don't tell me"" guide to PowerPoint 2013.De

  17. Wolf Point Substation, Roosevelt County, Montana

    International Nuclear Information System (INIS)

    1991-05-01

    The Western Area Power Administration (Western), an agency of the United States Department of Energy, is proposing to construct the 115-kV Wolf Point Substation near Wolf Point in Roosevelt County, Montana (Figure 1). As part of the construction project, Western's existing Wolf Point Substation would be taken out of service. The existing 115-kV Wolf Point Substation is located approximately 3 miles west of Wolf Point, Montana (Figure 2). The substation was constructed in 1949. The existing Wolf Point Substation serves as a ''Switching Station'' for the 115-kV transmission in the region. The need for substation improvements is based on operational and reliability issues. For this environmental assessment (EA), the environmental review of the proposed project took into account the removal of the old Wolf Point Substation, rerouting of the five Western lines and four lines from the Cooperatives and Montana-Dakota Utilities Company, and the new road into the proposed substation. Reference to the new proposed Wolf Point Substation in the EA includes these facilities as well as the old substation site. The environmental review looked at the impacts to all resource areas in the Wolf Point area. 7 refs., 6 figs

  18. Parametric Architectural Design with Point-clouds

    DEFF Research Database (Denmark)

    Zwierzycki, Mateusz; Evers, Henrik Leander; Tamke, Martin

    2016-01-01

    This paper investigates the efforts and benefits of the implementation of point clouds into architectural design processes and tools. Based on a study on the principal work processes of designers with point clouds the prototypical plugin/library - Volvox - was developed for the parametric modelling...

  19. Point cloud data management (extended abstract)

    NARCIS (Netherlands)

    Van Oosterom, P.J.M.; Ravada, S.; Horhammer, M.; Martinez Rubi, O.; Ivanova, M.; Kodde, M.; Tijssen, T.P.M.

    2014-01-01

    Point cloud data are important sources for 3D geo-information. The point cloud data sets are growing in popularity and in size. Modern Big Data acquisition and processing technologies, such as laser scanning from airborne, mobile, or static platforms, dense image matching from photos, multi-beam

  20. The Psychic Organ Point of Autistic Syntax

    Science.gov (United States)

    Amir, Dana

    2013-01-01

    This paper deals with autistic syntax and its expressions both in the fully fledged autistic structure and in the autistic zones of other personality structures. The musical notion of the organ point serves as a point of departure in an attempt to describe how autistic syntax transforms what was meant to constitute the substrate for linguistic…

  1. Finite Elements on Point Based Surfaces

    NARCIS (Netherlands)

    Clarenz, U.; Rumpf, M.; Telea, A.

    2004-01-01

    We present a framework for processing point-based surfaces via partial differential equations (PDEs). Our framework efficiently and effectively brings well-known PDE-based processing techniques to the field of point-based surfaces. Our method is based on the construction of local tangent planes and

  2. Magnetic Fixed Points and Emergent Supersymmetry

    DEFF Research Database (Denmark)

    Antipin, Oleg; Mojaza, Matin; Pica, Claudio

    2013-01-01

    We establish in perturbation theory the existence of fixed points along the renormalization group flow for QCD with an adjoint Weyl fermion and scalar matter reminiscent of magnetic duals of QCD [1-3]. We classify the fixed points by analyzing their basin of attraction. We discover that among...

  3. The improbability of Harris interest points

    DEFF Research Database (Denmark)

    Loog, Marco; Lauze, Francois Bernard

    2010-01-01

    An elementary characterization of the map underlying Harris corners, also known as Harris interest points or key points, is provided. Two principal and basic assumptions made are: 1) Local image structure is captured in an uncommitted way, simply using weighted raw image values around every image...

  4. Gravitational Zero Point Energy induces Physical Observables

    OpenAIRE

    Garattini, Remo

    2010-01-01

    We consider the contribution of Zero Point Energy on the induced Cosmological Constant and on the induced Electric/Magnetic charge in absence of matter fields. The method is applicable to every spherically symmetric background. Extensions to a generic $f(R) $ theory are also allowed. Only the graviton appears to be fundamental to the determination of Zero Point Energy.

  5. Zero-point energy in spheroidal geometries

    OpenAIRE

    Kitson, A. R.; Signal, A. I.

    2005-01-01

    We study the zero-point energy of a massless scalar field subject to spheroidal boundary conditions. Using the zeta-function method, the zero-point energy is evaluated for small ellipticity. Axially symmetric vector fields are also considered. The results are interpreted within the context of QCD flux tubes and the MIT bag model.

  6. State estimation for temporal point processes

    NARCIS (Netherlands)

    van Lieshout, Maria Nicolette Margaretha

    2015-01-01

    This paper is concerned with combined inference for point processes on the real line observed in a broken interval. For such processes, the classic history-based approach cannot be used. Instead, we adapt tools from sequential spatial point processes. For a range of models, the marginal and

  7. Metallic and antiferromagnetic fixed points from gravity

    Science.gov (United States)

    Paul, Chandrima

    2018-06-01

    We consider SU(2) × U(1) gauge theory coupled to matter field in adjoints and study RG group flow. We constructed Callan-Symanzik equation and subsequent β functions and study the fixed points. We find there are two fixed points, showing metallic and antiferromagnetic behavior. We have shown that metallic phase develops an instability if certain parametric conditions are satisfied.

  8. Developing a Teachable Point of View

    Science.gov (United States)

    Cameron, Kim

    2007-01-01

    As professors of management and organizational behavior mature in their teaching, they should begin to develop a teachable point of view. In this article, the author describes several attributes of a teachable point of view. Based on his own teaching experience, the author outlines five criteria for the content of the material taught--the what of…

  9. The Improbability of Harris Interest Points

    NARCIS (Netherlands)

    Loog, M.; Lauze, F.B.

    2010-01-01

    An elementary characterization of the map underlying Harris corners, also known as Harris interest points or key points, is provided. Two principal and basic assumptions made are: 1) Local image structure is captured in an uncommitted way, simply using weighted raw image values around every image

  10. Impedance analysis of acupuncture points and pathways

    International Nuclear Information System (INIS)

    Teplan, Michal; Kukucka, Marek; Ondrejkovicová, Alena

    2011-01-01

    Investigation of impedance characteristics of acupuncture points from acoustic to radio frequency range is addressed. Discernment and localization of acupuncture points in initial single subject study was unsuccessfully attempted by impedance map technique. Vector impedance analyses determined possible resonant zones in MHz region.

  11. TOPOLOGY OF RANDOM POINTS YOGESHWARAN. D.

    Indian Academy of Sciences (India)

    Balls grow at unit rate centred at the points of the point cloud/ process. ... Idea of persistence : Keep track of births and deaths of topological features. ..... holes, Betti numbers, etc., one will be more interested in the distribution of such objects on ...

  12. Fixed points in a group of isometries

    NARCIS (Netherlands)

    Voorneveld, M.

    2000-01-01

    The Bruhat-Tits xed point theorem states that a group of isometries on a complete metric space with negative curvature possesses a xed point if it has a bounded orbit. This theorem is extended by a relaxation of the negative curvature condition in terms of the w-distance functions introduced by Kada

  13. Determinants of College Grade Point Averages

    Science.gov (United States)

    Bailey, Paul Dean

    2012-01-01

    Chapter 2: The Role of Class Difficulty in College Grade Point Averages. Grade Point Averages (GPAs) are widely used as a measure of college students' ability. Low GPAs can remove a students from eligibility for scholarships, and even continued enrollment at a university. However, GPAs are determined not only by student ability but also by the…

  14. NIM Realization of the Gallium Triple Point

    Science.gov (United States)

    Xiaoke, Yan; Ping, Qiu; Yuning, Duan; Yongmei, Qu

    2003-09-01

    In the last three years (1999 to 2001), the gallium triple-point cell has been successfully developed, and much corresponding research has been carried out at the National Institute of Metrology (NIM), Beijing, China. This paper presents the cell design, apparatus and procedure for realizing the gallium triple point, and presents studies on the different freezing methods. The reproducibility is 0.03 mK, and the expanded uncertainty of realization of the gallium triple point is evaluated to be 0.17 mK (p=0.99, k=2.9). Also, the reproducibility of the gallium triple point was compared with that of the triple point of water.

  15. MODEL FOR SEMANTICALLY RICH POINT CLOUD DATA

    Directory of Open Access Journals (Sweden)

    F. Poux

    2017-10-01

    Full Text Available This paper proposes an interoperable model for managing high dimensional point clouds while integrating semantics. Point clouds from sensors are a direct source of information physically describing a 3D state of the recorded environment. As such, they are an exhaustive representation of the real world at every scale: 3D reality-based spatial data. Their generation is increasingly fast but processing routines and data models lack of knowledge to reason from information extraction rather than interpretation. The enhanced smart point cloud developed model allows to bring intelligence to point clouds via 3 connected meta-models while linking available knowledge and classification procedures that permits semantic injection. Interoperability drives the model adaptation to potentially many applications through specialized domain ontologies. A first prototype is implemented in Python and PostgreSQL database and allows to combine semantic and spatial concepts for basic hybrid queries on different point clouds.

  16. Model for Semantically Rich Point Cloud Data

    Science.gov (United States)

    Poux, F.; Neuville, R.; Hallot, P.; Billen, R.

    2017-10-01

    This paper proposes an interoperable model for managing high dimensional point clouds while integrating semantics. Point clouds from sensors are a direct source of information physically describing a 3D state of the recorded environment. As such, they are an exhaustive representation of the real world at every scale: 3D reality-based spatial data. Their generation is increasingly fast but processing routines and data models lack of knowledge to reason from information extraction rather than interpretation. The enhanced smart point cloud developed model allows to bring intelligence to point clouds via 3 connected meta-models while linking available knowledge and classification procedures that permits semantic injection. Interoperability drives the model adaptation to potentially many applications through specialized domain ontologies. A first prototype is implemented in Python and PostgreSQL database and allows to combine semantic and spatial concepts for basic hybrid queries on different point clouds.

  17. Thinning spatial point processes into Poisson processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Schoenberg, Frederic Paik

    2010-01-01

    are identified, and where we simulate backwards and forwards in order to obtain the thinned process. In the case of a Cox process, a simple independent thinning technique is proposed. In both cases, the thinning results in a Poisson process if and only if the true Papangelou conditional intensity is used, and......In this paper we describe methods for randomly thinning certain classes of spatial point processes. In the case of a Markov point process, the proposed method involves a dependent thinning of a spatial birth-and-death process, where clans of ancestors associated with the original points......, thus, can be used as a graphical exploratory tool for inspecting the goodness-of-fit of a spatial point process model. Several examples, including clustered and inhibitive point processes, are considered....

  18. Thinning spatial point processes into Poisson processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Schoenberg, Frederic Paik

    , and where one simulates backwards and forwards in order to obtain the thinned process. In the case of a Cox process, a simple independent thinning technique is proposed. In both cases, the thinning results in a Poisson process if and only if the true Papangelou conditional intensity is used, and thus can......This paper describes methods for randomly thinning certain classes of spatial point processes. In the case of a Markov point process, the proposed method involves a dependent thinning of a spatial birth-and-death process, where clans of ancestors associated with the original points are identified...... be used as a diagnostic for assessing the goodness-of-fit of a spatial point process model. Several examples, including clustered and inhibitive point processes, are considered....

  19. 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

  20. 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

  1. 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

  2. The power of PowerPoint.

    Science.gov (United States)

    Niamtu , J

    2001-08-01

    Carousel slide presentations have been used for academic and clinical presentations since the late 1950s. However, advances in computer technology have caused a paradigm shift, and digital presentations are quickly becoming standard for clinical presentations. The advantages of digital presentations include cost savings; portability; easy updating capability; Internet access; multimedia functions, such as animation, pictures, video, and sound; and customization to augment audience interest and attention. Microsoft PowerPoint has emerged as the most popular digital presentation software and is currently used by many practitioners with and without significant computer expertise. The user-friendly platform of PowerPoint enables even the novice presenter to incorporate digital presentations into his or her profession. PowerPoint offers many advanced options that, with a minimal investment of time, can be used to create more interactive and professional presentations for lectures, patient education, and marketing. Examples of advanced PowerPoint applications are presented in a stepwise manner to unveil the full power of PowerPoint. By incorporating these techniques, medical practitioners can easily personalize, customize, and enhance their PowerPoint presentations. Complications, pitfalls, and caveats are discussed to detour and prevent misadventures in digital presentations. Relevant Web sites are listed to further update, customize, and communicate PowerPoint techniques.

  3. Detecting Change-Point via Saddlepoint Approximations

    Institute of Scientific and Technical Information of China (English)

    Zhaoyuan LI; Maozai TIAN

    2017-01-01

    It's well-known that change-point problem is an important part of model statistical analysis.Most of the existing methods are not robust to criteria of the evaluation of change-point problem.In this article,we consider "mean-shift" problem in change-point studies.A quantile test of single quantile is proposed based on saddlepoint approximation method.In order to utilize the information at different quantile of the sequence,we further construct a "composite quantile test" to calculate the probability of every location of the sequence to be a change-point.The location of change-point can be pinpointed rather than estimated within a interval.The proposed tests make no assumptions about the functional forms of the sequence distribution and work sensitively on both large and small size samples,the case of change-point in the tails,and multiple change-points situation.The good performances of the tests are confirmed by simulations and real data analysis.The saddlepoint approximation based distribution of the test statistic that is developed in the paper is of independent interest and appealing.This finding may be of independent interest to the readers in this research area.

  4. Interest point detection for hyperspectral imagery

    Science.gov (United States)

    Dorado-Muñoz, Leidy P.; Vélez-Reyes, Miguel; Roysam, Badrinath; Mukherjee, Amit

    2009-05-01

    This paper presents an algorithm for automated extraction of interest points (IPs)in multispectral and hyperspectral images. Interest points are features of the image that capture information from its neighbours and they are distinctive and stable under transformations such as translation and rotation. Interest-point operators for monochromatic images were proposed more than a decade ago and have since been studied extensively. IPs have been applied to diverse problems in computer vision, including image matching, recognition, registration, 3D reconstruction, change detection, and content-based image retrieval. Interest points are helpful in data reduction, and reduce the computational burden of various algorithms (like registration, object detection, 3D reconstruction etc) by replacing an exhaustive search over the entire image domain by a probe into a concise set of highly informative points. An interest operator seeks out points in an image that are structurally distinct, invariant to imaging conditions, stable under geometric transformation, and interpretable which are good candidates for interest points. Our approach extends ideas from Lowe's keypoint operator that uses local extrema of Difference of Gaussian (DoG) operator at multiple scales to detect interest point in gray level images. The proposed approach extends Lowe's method by direct conversion of scalar operations such as scale-space generation, and extreme point detection into operations that take the vector nature of the image into consideration. Experimental results with RGB and hyperspectral images which demonstrate the potential of the method for this application and the potential improvements of a fully vectorial approach over band-by-band approaches described in the literature.

  5. Point Information Gain and Multidimensional Data Analysis

    Directory of Open Access Journals (Sweden)

    Renata Rychtáriková

    2016-10-01

    Full Text Available We generalize the point information gain (PIG and derived quantities, i.e., point information gain entropy (PIE and point information gain entropy density (PIED, for the case of the Rényi entropy and simulate the behavior of PIG for typical distributions. We also use these methods for the analysis of multidimensional datasets. We demonstrate the main properties of PIE/PIED spectra for the real data with the examples of several images and discuss further possible utilizations in other fields of data processing.

  6. Dynamics and mission design near libration points

    CERN Document Server

    Gómez, G; Llibre, J; Martínez, R

    2001-01-01

    It is well known that the restricted three-body problem has triangular equilibrium points. These points are linearly stable for values of the mass parameter, µ , below Routh's critical value, µ 1 . It is also known that in the spatial case they are nonlinearly stable, not for all the initial conditions in a neighborhood of the equilibrium points L 4 , L 5 but for a set of relatively large measures. This follows from the celebrated Kolmogorov-Arnold-Moser theorem. In fact there are neighborhoods of computable size for which one obtains "practical stability" in the sense that the massless partic

  7. PowerPoint 2013 for dummies

    CERN Document Server

    Lowe, Doug

    2013-01-01

    Get up and running with this full-color guide to PowerPoint 2013! PowerPoint, the number one presentation software, has been revised and improved with the introduction of Microsoft Office 2013. With this all-new, full-color book by your side, you will learn how to take full advantage of all of PowerPoint's powerful and dynamic capabilities. Bestselling veteran For Dummies, author Doug Lowe breaks it all down so that you can create a powerful and effective slideshow presentation with the new wide-screen theme and variant that incorporates videos, pictures, and shapes, and all

  8. The Antitriangular Factorization of Saddle Point Matrices

    KAUST Repository

    Pestana, J.

    2014-01-01

    Mastronardi and Van Dooren [SIAM J. Matrix Anal. Appl., 34 (2013), pp. 173-196] recently introduced the block antitriangular ("Batman") decomposition for symmetric indefinite matrices. Here we show the simplification of this factorization for saddle point matrices and demonstrate how it represents the common nullspace method. We show that rank-1 updates to the saddle point matrix can be easily incorporated into the factorization and give bounds on the eigenvalues of matrices important in saddle point theory. We show the relation of this factorization to constraint preconditioning and how it transforms but preserves the structure of block diagonal and block triangular preconditioners. © 2014 Society for Industrial and Applied Mathematics.

  9. The universal cardinal ordering of fixed points

    International Nuclear Information System (INIS)

    San Martin, Jesus; Moscoso, Ma Jose; Gonzalez Gomez, A.

    2009-01-01

    We present the theorem which determines, by a permutation, the cardinal ordering of fixed points for any orbit of a period doubling cascade. The inverse permutation generates the orbit and the symbolic sequence of the orbit is obtained as a corollary. Interestingly enough, it is important to point that this theorem needs no previous information about any other orbit; also the cardinal ordering is achieved automatically with no need to compare numerical values associated with every point of the orbit (as would be the case if kneading theory were used).

  10. About Applications of the Fixed Point Theory

    Directory of Open Access Journals (Sweden)

    Bucur Amelia

    2017-06-01

    Full Text Available The fixed point theory is essential to various theoretical and applied fields, such as variational and linear inequalities, the approximation theory, nonlinear analysis, integral and differential equations and inclusions, the dynamic systems theory, mathematics of fractals, mathematical economics (game theory, equilibrium problems, and optimisation problems and mathematical modelling. This paper presents a few benchmarks regarding the applications of the fixed point theory. This paper also debates if the results of the fixed point theory can be applied to the mathematical modelling of quality.

  11. Hybrid fixed point in CAT(0 spaces

    Directory of Open Access Journals (Sweden)

    Hemant Kumar Pathak

    2018-02-01

    Full Text Available In this paper, we introduce an ultrapower approach to prove fixed point theorems for $H^{+}$-nonexpansive multi-valued mappings in the setting of CAT(0 spaces and prove several hybrid fixed point results in CAT(0 spaces for families of single-valued nonexpansive or quasinonexpansive mappings and multi-valued upper semicontinuous, almost lower semicontinuous or $H^{+}$-nonexpansive mappings which are weakly commuting. We also establish a result about structure of the set of fixed points of $H^{+}$-quasinonexpansive mapping on a CAT(0 space.

  12. 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

  13. Quantum entanglement and fixed-point bifurcations

    International Nuclear Information System (INIS)

    Hines, Andrew P.; McKenzie, Ross H.; Milburn, G.J.

    2005-01-01

    How does the classical phase-space structure for a composite system relate to the entanglement characteristics of the corresponding quantum system? We demonstrate how the entanglement in nonlinear bipartite systems can be associated with a fixed-point bifurcation in the classical dynamics. Using the example of coupled giant spins we show that when a fixed point undergoes a supercritical pitchfork bifurcation, the corresponding quantum state--the ground state--achieves its maximum amount of entanglement near the critical point. We conjecture that this will be a generic feature of systems whose classical limit exhibits such a bifurcation

  14. Lévy based Cox point processes

    DEFF Research Database (Denmark)

    Hellmund, Gunnar; Prokesová, Michaela; Jensen, Eva Bjørn Vedel

    2008-01-01

    In this paper we introduce Lévy-driven Cox point processes (LCPs) as Cox point processes with driving intensity function Λ defined by a kernel smoothing of a Lévy basis (an independently scattered, infinitely divisible random measure). We also consider log Lévy-driven Cox point processes (LLCPs......) with Λ equal to the exponential of such a kernel smoothing. Special cases are shot noise Cox processes, log Gaussian Cox processes, and log shot noise Cox processes. We study the theoretical properties of Lévy-based Cox processes, including moment properties described by nth-order product densities...

  15. Power point 2002 for successful presentation

    International Nuclear Information System (INIS)

    Moon, Insoo

    2002-01-01

    This book mentions power point 2002 for successful presentation, which deals with power point and presentation, all guide, the latest gear, for presentation, basic of power point 2002 such as slide, text compile, insertion of picture, figure and application of office guide, setting up new year plan using text like insertion text with various methods, compile effective text, and 200% application of tab, and addiction of pretty shape of characters, finishing of conversion of chinese character, and elimination of typographical error with spell checker.

  16. Fixed point theorems in spaces and -trees

    Directory of Open Access Journals (Sweden)

    Kirk WA

    2004-01-01

    Full Text Available We show that if is a bounded open set in a complete space , and if is nonexpansive, then always has a fixed point if there exists such that for all . It is also shown that if is a geodesically bounded closed convex subset of a complete -tree with , and if is a continuous mapping for which for some and all , then has a fixed point. It is also noted that a geodesically bounded complete -tree has the fixed point property for continuous mappings. These latter results are used to obtain variants of the classical fixed edge theorem in graph theory.

  17. Point-of-Purchase Advertising. Learning Activity.

    Science.gov (United States)

    Shackelford, Ray

    1998-01-01

    In this technology education activity, students learn the importance of advertising, conduct a day-long survey of advertising strategies, and design and produce a tabletop point-of-purchase advertisement. (JOW)

  18. Columbia River ESI: NESTS (Nest Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains sensitive biological resource data for bird nesting sites in the Columbia River area. Vector points in this data set represent locations of...

  19. Detecting change-points in extremes

    KAUST Repository

    Dupuis, D. J.

    2015-01-01

    Even though most work on change-point estimation focuses on changes in the mean, changes in the variance or in the tail distribution can lead to more extreme events. In this paper, we develop a new method of detecting and estimating the change-points in the tail of multiple time series data. In addition, we adapt existing tail change-point detection methods to our specific problem and conduct a thorough comparison of different methods in terms of performance on the estimation of change-points and computational time. We also examine three locations on the U.S. northeast coast and demonstrate that the methods are useful for identifying changes in seasonally extreme warm temperatures.

  20. Exact Identification of a Quantum Change Point

    Science.gov (United States)

    Sentís, Gael; Calsamiglia, John; Muñoz-Tapia, Ramon

    2017-10-01

    The detection of change points is a pivotal task in statistical analysis. In the quantum realm, it is a new primitive where one aims at identifying the point where a source that supposedly prepares a sequence of particles in identical quantum states starts preparing a mutated one. We obtain the optimal procedure to identify the change point with certainty—naturally at the price of having a certain probability of getting an inconclusive answer. We obtain the analytical form of the optimal probability of successful identification for any length of the particle sequence. We show that the conditional success probabilities of identifying each possible change point show an unexpected oscillatory behavior. We also discuss local (online) protocols and compare them with the optimal procedure.

  1. Airports and Airfields - Volusia County Airports (Points)

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — The Public Use Airports database is a geographic point database of aircraft landing facilities in the United States and U.S. Territories. This database has been...

  2. Inventory classification based on decoupling points

    Directory of Open Access Journals (Sweden)

    Joakim Wikner

    2015-01-01

    Full Text Available The ideal state of continuous one-piece flow may never be achieved. Still the logistics manager can improve the flow by carefully positioning inventory to buffer against variations. Strategies such as lean, postponement, mass customization, and outsourcing all rely on strategic positioning of decoupling points to separate forecast-driven from customer-order-driven flows. Planning and scheduling of the flow are also based on classification of decoupling points as master scheduled or not. A comprehensive classification scheme for these types of decoupling points is introduced. The approach rests on identification of flows as being either demand based or supply based. The demand or supply is then combined with exogenous factors, classified as independent, or endogenous factors, classified as dependent. As a result, eight types of strategic as well as tactical decoupling points are identified resulting in a process-based framework for inventory classification that can be used for flow design.

  3. The existence of trajectories joining critical points

    International Nuclear Information System (INIS)

    Yu Shuxiang.

    1985-01-01

    In this paper, using the notion of an isolating block and the concept of canonical regions, three existence criteria of trajectories connecting a pair of critical points of planar differential equations are given. (author)

  4. Neutrosophic Crisp Points & Neutrosophic Crisp Ideals

    Directory of Open Access Journals (Sweden)

    A. A. Salama

    2013-03-01

    Full Text Available The purpose of this paper is to define the so called "neutrosophic crisp points" and "neutrosophic crisp ideals", and obtain their fundamental properties. Possible application to GIS topology rules are touched upon.

  5. Water Sample Points, Navajo Nation, 2000, USACE

    Data.gov (United States)

    U.S. Environmental Protection Agency — This point shapefile presents the locations and results for water samples collected on the Navajo Nation by the US Army Corps of Engineers (USACE) for the US...

  6. Point-to-point people with purpose—Exploring the possibility of a commercial traveler market for point-to-point suborbital space transportation

    Science.gov (United States)

    Webber, Derek

    2013-12-01

    An argument was made at the First Arcachon Conference on Private Human Access to Space in 2008 [1] that some systematic market research should be conducted into potential market segments for point-to-point suborbital space transportation (PtP), in order to understand whether a commercial market exists which might augment possible government use for such a vehicle. The cargo market potential was subsequently addressed via desk research, and the results, which resulted in a pessimistic business case outlook, were presented in [2]. The same desk research approach is now used in this paper to address the potential business and wealthy individual passenger traveler market segment ("point-to-point people with purpose"). The results, with the assumed ticket pricing, are not encouraging.

  7. Fixed-Point Configurable Hardware Components

    Directory of Open Access Journals (Sweden)

    Rocher Romuald

    2006-01-01

    Full Text Available To reduce the gap between the VLSI technology capability and the designer productivity, design reuse based on IP (intellectual properties is commonly used. In terms of arithmetic accuracy, the generated architecture can generally only be configured through the input and output word lengths. In this paper, a new kind of method to optimize fixed-point arithmetic IP has been proposed. The architecture cost is minimized under accuracy constraints defined by the user. Our approach allows exploring the fixed-point search space and the algorithm-level search space to select the optimized structure and fixed-point specification. To significantly reduce the optimization and design times, analytical models are used for the fixed-point optimization process.

  8. On Recall Rate of Interest Point Detectors

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Dahl, Anders Lindbjerg; Pedersen, Kim Steenstrup

    2010-01-01

    in relation to the number of interest points, the recall rate as a function of camera position and light variation, and the sensitivity relative to model parameter change. The overall conclusion is that the Harris corner detector has a very high recall rate, but is sensitive to change in scale. The Hessian......In this paper we provide a method for evaluating interest point detectors independently of image descriptors. This is possible because we have compiled a unique data set enabling us to determine if common interest points are found. The data contains 60 scenes of a wide range of object types......, and for each scene we have 119 precisely located camera positions obtained from a camera mounted on an industrial robot arm. The scene surfaces have been scanned using structured light, providing precise 3D ground truth. We have investigated a number of the most popular interest point detectors. This is done...

  9. Poisson point processes imaging, tracking, and sensing

    CERN Document Server

    Streit, Roy L

    2010-01-01

    This overview of non-homogeneous and multidimensional Poisson point processes and their applications features mathematical tools and applications from emission- and transmission-computed tomography to multiple target tracking and distributed sensor detection.

  10. [Sociological aspects of health service access points].

    Science.gov (United States)

    Lecarpentier, Mariana

    The work of health service access points highlights the process of exclusion through marginalisation, the phenomenon of precarity and anthropological tensions between hospitality and inhospitality or between the desirable and undesirable. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Statistical aspects of determinantal point processes

    DEFF Research Database (Denmark)

    Lavancier, Frédéric; Møller, Jesper; Rubak, Ege

    The statistical aspects of determinantal point processes (DPPs) seem largely unexplored. We review the appealing properties of DDPs, demonstrate that they are useful models for repulsiveness, detail a simulation procedure, and provide freely available software for simulation and statistical infer...

  12. Anderson Acceleration for Fixed-Point Iterations

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Homer F. [Worcester Polytechnic Institute, MA (United States)

    2015-08-31

    The purpose of this grant was to support research on acceleration methods for fixed-point iterations, with applications to computational frameworks and simulation problems that are of interest to DOE.

  13. VT E911 ESITE geocoder - address points

    Data.gov (United States)

    Vermont Center for Geographic Information — VT E911 ESITE geocoder - address points. VCGI, in collaboration with the VT E911 Board, has created a suite of geocoding services that can be used to batch geocode...

  14. Southeast Alaska ESI: FISHPT (Fish Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains biological resource data for anadromous fish streams in Southeast Alaska. Vector points in this data set represent locations of fish streams....

  15. Hudson River Sub-Bottom Profile Points

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hudson River Estuary Shallow Water Surveys. Subbottom Profile Points. Subbottom data was collected November 5 to December 15, 2009, in the estuary north from...

  16. VT US EPA Regulated Facilities Point Locations

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The EnvironPollution_ENVPTS2001 data layer is based on the U.S. EPA's Envirofacts point shapefile. The data was provided to VCGI by the Vermont...

  17. Louisiana ESI: SOCECON (Socioeconomic Resource Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains human-use resource data for airport, heliport, marina, and boat ramp locations in Louisiana. Vector points in this data set represent the...

  18. North Slope, Alaska ESI: FACILITY (Facility Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains data for oil field facilities for the North Slope of Alaska. Vector points in this data set represent oil field facility locations. This data...

  19. Pressure Points: Preventing and Controlling Hypertension

    Science.gov (United States)

    ... Issue Past Issues Pressure Points: Preventing and Controlling Hypertension Past Issues / Summer 2006 Table of Contents For ... diagnosed with high blood pressure." Aditional Information On Hypertension MedlinePlus: High blood pressure: http://www.nlm.nih. ...

  20. Southeast Alaska ESI: NESTS (Nest Points)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains biological resource data for alcids, shorebirds, waterfowl, diving birds, pelagic birds, gulls, and terns in Southeast Alaska. Points in this...

  1. Topological fixed point theory of multivalued mappings

    CERN Document Server

    Górniewicz, Lech

    1999-01-01

    This volume presents a broad introduction to the topological fixed point theory of multivalued (set-valued) mappings, treating both classical concepts as well as modern techniques. A variety of up-to-date results is described within a unified framework. Topics covered include the basic theory of set-valued mappings with both convex and nonconvex values, approximation and homological methods in the fixed point theory together with a thorough discussion of various index theories for mappings with a topologically complex structure of values, applications to many fields of mathematics, mathematical economics and related subjects, and the fixed point approach to the theory of ordinary differential inclusions. The work emphasises the topological aspect of the theory, and gives special attention to the Lefschetz and Nielsen fixed point theory for acyclic valued mappings with diverse compactness assumptions via graph approximation and the homological approach. Audience: This work will be of interest to researchers an...

  2. Diffuse scattering from crystals with point defects

    International Nuclear Information System (INIS)

    Andrushevsky, N.M.; Shchedrin, B.M.; Simonov, V.I.; Malakhova, L.F.

    2002-01-01

    The analytical expressions for calculating the intensities of X-ray diffuse scattering from a crystal of finite dimensions and monatomic substitutional, interstitial, or vacancy-type point defects have been derived. The method for the determination of the three-dimensional structure by experimental diffuse-scattering data from crystals with point defects having various concentrations is discussed and corresponding numerical algorithms are suggested

  3. New generation of gas infrared point heaters

    Energy Technology Data Exchange (ETDEWEB)

    Schink, Damian [Pintsch Aben B.V., Dinslaken (Germany)

    2011-11-15

    It is more than thirty years since gas infrared heating for points was introduced on the railway network of what is now Deutsche Bahn. These installations have remained in service right through to the present, with virtually no modifications. More stringent requirements as regards availability, maintainability and remote monitoring have, however, led to the development of a new system of gas infrared heating for points - truly a new generation. (orig.)

  4. Matching fields and lattice points of simplices

    OpenAIRE

    Loho, Georg; Smith, Ben

    2018-01-01

    We show that the Chow covectors of a linkage matching field define a bijection of lattice points and we demonstrate how one can recover the linkage matching field from this bijection. This resolves two open questions from Sturmfels & Zelevinsky (1993) on linkage matching fields. For this, we give an explicit construction that associates a bipartite incidence graph of an ordered partition of a common set to all lattice points in a dilated simplex. Given a triangulation of a product of two simp...

  5. Γ-source Neutral Point Clamped Inverter

    DEFF Research Database (Denmark)

    Mo, Wei; Loh, Poh Chiang; Blaabjerg, Frede

    Transformer based Z-source inverters are recently proposed to achieve promising buck-boost capability. They have improved higher buck-boost capability, smaller size and less components count over Z-source inverters. On the other hand, neutral point clamped inverters have less switching stress...... and better output performance comparing with traditional two-level inverters. Integrating these two types of configurations can help neutral point inverters achieve enhanced votlage buck-boost capability....

  6. Characterizations of fixed points of quantum operations

    International Nuclear Information System (INIS)

    Li Yuan

    2011-01-01

    Let φ A be a general quantum operation. An operator B is said to be a fixed point of φ A , if φ A (B)=B. In this note, we shall show conditions under which B, a fixed point φ A , implies that B is compatible with the operation element of φ A . In particular, we offer an extension of the generalized Lueders theorem.

  7. SIFT based algorithm for point feature tracking

    Directory of Open Access Journals (Sweden)

    Adrian BURLACU

    2007-12-01

    Full Text Available In this paper a tracking algorithm for SIFT features in image sequences is developed. For each point feature extracted using SIFT algorithm a descriptor is computed using information from its neighborhood. Using an algorithm based on minimizing the distance between two descriptors tracking point features throughout image sequences is engaged. Experimental results, obtained from image sequences that capture scaling of different geometrical type object, reveal the performances of the tracking algorithm.

  8. I See Your Point: Infants under 12 Months Understand that Pointing Is Communicative

    Science.gov (United States)

    Krehm, Madelaine; Onishi, Kristine H.; Vouloumanos, Athena

    2014-01-01

    Do young infants understand that pointing gestures allow the pointer to change the information state of a recipient? We used a third-party experimental scenario to examine whether 9- and 11-month-olds understand that a pointer's pointing gesture can inform a recipient about a target object. When the pointer pointed to a target, infants…

  9. A three-point Taylor algorithm for three-point boundary value problems

    NARCIS (Netherlands)

    J.L. López; E. Pérez Sinusía; N.M. Temme (Nico)

    2011-01-01

    textabstractWe consider second-order linear differential equations $\\varphi(x)y''+f(x)y'+g(x)y=h(x)$ in the interval $(-1,1)$ with Dirichlet, Neumann or mixed Dirichlet-Neumann boundary conditions given at three points of the interval: the two extreme points $x=\\pm 1$ and an interior point

  10. Pseudo-dynamic source modelling with 1-point and 2-point statistics of earthquake source parameters

    KAUST Repository

    Song, S. G.; Dalguer, L. A.; Mai, Paul Martin

    2013-01-01

    statistical framework that governs the finite-fault rupture process with 1-point and 2-point statistics of source parameters in order to quantify the variability of finite source models for future scenario events. We test this method by extracting 1-point

  11. Point of sale tobacco advertisements in India.

    Science.gov (United States)

    Chaudhry, S; Chaudhry, S; Chaudhry, K

    2007-01-01

    The effect of any legislation depends on its implementation. Limited studies indicate that tobacco companies may tend to use such provision for surrogate advertising. The point of sale advertisement provision has been placed in the Indian Tobacco Control legislation. The study was undertaken to assess the Indian scenario in this regard. To assess if there are any violations related to provision of point of tobacco sale advertisements under India's comprehensive tobacco Control legislation in different parts of India. Boards over various shops showing advertisements of tobacco products were observed in the cities of Delhi, Mumbai, Kolkata, Trivandrum and Jaipur, between September 2005 and March 2006. The point of sale advertisements mushroomed after the implementation of 2004 tobacco control legislation. Tobacco advertisement boards fully satisfying the point of sale provision were practically non-existent. The most common violation of point of sale advertisements was the larger size of the board but with tobacco advertisement equal to the size indicated in the legislation and remaining area often showing a picture. Invariably two boards were placed together to provide the impression of a large single repetitive advertisement. More than two boards was not common. Tobacco advertisement boards were also observed on closed shops/ warehouses, shops not selling tobacco products and on several adjacent shops. The purpose of the point of sale advertisements seems to be surrogate advertisement of tobacco products, mainly cigarettes.

  12. The Tipping Points of Technology Development

    Directory of Open Access Journals (Sweden)

    Tauno Kekäle

    2014-07-01

    Full Text Available The tipping point, the decisive point in time in the competition between old and new, is an interesting phenomenon in physics of today. This aspect in technology acceptance is connected to many business decisions such as technology investments, product releases, resource allocation, sales forecasts and, ultimately, affects the profitability and even survival of a company. The tipping point itself is based on many stochastic and dynamic variables, and the process may at least partly be described as path-dependent. This paper analyses the tipping point from three aspects: (1 product performance, (2 features of the market and infrastructure (including related technologies and human network externalities, and (3 actions of the incumbents (including customer lock-in, systems lock-in, and sustaining innovation. The paper is based on the Bass s-curve idea and the technology trajectory concept proposed by Dosi. Three illustrative cases are presented to make the point of the multiple factors affecting technology acceptance and, thus, the tipping point. The paper also suggests outlines for further research in field of computer simulation.

  13. Modeling fixation locations using spatial point processes.

    Science.gov (United States)

    Barthelmé, Simon; Trukenbrod, Hans; Engbert, Ralf; Wichmann, Felix

    2013-10-01

    Whenever eye movements are measured, a central part of the analysis has to do with where subjects fixate and why they fixated where they fixated. To a first approximation, a set of fixations can be viewed as a set of points in space; this implies that fixations are spatial data and that the analysis of fixation locations can be beneficially thought of as a spatial statistics problem. We argue that thinking of fixation locations as arising from point processes is a very fruitful framework for eye-movement data, helping turn qualitative questions into quantitative ones. We provide a tutorial introduction to some of the main ideas of the field of spatial statistics, focusing especially on spatial Poisson processes. We show how point processes help relate image properties to fixation locations. In particular we show how point processes naturally express the idea that image features' predictability for fixations may vary from one image to another. We review other methods of analysis used in the literature, show how they relate to point process theory, and argue that thinking in terms of point processes substantially extends the range of analyses that can be performed and clarify their interpretation.

  14. Fermion-induced quantum critical points.

    Science.gov (United States)

    Li, Zi-Xiang; Jiang, Yi-Fan; Jian, Shao-Kai; Yao, Hong

    2017-08-22

    A unified theory of quantum critical points beyond the conventional Landau-Ginzburg-Wilson paradigm remains unknown. According to Landau cubic criterion, phase transitions should be first-order when cubic terms of order parameters are allowed by symmetry in the Landau-Ginzburg free energy. Here, from renormalization group analysis, we show that second-order quantum phase transitions can occur at such putatively first-order transitions in interacting two-dimensional Dirac semimetals. As such type of Landau-forbidden quantum critical points are induced by gapless fermions, we call them fermion-induced quantum critical points. We further introduce a microscopic model of SU(N) fermions on the honeycomb lattice featuring a transition between Dirac semimetals and Kekule valence bond solids. Remarkably, our large-scale sign-problem-free Majorana quantum Monte Carlo simulations show convincing evidences of a fermion-induced quantum critical points for N = 2, 3, 4, 5 and 6, consistent with the renormalization group analysis. We finally discuss possible experimental realizations of the fermion-induced quantum critical points in graphene and graphene-like materials.Quantum phase transitions are governed by Landau-Ginzburg theory and the exceptions are rare. Here, Li et al. propose a type of Landau-forbidden quantum critical points induced by gapless fermions in two-dimensional Dirac semimetals.

  15. Finding a single point of truth

    Energy Technology Data Exchange (ETDEWEB)

    Sokolov, S.; Thijssen, H. [Autodesk Inc, Toronto, ON (Canada); Laslo, D.; Martin, J. [Autodesk Inc., San Rafael, CA (United States)

    2010-07-01

    Electric utilities collect large volumes of data at every level of their business, including SCADA, Smart Metering and Smart Grid initiatives, LIDAR and other 3D imagery surveys. Different types of database systems are used to store the information, rendering data flow within the utility business process extremely complicated. The industry trend has been to endure redundancy of data input and maintenance of multiple copies of the same data across different solution data sets. Efforts have been made to improve the situation with point to point interfaces, but with the tools and solutions available today, a single point of truth can be achieved. Consolidated and validated data can be published into a data warehouse at the right point in the process, making the information available to all other enterprise systems and solutions. This paper explained how the single point of truth spatial data warehouse and process automation services can be configured to streamline the flow of data within the utility business process using the initiate-plan-execute-close (IPEC) utility workflow model. The paper first discussed geospatial challenges faced by utilities and then presented the approach and technology aspects. It was concluded that adoption of systems and solutions that can function with and be controlled by the IPEC workflow can provide significant improvement for utility operations, particularly if those systems are coupled with the spatial data warehouse that reflects a single point of truth. 6 refs., 3 figs.

  16. Variational estimates of point-kinetics parameters

    International Nuclear Information System (INIS)

    Favorite, J.A.; Stacey, W.M. Jr.

    1995-01-01

    Variational estimates of the effect of flux shifts on the integral reactivity parameter of the point-kinetics equations and on regional power fractions were calculated for a variety of localized perturbations in two light water reactor (LWR) model problems representing a small, tightly coupled core and a large, loosely coupled core. For the small core, the flux shifts resulting from even relatively large localized reactivity changes (∼600 pcm) were small, and the standard point-kinetics approximation estimates of reactivity were in error by only ∼10% or less, while the variational estimates were accurate to within ∼1%. For the larger core, significant (>50%) flux shifts occurred in response to local perturbations, leading to errors of the same magnitude in the standard point-kinetics approximation of the reactivity worth. For positive reactivity, the error in the variational estimate of reactivity was only a few percent in the larger core, and the resulting transient power prediction was 1 to 2 orders of magnitude more accurate than with the standard point-kinetics approximation. For a large, local negative reactivity insertion resulting in a large flux shift, the accuracy of the variational estimate broke down. The variational estimate of the effect of flux shifts on reactivity in point-kinetics calculations of transients in LWR cores was found to generally result in greatly improved accuracy, relative to the standard point-kinetics approximation, the exception being for large negative reactivity insertions with large flux shifts in large, loosely coupled cores

  17. Magnonic triply-degenerate nodal points

    Science.gov (United States)

    Owerre, S. A.

    2017-12-01

    We generalize the concept of triply-degenerate nodal points to non-collinear antiferromagnets. Here, we introduce this concept to insulating quantum antiferromagnets on the decorated honeycomb lattice, with spin-1 bosonic quasiparticle excitations known as magnons. We demonstrate the existence of magnonic surface states with constant energy contours that form pairs of magnonic arcs connecting the surface projection of the magnonic triple nodal points. The quasiparticle excitations near the triple nodal points represent three-component bosons beyond that of magnonic Dirac, Weyl, and nodal-line cases. They can be regarded as a direct reflection of the intrinsic spin carried by magnons. Furthermore, we show that the magnonic triple nodal points can split into magnonic Weyl points, as the system transits from a non-collinear spin structure to a non-coplanar one with a non-zero scalar spin chirality. Our results not only apply to insulating antiferromagnets, but also provide a platform to seek for triple nodal points in metallic antiferromagnets.

  18. Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice

    Science.gov (United States)

    Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.

    2012-01-01

    Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542

  19. BRCA2 hypomorphic missense variants confer moderate risks of breast cancer

    OpenAIRE

    Shimelis, Hermela; Mesman, Romy L.s.; Von Nicolai, Catharina; Ehlen, Asa; Guidugli, Lucia; Martin, Charlotte; Calleja, Fabienne Mgr; Meeks, Huong; Hallberg, Emily; Hinton, Jamie; Lilyquist, Jenna; Hu, Chunling; Aalfs, Cora M; Aittomaki, Kristiina; Andrulis, Irene L.

    2017-01-01

    Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ances...

  20. BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.

    OpenAIRE

    Shimelis, Hermela; Mesman, Romy LS; Von, Nicolai Catharina; Ehlen, Asa; Guidugli, Lucia; Martin, Charlotte; Calléja, Fabienne MGR; Meeks, Huong; Hallberg, Emily; Hinton, Jamie; Lilyquist, Jenna; Hu, Chunling; Aalfs, Cora M; Aittomäki, Kristiina; Andrulis, Irene

    2017-01-01

    Breast cancer risks conferred by many germline missense variants in the $\\textit{BRCA1}$ and $\\textit{BRCA2}$ genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine ...

  1. Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance.

    Science.gov (United States)

    Payne, Felicity; Colnaghi, Rita; Rocha, Nuno; Seth, Asha; Harris, Julie; Carpenter, Gillian; Bottomley, William E; Wheeler, Eleanor; Wong, Stephen; Saudek, Vladimir; Savage, David; O'Rahilly, Stephen; Carel, Jean-Claude; Barroso, Inês; O'Driscoll, Mark; Semple, Robert

    2014-09-01

    Structural maintenance of chromosomes (SMC) complexes are essential for maintaining chromatin structure and regulating gene expression. Two the three known SMC complexes, cohesin and condensin, are important for sister chromatid cohesion and condensation, respectively; however, the function of the third complex, SMC5-6, which includes the E3 SUMO-ligase NSMCE2 (also widely known as MMS21) is less clear. Here, we characterized 2 patients with primordial dwarfism, extreme insulin resistance, and gonadal failure and identified compound heterozygous frameshift mutations in NSMCE2. Both mutations reduced NSMCE2 expression in patient cells. Primary cells from one patient showed increased micronucleus and nucleoplasmic bridge formation, delayed recovery of DNA synthesis, and reduced formation of foci containing Bloom syndrome helicase (BLM) after hydroxyurea-induced replication fork stalling. These nuclear abnormalities in patient dermal fibroblast were restored by expression of WT NSMCE2, but not a mutant form lacking SUMO-ligase activity. Furthermore, in zebrafish, knockdown of the NSMCE2 ortholog produced dwarfism, which was ameliorated by reexpression of WT, but not SUMO-ligase-deficient NSMCE. Collectively, these findings support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress.

  2. No evidence for cumulative effects in a Dnmt3b hypomorph across multiple generations

    Czech Academy of Sciences Publication Activity Database

    Youngson, N.A.; Epp, Trevor; Roberts, A.R.; Daxinger, L.; Ashe, A.; Huang, E.; Lester, K.L.; Harten, S.K.; Kay, G.F.; Cox, T.; Matthews, J.M.; Chong, S.; Whitelaw, E.

    2013-01-01

    Roč. 24, 5-6 (2013), s. 206-217 ISSN 0938-8990 Institutional support: RVO:68378050 Keywords : epigenetic inheritance * mammalian development * transgenerational Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.883, year: 2013

  3. Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation.

    Science.gov (United States)

    Staines, Katherine A; Javaheri, Behzad; Hohenstein, Peter; Fleming, Robert; Ikpegbu, Ekele; Unger, Erin; Hopkinson, Mark; Buttle, David J; Pitsillides, Andrew A; Farquharson, Colin

    2017-11-01

    The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone-specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpn flox/flox (cKO) mice and their Pdpn flox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  4. BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer

    NARCIS (Netherlands)

    Shimelis, Hermela; Mesman, Romy L. S.; Von Nicolai, Catharina; Ehlen, Asa; Guidugli, Lucia; Martin, Charlotte; Calléja, Fabienne M. G. R.; Meeks, Huong; Hallberg, Emily; Hinton, Jamie; Lilyquist, Jenna; Hu, Chunling; Aalfs, Cora M.; Aittomäki, Kristiina; Andrulis, Irene; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Brouwers, Barbara; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Cheng, Ching-Yu; Choi, Ji-Yeob; Collée, J. Margriet; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M.; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G.; Glendon, Gord; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Hartman, Mikael; Hogervorst, Frans B.; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lai, Kah-Nyin; Lambrechts, Diether; Marchand, Loic Le; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Machackova, Eva; Mannermaa, Arto; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; Miao, Hui; Michailidou, Kyriaki; Milne, Roger L.; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Olson, Janet E.; Olswold, Curtis; Oosterwijk, Jan J. C.; Osorio, Ana; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D. P.; Pylkäs, Katri; Radice, Paolo; Rashid, Muhammad Usman; Rhenius, Valerie; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schoemaker, Minouk J.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shrubsole, Martha; Shu, Xiao-Ou; Slager, Susan; Southey, Melissa C.; Stram, Daniel O.; Swerdlow, Anthony; teo, Soo H.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; van Asperen, Christi J.; van der Kolk, Lizet E.; Wang, Qin; Winqvist, Robert; Wu, Anna H.; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Leary, Jennifer; Walker, Logan; Foretova, Lenka; Fostira, Florentia; Claes, Kathleen B. M.; Varesco, Liliana; Moghadasi, Setareh; Easton, Douglas F.; Spurdle, Amanda; Devilee, Peter; Vrieling, Harry; Monteiro, Alvaro N. A.; Goldgar, David E.; Carreira, Aura; Vreeswijk, Maaike P. G.; Couch, Fergus J.

    2017-01-01

    Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk

  5. BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer

    DEFF Research Database (Denmark)

    Shimelis, Hermela; Mesman, Romy L S; Von Nicolai, Catharina

    2017-01-01

    Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk ......, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR....... were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA...... of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant...

  6. Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

    NARCIS (Netherlands)

    Hassane, S.; Claij, N.; Lantinga-van Leeuwen, I.S.; Munsteren, J.C. van; Lent, N. van; Hanemaaijer, R.; Breuning, M.H.; Peters, D.J.M.; Ruiter, M.C. de

    2007-01-01

    OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have

  7. Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Patrick A. Vigueira

    2014-06-01

    Full Text Available Carrier-facilitated pyruvate transport across the inner mitochondrial membrane plays an essential role in anabolic and catabolic intermediary metabolism. Mitochondrial pyruvate carrier 2 (Mpc2 is believed to be a component of the complex that facilitates mitochondrial pyruvate import. Complete MPC2 deficiency resulted in embryonic lethality in mice. However, a second mouse line expressing an N-terminal truncated MPC2 protein (Mpc2Δ16 was viable but exhibited a reduced capacity for mitochondrial pyruvate oxidation. Metabolic studies demonstrated exaggerated blood lactate concentrations after pyruvate, glucose, or insulin challenge in Mpc2Δ16 mice. Additionally, compared with wild-type controls, Mpc2Δ16 mice exhibited normal insulin sensitivity but elevated blood glucose after bolus pyruvate or glucose injection. This was attributable to reduced glucose-stimulated insulin secretion and was corrected by sulfonylurea KATP channel inhibitor administration. Collectively, these data are consistent with a role for MPC2 in mitochondrial pyruvate import and suggest that Mpc2 deficiency results in defective pancreatic β cell glucose sensing.

  8. Making SharePoint® Chemically Aware™.

    Science.gov (United States)

    Tallapragada, Kartik; Chewning, Joseph; Kombo, David; Ludwick, Beverly

    2012-01-12

    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. 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. 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 researchers to find information which was once difficult to find

  9. 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

  10. Role of Erosion in Shaping Point Bars

    Science.gov (United States)

    Moody, J.; Meade, R.

    2012-04-01

    A powerful metaphor in fluvial geomorphology has been that depositional features such as point bars (and other floodplain features) constitute the river's historical memory in the form of uniformly thick sedimentary deposits waiting for the geomorphologist to dissect and interpret the past. For the past three decades, along the channel of Powder River (Montana USA) we have documented (with annual cross-sectional surveys and pit trenches) the evolution of the shape of three point bars that were created when an extreme flood in 1978 cut new channels across the necks of two former meander bends and radically shifted the location of a third bend. Subsequent erosion has substantially reshaped, at different time scales, the relic sediment deposits of varying age. At the weekly to monthly time scale (i.e., floods from snowmelt or floods from convective or cyclonic storms), the maximum scour depth was computed (by using a numerical model) at locations spaced 1 m apart across the entire point bar for a couple of the largest floods. The maximum predicted scour is about 0.22 m. At the annual time scale, repeated cross-section topographic surveys (25 during 32 years) indicate that net annual erosion at a single location can be as great as 0.5 m, and that the net erosion is greater than net deposition during 8, 16, and 32% of the years for the three point bars. On average, the median annual net erosion was 21, 36, and 51% of the net deposition. At the decadal time scale, an index of point bar preservation often referred to as completeness was defined for each cross section as the percentage of the initial deposit (older than 10 years) that was still remaining in 2011; computations indicate that 19, 41, and 36% of the initial deposits of sediment were eroded. Initial deposits were not uniform in thickness and often represented thicker pods of sediment connected by thin layers of sediment or even isolated pods at different elevations across the point bar in response to multiple

  11. Hardware-accelerated Point Generation and Rendering of Point-based Impostors

    DEFF Research Database (Denmark)

    Bærentzen, Jakob Andreas

    2005-01-01

    This paper presents a novel scheme for generating points from triangle models. The method is fast and lends itself well to implementation using graphics hardware. The triangle to point conversion is done by rendering the models, and the rendering may be performed procedurally or by a black box API....... I describe the technique in detail and discuss how the generated point sets can easily be used as impostors for the original triangle models used to create the points. Since the points reside solely in GPU memory, these impostors are fairly efficient. Source code is available online....

  12. Inhibition effect of calcium hydroxide point and chlorhexidine point on root canal bacteria of necrosis teeth

    Directory of Open Access Journals (Sweden)

    Andry Leonard Je

    2006-03-01

    Full Text Available Calcium Hydroxide point and Chlorhexidine point are new drugs for eliminating bacteria in the root canal. The points slowly and controly realease Calcium Hydroxide and Chlorhexidine into root canal. The purpose of the study was to determined the effectivity of Calcium hydroxide point (Calcium hydroxide plus point and Chlorhexidine point in eleminating the root canal bacteria of nescrosis teeth. In this study 14 subjects were divided into 2 groups. The first group was treated with Calcium hydroxide point and the second was treated with Chlorhexidine poin. The bacteriological sampling were measured with spectrofotometry. The Paired T Test analysis (before and after showed significant difference between the first and second group. The Independent T Test which analysed the effectivity of both groups had not showed significant difference. Although there was no significant difference in statistical test, the result of second group eliminate more bacteria than the first group. The present finding indicated that the use of Chlorhexidine point was better than Calcium hydroxide point in seven days period. The conclusion is Chlorhexidine point and Calcium hydroxide point as root canal medicament effectively eliminate root canal bacteria of necrosis teeth.

  13. The computation of fixed points and applications

    CERN Document Server

    Todd, Michael J

    1976-01-01

    Fixed-point algorithms have diverse applications in economics, optimization, game theory and the numerical solution of boundary-value problems. Since Scarf's pioneering work [56,57] on obtaining approximate fixed points of continuous mappings, a great deal of research has been done in extending the applicability and improving the efficiency of fixed-point methods. Much of this work is available only in research papers, although Scarf's book [58] gives a remarkably clear exposition of the power of fixed-point methods. However, the algorithms described by Scarf have been super~eded by the more sophisticated restart and homotopy techniques of Merrill [~8,~9] and Eaves and Saigal [1~,16]. To understand the more efficient algorithms one must become familiar with the notions of triangulation and simplicial approxi- tion, whereas Scarf stresses the concept of primitive set. These notes are intended to introduce to a wider audience the most recent fixed-point methods and their applications. Our approach is therefore ...

  14. An X-point ergodic divertor

    International Nuclear Information System (INIS)

    Chu, M.S.; Jensen, T.H.; La Haye, R.J.; Taylor, T.S.; Evans, T.E.

    1991-10-01

    A new ergodic divertor is proposed. It utilizes a system of external (n = 3) coils arranged to generate overlapping magnetic islands in the edge region of a diverted tokamak and connect the randomized field lines to the external (cold) divertor plate. The novel feature in the configuration is the placement of the external coils close to the X-point. A realistic design of the external coil set is studied by using the field line tracing method for a low aspect ratio (A ≅ 3) tokamak. Two types of effects are observed. First, by placing the coils close to the X-point, where the poloidal magnetic field is weak and the rational surfaces are closely packed only a moderate amount of current in the external coils is needed to ergodize the edge region. This ergodized edge enhances the edge transport in the X-point region and leads to the potential of edge profile control and the avoidance of edge localized modes (ELMs). Furthermore, the trajectories of the field lines close to the X-point are modified by the external coil set, causing the hit points on the external divertor plates to be randomized and spread out in the major radius direction. A time-dependent modulation of the currents in the external (n = 3) coils can potentially spread the heat flux more uniformly on the divertor plate avoiding high concentration of the heat flux. 10 refs., 9 figs

  15. Critical Points in Distance Learning System

    Directory of Open Access Journals (Sweden)

    Airina Savickaitė

    2013-08-01

    Full Text Available Purpose – This article presents the results of distance learning system analysis, i.e. the critical elements of the distance learning system. The critical points of distance learning are a part of distance education online environment interactivity/community process model. The most important is the fact that the critical point is associated with distance learning participants. Design/methodology/approach – Comparative review of articles and analysis of distance learning module. Findings – A modern man is a lifelong learner and distance learning is a way to be a modern person. The focus on a learner and feedback is the most important thing of learning distance system. Also, attention should be paid to the lecture-appropriate knowledge and ability to convey information. Distance system adaptation is the way to improve the learner’s learning outcomes. Research limitations/implications – Different learning disciplines and learning methods may have different critical points. Practical implications – The information of analysis could be important for both lecturers and students, who studies distance education systems. There are familiar critical points which may deteriorate the quality of learning. Originality/value – The study sought to develop remote systems for applications in order to improve the quality of knowledge. Keywords: distance learning, process model, critical points. Research type: review of literature and general overview.

  16. Geometric Spanners for Weighted Point Sets

    DEFF Research Database (Denmark)

    Abam, Mohammad; de Berg, Mark; Farshi, Mohammad

    2009-01-01

    Let (S,d) be a finite metric space, where each element p ∈ S has a non-negative weight w(p). We study spanners for the set S with respect to weighted distance function d w , where d w (p,q) is w(p) + d(p,q) + wq if p ≠ q and 0 otherwise. We present a general method for turning spanners with respect...... to the d-metric into spanners with respect to the d w -metric. For any given ε> 0, we can apply our method to obtain (5 + ε)-spanners with a linear number of edges for three cases: points in Euclidean space ℝ d , points in spaces of bounded doubling dimension, and points on the boundary of a convex body...... in ℝ d where d is the geodesic distance function. We also describe an alternative method that leads to (2 + ε)-spanners for points in ℝ d and for points on the boundary of a convex body in ℝ d . The number of edges in these spanners is O(nlogn). This bound on the stretch factor is nearly optimal...

  17. SMART POINT CLOUD: DEFINITION AND REMAINING CHALLENGES

    Directory of Open Access Journals (Sweden)

    F. Poux

    2016-10-01

    Full Text Available Dealing with coloured point cloud acquired from terrestrial laser scanner, this paper identifies remaining challenges for a new data structure: the smart point cloud. This concept arises with the statement that massive and discretized spatial information from active remote sensing technology is often underused due to data mining limitations. The generalisation of point cloud data associated with the heterogeneity and temporality of such datasets is the main issue regarding structure, segmentation, classification, and interaction for an immediate understanding. We propose to use both point cloud properties and human knowledge through machine learning to rapidly extract pertinent information, using user-centered information (smart data rather than raw data. A review of feature detection, machine learning frameworks and database systems indexed both for mining queries and data visualisation is studied. Based on existing approaches, we propose a new 3-block flexible framework around device expertise, analytic expertise and domain base reflexion. This contribution serves as the first step for the realisation of a comprehensive smart point cloud data structure.

  18. Fixed point theory in metric type spaces

    CERN Document Server

    Agarwal, Ravi P; O’Regan, Donal; Roldán-López-de-Hierro, Antonio Francisco

    2015-01-01

    Written by a team of leading experts in the field, this volume presents a self-contained account of the theory, techniques and results in metric type spaces (in particular in G-metric spaces); that is, the text approaches this important area of fixed point analysis beginning from the basic ideas of metric space topology. The text is structured so that it leads the reader from preliminaries and historical notes on metric spaces (in particular G-metric spaces) and on mappings, to Banach type contraction theorems in metric type spaces, fixed point theory in partially ordered G-metric spaces, fixed point theory for expansive mappings in metric type spaces, generalizations, present results and techniques in a very general abstract setting and framework. Fixed point theory is one of the major research areas in nonlinear analysis. This is partly due to the fact that in many real world problems fixed point theory is the basic mathematical tool used to establish the existence of solutions to problems which arise natur...

  19. Controlling superconductivity by tunable quantum critical points.

    Science.gov (United States)

    Seo, S; Park, E; Bauer, E D; Ronning, F; Kim, J N; Shim, J-H; Thompson, J D; Park, Tuson

    2015-03-04

    The heavy fermion compound CeRhIn5 is a rare example where a quantum critical point, hidden by a dome of superconductivity, has been explicitly revealed and found to have a local nature. The lack of additional examples of local types of quantum critical points associated with superconductivity, however, has made it difficult to unravel the role of quantum fluctuations in forming Cooper pairs. Here, we show the precise control of superconductivity by tunable quantum critical points in CeRhIn5. Slight tin-substitution for indium in CeRhIn5 shifts its antiferromagnetic quantum critical point from 2.3 GPa to 1.3 GPa and induces a residual impurity scattering 300 times larger than that of pure CeRhIn5, which should be sufficient to preclude superconductivity. Nevertheless, superconductivity occurs at the quantum critical point of the tin-doped metal. These results underline that fluctuations from the antiferromagnetic quantum criticality promote unconventional superconductivity in CeRhIn5.

  20. CLASSIFICATION BY USING MULTISPECTRAL POINT CLOUD DATA

    Directory of Open Access Journals (Sweden)

    C. T. Liao

    2012-07-01

    Full Text Available Remote sensing images are generally recorded in two-dimensional format containing multispectral information. Also, the semantic information is clearly visualized, which ground features can be better recognized and classified via supervised or unsupervised classification methods easily. Nevertheless, the shortcomings of multispectral images are highly depending on light conditions, and classification results lack of three-dimensional semantic information. On the other hand, LiDAR has become a main technology for acquiring high accuracy point cloud data. The advantages of LiDAR are high data acquisition rate, independent of light conditions and can directly produce three-dimensional coordinates. However, comparing with multispectral images, the disadvantage is multispectral information shortage, which remains a challenge in ground feature classification through massive point cloud data. Consequently, by combining the advantages of both LiDAR and multispectral images, point cloud data with three-dimensional coordinates and multispectral information can produce a integrate solution for point cloud classification. Therefore, this research acquires visible light and near infrared images, via close range photogrammetry, by matching images automatically through free online service for multispectral point cloud generation. Then, one can use three-dimensional affine coordinate transformation to compare the data increment. At last, the given threshold of height and color information is set as threshold in classification.

  1. Classification by Using Multispectral Point Cloud Data

    Science.gov (United States)

    Liao, C. T.; Huang, H. H.

    2012-07-01

    Remote sensing images are generally recorded in two-dimensional format containing multispectral information. Also, the semantic information is clearly visualized, which ground features can be better recognized and classified via supervised or unsupervised classification methods easily. Nevertheless, the shortcomings of multispectral images are highly depending on light conditions, and classification results lack of three-dimensional semantic information. On the other hand, LiDAR has become a main technology for acquiring high accuracy point cloud data. The advantages of LiDAR are high data acquisition rate, independent of light conditions and can directly produce three-dimensional coordinates. However, comparing with multispectral images, the disadvantage is multispectral information shortage, which remains a challenge in ground feature classification through massive point cloud data. Consequently, by combining the advantages of both LiDAR and multispectral images, point cloud data with three-dimensional coordinates and multispectral information can produce a integrate solution for point cloud classification. Therefore, this research acquires visible light and near infrared images, via close range photogrammetry, by matching images automatically through free online service for multispectral point cloud generation. Then, one can use three-dimensional affine coordinate transformation to compare the data increment. At last, the given threshold of height and color information is set as threshold in classification.

  2. Turning points in the history of mathematics

    CERN Document Server

    Grant, Hardy

    2015-01-01

    This book explores some of the major turning points in the history of mathematics, ranging from ancient Greece to the present, demonstrating the drama that has often been a part of its evolution. Studying these breakthroughs, transitions, and revolutions, their stumbling-blocks and their triumphs, can help illuminate the importance of the history of mathematics for its teaching, learning, and appreciation. Some of the turning points considered are the rise of the axiomatic method (most famously in Euclid), and the subsequent major changes in it (for example, by David Hilbert); the “wedding,” via analytic geometry, of algebra and geometry; the “taming” of the infinitely small and the infinitely large; the passages from algebra to algebras, from geometry to geometries, and from arithmetic to arithmetics; and the revolutions in the late nineteenth and early twentieth centuries that resulted from Georg Cantor’s creation of transfinite set theory. The origin of each turning point is discussed, along with...

  3. Generalized Attractor Points in Gauged Supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Kachru, Shamit; /Stanford U., Phys. Dept. /SLAC; Kallosh, Renata; /Stanford U., Phys. Dept.; Shmakova, Marina; /KIPAC, Menlo Park /SLAC /Stanford U., Phys. Dept.

    2011-08-15

    The attractor mechanism governs the near-horizon geometry of extremal black holes in ungauged 4D N=2 supergravity theories and in Calabi-Yau compactifications of string theory. In this paper, we study a natural generalization of this mechanism to solutions of arbitrary 4D N=2 gauged supergravities. We define generalized attractor points as solutions of an ansatz which reduces the Einstein, gauge field, and scalar equations of motion to algebraic equations. The simplest generalized attractor geometries are characterized by non-vanishing constant anholonomy coefficients in an orthonormal frame. Basic examples include Lifshitz and Schroedinger solutions, as well as AdS and dS vacua. There is a generalized attractor potential whose critical points are the attractor points, and its extremization explains the algebraic nature of the equations governing both supersymmetric and non-supersymmetric attractors.

  4. The Pervasive Power of PowerPoint

    DEFF Research Database (Denmark)

    Schoeneborn, Dennis

    2013-01-01

    This paper examines the pervasive role of Microsoft’s presentation software PowerPoint as a genre of professional and organizational communication. Frequently, PowerPoint is not only used for the primary function it was initially designed for, i.e., facilitating live presentations, but also...... for alternative purposes such as project documentation. Its application in a neighboring domain, however, poses a functional dilemma: does the PowerPoint genre preserve the features of its primary function, i.e., presentation, or rather adapt to the new function, i.e., documentation? By drawing on a communication......-centered perspective, this paper examines PowerPoint’s role in the domain of project documentation as a clash between the constitutive affordances of professional and of organizational communication. To investigate this issue empirically, I conducted a case study at a multinational business consulting firm. The study...

  5. Automatic dew-point temperature sensor.

    Science.gov (United States)

    Graichen, H; Rascati, R; Gonzalez, R R

    1982-06-01

    A device is described for measuring dew-point temperature and water vapor pressure in small confined areas. The method is based on the deposition of water on a cooled surface when at dew-point temperature. A small Peltier module lowers the temperature of two electrically conductive plates. At dew point the insulating gap separating the plates becomes conductive as water vapor condenses. Sensors based on this principle can be made small and rugged and can be used for measuring directly the local water vapor pressure. They may be installed within a conventional ventilated sweat capsule used for measuring water vapor loss from the skin surface. A novel application is the measurement of the water vapor pressure gradients across layers of clothing worn by an exercising subject.

  6. Early warning of climate tipping points

    Science.gov (United States)

    Lenton, Timothy M.

    2011-07-01

    A climate 'tipping point' occurs when a small change in forcing triggers a strongly nonlinear response in the internal dynamics of part of the climate system, qualitatively changing its future state. Human-induced climate change could push several large-scale 'tipping elements' past a tipping point. Candidates include irreversible melt of the Greenland ice sheet, dieback of the Amazon rainforest and shift of the West African monsoon. Recent assessments give an increased probability of future tipping events, and the corresponding impacts are estimated to be large, making them significant risks. Recent work shows that early warning of an approaching climate tipping point is possible in principle, and could have considerable value in reducing the risk that they pose.

  7. QCD and the chiral critical point

    International Nuclear Information System (INIS)

    Gavin, S.; Gocksch, A.; Pisarski, R.D.

    1994-01-01

    As an extension of QCD, consider a theory with ''2+1'' flavors, where the current quark masses are held in a fixed ratio as the overall scale of the quark masses is varied. At nonzero temperature and baryon density it is expected that in the chiral limit the chiral phase transition is of first order. Increasing the quark mass from zero, the chiral transition becomes more weakly first order, and can end in a chiral critical point. We show that the only massless field at the chiral critical point is a σ meson, with the universality class that of the Ising model. Present day lattice simulations indicate that QCD is (relatively) near to the chiral critical point

  8. Fixed point algebras for easy quantum groups

    DEFF Research Database (Denmark)

    Gabriel, Olivier; Weber, Moritz

    2016-01-01

    Compact matrix quantum groups act naturally on Cuntz algebras. The first author isolated certain conditions under which the fixed point algebras under this action are Kirchberg algebras. Hence they are completely determined by their K-groups. Building on prior work by the second author,we prove...... that free easy quantum groups satisfy these conditions and we compute the K-groups of their fixed point algebras in a general form. We then turn to examples such as the quantum permutation group S+ n,the free orthogonal quantum group O+ n and the quantum reflection groups Hs+ n. Our fixed point......-algebra construction provides concrete examples of free actions of free orthogonal easy quantum groups,which are related to Hopf-Galois extensions....

  9. Zero-point field in curved spaces

    International Nuclear Information System (INIS)

    Hacyan, S.; Sarmiento, A.; Cocho, G.; Soto, F.

    1985-01-01

    Boyer's conjecture that the thermal effects of acceleration are manifestations of the zero-point field is further investigated within the context of quantum field theory in curved spaces. The energy-momentum current for a spinless field is defined rigorously and used as the basis for investigating the energy density observed in a noninertial frame. The following examples are considered: (i) uniformly accelerated observers, (ii) two-dimensional Schwarzschild black holes, (iii) the Einstein universe. The energy spectra which have been previously calculated appear in the present formalism as an additional contribution to the energy of the zero-point field, but particle creation does not occur. It is suggested that the radiation produced by gravitational fields or by acceleration is a manifestation of the zero-point field and of the same nature (whether real or virtual)

  10. Point defects and atomic transport in crystals

    International Nuclear Information System (INIS)

    Lidiard, A.B.

    1981-02-01

    There are two principle aspects to the theory of atomic transport in crystals as caused by the action of point defects, namely (1) the calculation of relevant properties of the point defects (energies and other thermodynamic characteristics of the different possible defects, activation energies and other mobility parameters) and (2) the statistical mechanics of assemblies of defects, both equilibrium and non-equilibrium assemblies. In the five lectures given here both these aspects are touched on. The first two lectures are concerned with the calculation of relevant point defect properties, particularly in ionic crystals. The first lecture is more general, the second is concerned particularly with some recent calculations of the free volumes of formation of defects in various ionic solids; these solve a rather long-standing problem in this area. The remaining three lectures are concerned with the kinetic theory of defects mainly in relaxation, drift and diffusion situations

  11. Nanotexturing of surfaces to reduce melting point.

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Ernest J.; Zubia, David (University of Texas at El Paso El Paso, TX); Mireles, Jose (Universidad Aut%C3%94onoma de Ciudad Ju%C3%94arez Ciudad Ju%C3%94arez, Mexico); Marquez, Noel (University of Texas at El Paso El Paso, TX); Quinones, Stella (University of Texas at El Paso El Paso, TX)

    2011-11-01

    This investigation examined the use of nano-patterned structures on Silicon-on-Insulator (SOI) material to reduce the bulk material melting point (1414 C). It has been found that sharp-tipped and other similar structures have a propensity to move to the lower energy states of spherical structures and as a result exhibit lower melting points than the bulk material. Such a reduction of the melting point would offer a number of interesting opportunities for bonding in microsystems packaging applications. Nano patterning process capabilities were developed to create the required structures for the investigation. One of the technical challenges of the project was understanding and creating the specialized conditions required to observe the melting and reshaping phenomena. Through systematic experimentation and review of the literature these conditions were determined and used to conduct phase change experiments. Melting temperatures as low as 1030 C were observed.

  12. End-point sharpness in thermometric titrimetry.

    Science.gov (United States)

    Tyrrell, H J

    1967-07-01

    It is shown that the sharpness of an end-point in a thermometric titration where the simple reaction A + B right harpoon over left harpoon AB takes place, depends on Kc(A') where K is the equilibrium constant for the reaction, and c(A') is the total concentration of the titrand (A) in the reaction mixture. The end-point is sharp if, (i) the enthalpy change in the reaction is not negligible, and (ii) Kc(A') > 10(3). This shows that it should, for example, be possible to titrate 0.1 M acid, pK(A) = 10, using a thennometric end-point. Some aspects of thermometric titrimetry when Kc(A') < 10(3) are also considered.

  13. Visibility of noisy point cloud data

    KAUST Repository

    Mehra, Ravish

    2010-06-01

    We present a robust algorithm for estimating visibility from a given viewpoint for a point set containing concavities, non-uniformly spaced samples, and possibly corrupted with noise. Instead of performing an explicit surface reconstruction for the points set, visibility is computed based on a construction involving convex hull in a dual space, an idea inspired by the work of Katz et al. [26]. We derive theoretical bounds on the behavior of the method in the presence of noise and concavities, and use the derivations to develop a robust visibility estimation algorithm. In addition, computing visibility from a set of adaptively placed viewpoints allows us to generate locally consistent partial reconstructions. Using a graph based approximation algorithm we couple such reconstructions to extract globally consistent reconstructions. We test our method on a variety of 2D and 3D point sets of varying complexity and noise content. © 2010 Elsevier Ltd. All rights reserved.

  14. Optimizing Probability of Detection Point Estimate Demonstration

    Science.gov (United States)

    Koshti, Ajay M.

    2017-01-01

    Probability of detection (POD) analysis is used in assessing reliably detectable flaw size in nondestructive evaluation (NDE). MIL-HDBK-18231and associated mh18232POD software gives most common methods of POD analysis. Real flaws such as cracks and crack-like flaws are desired to be detected using these NDE methods. A reliably detectable crack size is required for safe life analysis of fracture critical parts. The paper provides discussion on optimizing probability of detection (POD) demonstration experiments using Point Estimate Method. POD Point estimate method is used by NASA for qualifying special NDE procedures. The point estimate method uses binomial distribution for probability density. Normally, a set of 29 flaws of same size within some tolerance are used in the demonstration. The optimization is performed to provide acceptable value for probability of passing demonstration (PPD) and achieving acceptable value for probability of false (POF) calls while keeping the flaw sizes in the set as small as possible.

  15. ELEVATION ON BOINLING POINT OF COFFE EXTRACT

    Directory of Open Access Journals (Sweden)

    Telis-Romero J.

    2002-01-01

    Full Text Available The rise in boiling point of coffee extract was experimentally measured at soluble solids concentrations in the range of 9.2 to 52.4ºBrix and pressures between 5.8 × 10³ and 9.4 × 10(4 Pa (abs.. Different approaches to representing experimental data, including the Dühring's rule, the Antoine equation and empirical models proposed in the literature were tested. In the range of 9.2 to 16.2ºBrix, the rise in boiling point was nearly independent of pressure, varying only with extract concentration. Considerable deviations of this behavior began to occur at concentrations higher than 16.2ºBrix. Experimental data could best be predicted by adjusting an empirical model which consists of a single equation that takes into account the dependence of rise in boiling point on pressure and concentration.

  16. Theory of Single Point Incremental Forming

    DEFF Research Database (Denmark)

    Martins, P.A.F.; Bay, Niels; Skjødt, Martin

    2008-01-01

    This paper presents a closed-form theoretical analysis modelling the fundamentals of single point incremental forming and explaining the experimental and numerical results available in the literature for the past couple of years. The model is based on membrane analysis with bi-directional in-plan......-plane contact friction and is focused on the extreme modes of deformation that are likely to be found in single point incremental forming processes. The overall investigation is supported by experimental work performed by the authors and data retrieved from the literature.......This paper presents a closed-form theoretical analysis modelling the fundamentals of single point incremental forming and explaining the experimental and numerical results available in the literature for the past couple of years. The model is based on membrane analysis with bi-directional in...

  17. Problems in the theory of point explosions

    Science.gov (United States)

    Korobeinikov, V. P.

    The book is concerned with the development of the theory of point explosions, which is relevant to the study of such phenomena as the initiation of detonation, high-power explosions, electric discharges, cosmic explosions, laser blasts, and hypersonic aerodynamics. The discussion covers the principal equations and the statement of problems; linearized non-self-similar one-dimensional problems; spherical, cylindrical, and plane explosions with allowance for counterpressure under conditions of constant initial density; explosions in a combustible mixture of gases; and point explosions in inhomogeneous media with nonsymmetric energy release. Attention is also given to point explosions in an electrically conducting gas with allowance for the effect of the magnetic field and to the propagation of perturbations from solar flares.

  18. Life satisfaction set point: stability and change.

    Science.gov (United States)

    Fujita, Frank; Diener, Ed

    2005-01-01

    Using data from 17 years of a large and nationally representative panel study from Germany, the authors examined whether there is a set point for life satisfaction (LS)--stability across time, even though it can be perturbed for short periods by life events. The authors found that 24% of respondents changed significantly in LS from the first 5 years to the last 5 years and that stability declined as the period between measurements increased. Average LS in the first 5 years correlated .51 with the 5-year average of LS during the last 5 years. Height, weight, body mass index, systolic and diastolic blood pressure, and personality traits were all more stable than LS, whereas income was about as stable as LS. Almost 9% of the sample changed an average of 3 or more points on a 10-point scale from the first 5 to last 5 years of the study.

  19. Reactor coolant flow measurements at Point Lepreau

    International Nuclear Information System (INIS)

    Brenciaglia, G.; Gurevich, Y.; Liu, G.

    1996-01-01

    The CROSSFLOW ultrasonic flow measurement system manufactured by AMAG is fully proven as reliable and accurate when applied to large piping in defined geometries for such applications as feedwater flows measurement. Its application to direct reactor coolant flow (RCF) measurements - both individual channel flows and bulk flows such as pump suction flow - has been well established through recent work by AMAG at Point Lepreau, with application to other reactor types (eg. PWR) imminent. At Point Lepreau, Measurements have been demonstrated at full power; improvements to consistently meet ±1% accuracy are in progress. The development and recent customization of CROSSFLOW to RCF measurement at Point Lepreau are described in this paper; typical measurement results are included. (author)

  20. The registration of non-cooperative moving targets laser point cloud in different view point

    Science.gov (United States)

    Wang, Shuai; Sun, Huayan; Guo, Huichao

    2018-01-01

    Non-cooperative moving target multi-view cloud registration is the key technology of 3D reconstruction of laser threedimension imaging. The main problem is that the density changes greatly and noise exists under different acquisition conditions of point cloud. In this paper, firstly, the feature descriptor is used to find the most similar point cloud, and then based on the registration algorithm of region segmentation, the geometric structure of the point is extracted by the geometric similarity between point and point, The point cloud is divided into regions based on spectral clustering, feature descriptors are created for each region, searching to find the most similar regions in the most similar point of view cloud, and then aligning the pair of point clouds by aligning their minimum bounding boxes. Repeat the above steps again until registration of all point clouds is completed. Experiments show that this method is insensitive to the density of point clouds and performs well on the noise of laser three-dimension imaging.

  1. Point Cluster Analysis Using a 3D Voronoi Diagram with Applications in Point Cloud Segmentation

    Directory of Open Access Journals (Sweden)

    Shen Ying

    2015-08-01

    Full Text Available Three-dimensional (3D point analysis and visualization is one of the most effective methods of point cluster detection and segmentation in geospatial datasets. However, serious scattering and clotting characteristics interfere with the visual detection of 3D point clusters. To overcome this problem, this study proposes the use of 3D Voronoi diagrams to analyze and visualize 3D points instead of the original data item. The proposed algorithm computes the cluster of 3D points by applying a set of 3D Voronoi cells to describe and quantify 3D points. The decompositions of point cloud of 3D models are guided by the 3D Voronoi cell parameters. The parameter values are mapped from the Voronoi cells to 3D points to show the spatial pattern and relationships; thus, a 3D point cluster pattern can be highlighted and easily recognized. To capture different cluster patterns, continuous progressive clusters and segmentations are tested. The 3D spatial relationship is shown to facilitate cluster detection. Furthermore, the generated segmentations of real 3D data cases are exploited to demonstrate the feasibility of our approach in detecting different spatial clusters for continuous point cloud segmentation.

  2. Point cloud processing for smart systems

    Directory of Open Access Journals (Sweden)

    Jaromír Landa

    2013-01-01

    Full Text Available High population as well as the economical tension emphasises the necessity of effective city management – from land use planning to urban green maintenance. The management effectiveness is based on precise knowledge of the city environment. Point clouds generated by mobile and terrestrial laser scanners provide precise data about objects in the scanner vicinity. From these data pieces the state of the roads, buildings, trees and other objects important for this decision-making process can be obtained. Generally, they can support the idea of “smart” or at least “smarter” cities.Unfortunately the point clouds do not provide this type of information automatically. It has to be extracted. This extraction is done by expert personnel or by object recognition software. As the point clouds can represent large areas (streets or even cities, usage of expert personnel to identify the required objects can be very time-consuming, therefore cost ineffective. Object recognition software allows us to detect and identify required objects semi-automatically or automatically.The first part of the article reviews and analyses the state of current art point cloud object recognition techniques. The following part presents common formats used for point cloud storage and frequently used software tools for point cloud processing. Further, a method for extraction of geospatial information about detected objects is proposed. Therefore, the method can be used not only to recognize the existence and shape of certain objects, but also to retrieve their geospatial properties. These objects can be later directly used in various GIS systems for further analyses.

  3. Interior point algorithms theory and analysis

    CERN Document Server

    Ye, Yinyu

    2011-01-01

    The first comprehensive review of the theory and practice of one of today's most powerful optimization techniques. The explosive growth of research into and development of interior point algorithms over the past two decades has significantly improved the complexity of linear programming and yielded some of today's most sophisticated computing techniques. This book offers a comprehensive and thorough treatment of the theory, analysis, and implementation of this powerful computational tool. Interior Point Algorithms provides detailed coverage of all basic and advanced aspects of the subject.

  4. LIDAR, Point Clouds, and their Archaeological Applications

    Energy Technology Data Exchange (ETDEWEB)

    White, Devin A [ORNL

    2013-01-01

    It is common in contemporary archaeological literature, in papers at archaeological conferences, and in grant proposals to see heritage professionals use the term LIDAR to refer to high spatial resolution digital elevation models and the technology used to produce them. The goal of this chapter is to break that association and introduce archaeologists to the world of point clouds, in which LIDAR is only one member of a larger family of techniques to obtain, visualize, and analyze three-dimensional measurements of archaeological features. After describing how point clouds are constructed, there is a brief discussion on the currently available software and analytical techniques designed to make sense of them.

  5. SharePoint 2010 Administration Instant Reference

    CERN Document Server

    Williams, Randy

    2011-01-01

    Fast, accurate answers on SharePoint 2010 administration-in an instant If you're a SharePoint administrator and are looking for fast, accurate, easy-to-understand answers and solutions, then this reference is for you. Thumb tabs, secondary and tertiary tables of contents, and special heading treatments ensure quick and easy ways to find practical solutions on the spot. In addition, quick-reference tables, lists, and step-by-step instruction provide even more helpful information on the day-to-day administration of Microsoft's newest collaboration solution.Features invaluable answers and solutio

  6. The QCD Critical Point and Related Observables

    Energy Technology Data Exchange (ETDEWEB)

    Nahrgang, Marlene

    2016-12-15

    The search for the critical point of QCD in heavy-ion collision experiments has sparked enormous interest with the completion of phase I of the RHIC beam energy scan. Here, I review the basics of the thermodynamics of the QCD phase transition and its implications for experimental multiplicity fluctuations in heavy-ion collisions. Several sources of noncritical fluctuations impact the observables and need to be understood in addition to the critical phenomena. Recent progress has been made in dynamical modeling of critical fluctuations, which ultimately is indispensable to understand potential signals of the QCD critical point in heavy-ion collision.

  7. Twisted vector bundles on pointed nodal curves

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    by identifying the points p1 and p2. If m ≥ 2, let R1,...,Rm−1 be m − 1 copies of the projective line P1 and let xi,yi be two distinct points in Ri. Let R be the nodal curve which arises from the union. R0 ⊔ R1 ⊔···⊔ Rm−1 ⊔ Rm by identifying p1 ∈ R0 and p2 ∈ Rm with x1 ∈ R1 and ym−1 ∈ Rm−1 respectively and by identifying ...

  8. Critical point inequalities and scaling limits

    International Nuclear Information System (INIS)

    Newman, C.M.

    1979-01-01

    A refined and extended version of the Buckingham-Gunton inequality relating various pairs of critical exponents is shown to be valid for a large class of statistical mechanical models. If this inequality is an equality (in the refined sense) and one of the critical exponents has a non-Gaussian value, then any scaling limit must be non-Gaussian. This result clarifies the relationships between the nontriviality of triviality of the scaling limit for ordinary critical points in four dimensions (or tricritical points in three dimensions) and the existence of logarithmic factors in the asymptotics which define the two critical exponents. (orig.) [de

  9. SharePoint 2010 for Project Management

    CERN Document Server

    Sy, Dux

    2012-01-01

    If you were to analyze your team's performance on a typical project, you'd be surprised how much time is wasted on non-productive tasks. This hands-on guide shows you how to work more efficiently by organizing and managing projects with SharePoint 2010. You'll learn how to build a Project Management Information System (PMIS), customized to your project, that can effectively coordinate communication and collaboration among team members. Written by a certified Project Management Professional (PMP) and Microsoft SharePoint MVP with 15 years of IT project management experience, each chapter incl

  10. Supporting Multiple Pointing Devices in Microsoft Windows

    DEFF Research Database (Denmark)

    Westergaard, Michael

    2002-01-01

    In this paper the implementation of a Microsoft Windows driver including APIs supporting multiple pointing devices is presented. Microsoft Windows does not natively support multiple pointing devices controlling independent cursors, and a number of solutions to this have been implemented by us and...... and others. Here we motivate and describe a general solution, and how user applications can use it by means of a framework. The device driver and the supporting APIs will be made available free of charge. Interested parties can contact the author for more information....

  11. Dynamics and mission design near libration points

    CERN Document Server

    Gómez, G; Simo, C; Masdemont, J

    2001-01-01

    This book studies several problems related to the analysis of planned or possible spacecraft missions. It is divided into four chapters. The first chapter is devoted to the computation of quasiperiodic solutions for the motion of a spacecraft near the equilateral points of the Earth-Moon system. The second chapter gives a complete description of the orbits near the collinear point, L 1 , between the Earth and the Sun in the restricted three-body problem (RTBP) model. In the third chapter, methods are developed to compute the nominal orbit and to design and test the control strategy for the qua

  12. Dynamics and mission design near libration points

    CERN Document Server

    Gómez, G; Jorba, A; Masdemont, J

    2001-01-01

    The aim of this book is to explain, analyze and compute the kinds of motions that appear in an extended vicinity of the geometrically defined equilateral points of the Earth-Moon system, as a source of possible nominal orbits for future space missions. The methodology developed here is not specific to astrodynamics problems. The techniques are developed in such a way that they can be used to study problems that can be modeled by dynamical systems. Contents: Global Stability Zones Around the Triangular Libration Points; The Normal Form Around L 5 in the Three-dimensional RTBP; Normal Form of th

  13. Duan's fixed point theorem: Proof and generalization

    Directory of Open Access Journals (Sweden)

    Arkowitz Martin

    2006-01-01

    Full Text Available Let be an H-space of the homotopy type of a connected, finite CW-complex, any map and the th power map. Duan proved that has a fixed point if . We give a new, short and elementary proof of this. We then use rational homotopy to generalize to spaces whose rational cohomology is the tensor product of an exterior algebra on odd dimensional generators with the tensor product of truncated polynomial algebras on even dimensional generators. The role of the power map is played by a -structure as defined by Hemmi-Morisugi-Ooshima. The conclusion is that and each has a fixed point.

  14. UHE point source survey at Cygnus experiment

    International Nuclear Information System (INIS)

    Lu, X.; Yodh, G.B.; Alexandreas, D.E.; Allen, R.C.; Berley, D.; Biller, S.D.; Burman, R.L.; Cady, R.; Chang, C.Y.; Dingus, B.L.; Dion, G.M.; Ellsworth, R.W.; Gilra, M.K.; Goodman, J.A.; Haines, T.J.; Hoffman, C.M.; Kwok, P.; Lloyd-Evans, J.; Nagle, D.E.; Potter, M.E.; Sandberg, V.D.; Stark, M.J.; Talaga, R.L.; Vishwanath, P.R.; Zhang, W.

    1991-01-01

    A new method of searching for UHE point source has been developed. With a data sample of 150 million events, we have surveyed the sky for point sources over 3314 locations (1.4 degree <δ<70.4 degree). It was found that their distribution is consistent with a random fluctuation. In addition, fifty two known potential sources, including pulsars and binary x-ray sources, were studied. The source with the largest positive excess is the Crab Nebula. An excess of 2.5 sigma above the background is observed in a bin of 2.3 degree by 2.5 degree in declination and right ascension respectively

  15. Detecting corner points from digital curves

    International Nuclear Information System (INIS)

    Sarfraz, M.

    2011-01-01

    Corners in digital images give important clues for shape representation, recognition, and analysis. Since dominant information regarding shape is usually available at the corners, they provide important features for various real life applications in the disciplines like computer vision, pattern recognition, computer graphics. Corners are the robust features in the sense that they provide important information regarding objects under translation, rotation and scale change. They are also important from the view point of understanding human perception of objects. They play crucial role in decomposing or describing the digital curves. They are also used in scale space theory, image representation, stereo vision, motion tracking, image matching, building mosaics and font designing systems. If the corner points are identified properly, a shape can be represented in an efficient and compact way with sufficient accuracy. Corner detection schemes, based on their applications, can be broadly divided into two categories: binary (suitable for binary images) and gray level (suitable for gray level images). Corner detection approaches for binary images usually involve segmenting the image into regions and extracting boundaries from those regions that contain them. The techniques for gray level images can be categorized into two classes: (a) Template based and (b) gradient based. The template based techniques utilize correlation between a sub-image and a template of a given angle. A corner point is selected by finding the maximum of the correlation output. Gradient based techniques require computing curvature of an edge that passes through a neighborhood in a gray level image. Many corner detection algorithms have been proposed in the literature which can be broadly divided into two parts. One is to detect corner points from grayscale images and other relates to boundary based corner detection. This contribution mainly deals with techniques adopted for later approach

  16. Zero-point energy of confined fermions

    International Nuclear Information System (INIS)

    Milton, K.A.

    1980-01-01

    A closed form for the reduced Green's function of massless fermions in the interior of a spherical bag is obtained. In terms of this Green's function, the corresponding zero-point or Casimir energy is computed. It is proposed that a resulting quadratic divergence can be absorbed by renormalizing a suitable parameter in the bag model (that is, absorbed by a contact term). The residual Casimir stress is attractive, but smaller than the repulsive Casimir stress of gluons in the model. The result for the total zero-point energy is in substantial disagreement with bag model phenomenological values

  17. The myth of the boiling point.

    Science.gov (United States)

    Chang, Hasok

    2008-01-01

    Around 1800, many reputable scientists reported significant variations in the temperature of pure water boiling under normal atmospheric pressure. The reported variations included a difference of over 1 degree C between boiling in metallic and glass vessels (Gay-Lussac), and "superheating" up to 112 degrees C on extracting dissolved air out of water (De Luc). I have confirmed most of these observations in my own experiments, many of which are described in this paper. Water boils at the "boiling point" only under very particular circumstances. Our common-sense intuition about the fixedness of the boiling point is only sustained by our limited experience.

  18. Boiling point measurements on liquid UO2

    International Nuclear Information System (INIS)

    Bober, M.; Singer, J.; Trapp, M.

    1986-01-01

    In analogy to the classic boiling point method, a quasi-stationary millisecond laser-heating technique was applied to measure the saturated-vapour pressure curve of liquid UO 2 in the temperature range of 3500 to 4500 K. The result is represented by log p(MPa) 5.049 -23042/T(K) according to an average heat of vaporization of 441 kJ/mol and a normal boiling point of 3808 K. Besides, spectral emissivities of liquid UO 2 were measured at the pyrometer wavelengths of 752 and 1064 nm. (author)

  19. The boiling point of stratospheric aerosols.

    Science.gov (United States)

    Rosen, J. M.

    1971-01-01

    A photoelectric particle counter was used for the measurement of aerosol boiling points. The operational principle involves raising the temperature of the aerosol by vigorously heating a portion of the intake tube. At or above the boiling point, the particles disintegrate rather quickly, and a noticeable effect on the size distribution and concentration is observed. Stratospheric aerosols appear to have the same volatility as a solution of 75% sulfuric acid. Chemical analysis of the aerosols indicates that there are other substances present, but that the sulfate radical is apparently the major constituent.

  20. Microsoft SharePoint 2010 development cookbook

    CERN Document Server

    Musters, Ed

    2011-01-01

    The plan of the book is to build a relationship with the Author as your personal guide through the most common "pattern" of SharePoint development. In cookbook style, you will be led carefully step by step through a comprehensive set of recipes. The practical example starts quickly and builds logically throughout the chapters to create a common theme. You will be developing coding techniques that you will be able to apply to the real world. In fact, this book will train you for the first SharePoint development project you will join. This book is written for the ASP.NET developer who wants to g

  1. Dynamics and mission design near libration points

    CERN Document Server

    Gómez, G; Simo, C; Martínez, R

    2001-01-01

    In this book the problem of station keeping is studied for orbits near libration points in the solar system. The main focus is on orbits near halo ones in the (Earth+Moon)-Sun system. Taking as starting point the restricted three-body problem, the motion in the full solar system is considered as a perturbation of this simplified model. All the study is done with enough generality to allow easy application to other primary-secondary systems as a simple extension of the analytical and numerical computations. Contents: Bibliographical Survey; Halo Orbits. Analytical and Numerical Study; The Neigh

  2. Point defect relaxation volumes for copper

    International Nuclear Information System (INIS)

    Miller, K.M.

    1979-11-01

    The methods used for the determination of point defect relaxation volumes are discussed and it is shown that a previous interatomic potential derived for copper is inaccurate and results obtained using it are invalid. A new interatomic potential has been produced for copper and a computer simulation of point and planar defects carried out. A vacancy relaxation volume of -0.33 atomic volumes has been found with interstitial values in the range 1.7 to 2.0 atomic volumes. It is shown that these values in current theories of irradiation induced swelling lead to an anomalously high value for dislocation bias compared with that determined experimentally. (author)

  3. Point card compatible automatic vending machine for canned drink; Point card taio kan jido hanbaiki

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-01-10

    A point card compatible automatic vending machine for canned drinks is developed, which provides drink manufacturers with a powerful tool to acquire selling sites and attract consumers. Since the machine is equipped with a device to handle point cards, regular customers have increased and sales have picked up. A point card issuing device is also installed, and the new machine issues a point card whenever a customer wants. The drink manufacturers are evaluating high of the vending machine because it will contribute to the diffusion of the point card system and because a sales promotion campaign may be conducted through the vending machine for instance by exchanging a fully marked card with a giveaway on the spot. In the future, a bill validator (paper money identifier) will be integrated even with small size machines for the diffusion of point card compatible machines. (translated by NEDO)

  4. Quantitative structure-property relationships for prediction of boiling point, vapor pressure, and melting point.

    Science.gov (United States)

    Dearden, John C

    2003-08-01

    Boiling point, vapor pressure, and melting point are important physicochemical properties in the modeling of the distribution and fate of chemicals in the environment. However, such data often are not available, and therefore must be estimated. Over the years, many attempts have been made to calculate boiling points, vapor pressures, and melting points by using quantitative structure-property relationships, and this review examines and discusses the work published in this area, and concentrates particularly on recent studies. A number of software programs are commercially available for the calculation of boiling point, vapor pressure, and melting point, and these have been tested for their predictive ability with a test set of 100 organic chemicals.

  5. Obesity prevention at the point of purchase.

    Science.gov (United States)

    Cohen, D A; Lesser, L I

    2016-05-01

    The point of purchase is when people may make poor and impulsive decisions about what and how much to buy and consume. Because point of purchase strategies frequently work through non-cognitive processes, people are often unable to recognize and resist them. Because people lack insight into how marketing practices interfere with their ability to routinely eat healthy, balanced diets, public health entities should protect consumers from potentially harmful point of purchase strategies. We describe four point of purchase policy options including standardized portion sizes; standards for meals that are sold as a bundle, e.g. 'combo meals'; placement and marketing restrictions on highly processed low-nutrient foods; and explicit warning labels. Adoption of such policies could contribute significantly to the prevention of obesity and diet-related chronic diseases. We also discuss how the policies could be implemented, along with who might favour or oppose them. Many of the policies can be implemented locally, while preserving consumer choice. © 2016 World Obesity.

  6. ASIC For Complex Fixed-Point Arithmetic

    Science.gov (United States)

    Petilli, Stephen G.; Grimm, Michael J.; Olson, Erlend M.

    1995-01-01

    Application-specific integrated circuit (ASIC) performs 24-bit, fixed-point arithmetic operations on arrays of complex-valued input data. High-performance, wide-band arithmetic logic unit (ALU) designed for use in computing fast Fourier transforms (FFTs) and for performing ditigal filtering functions. Other applications include general computations involved in analysis of spectra and digital signal processing.

  7. OH masers associated with IRAS point sources

    NARCIS (Netherlands)

    Masheder, MRW; Cohen, RJ; Martin-Hernandez, NL; Migenes,; Reid, MJ

    2002-01-01

    We report a search for masers from the Lambda-doublet of the ground-state of OH at 18cm, carried out with the Jodrell Bank Lovell Telescope and with the 25m Dwingeloo telescope. All objects north of delta = -20degrees which appear in the IRAS Point Source Catalog with fluxes > 1000 Jy at 60mum and

  8. Some genus 3 curves with many points

    NARCIS (Netherlands)

    Auer, R; Top, J; Fieker, C; Kohel, DR

    2002-01-01

    We explain a naive approach towards the problem of finding genus 3 curves C over any given finite field F-q of odd characteristic, with a number of rational points close to the Hasse-Weil-Serre upper bound q+1+3[2rootq]. The method turns out to be successful at least in characteristic 3.

  9. Common Fixed Points for Weakly Compatible Maps

    Indian Academy of Sciences (India)

    The purpose of this paper is to prove a common fixed point theorem, from the class of compatible continuous maps to a larger class of maps having weakly compatible maps without appeal to continuity, which generalized the results of Jungck [3], Fisher [1], Kang and Kim [8], Jachymski [2], and Rhoades [9].

  10. Diagnosing patients at point of care

    CSIR Research Space (South Africa)

    Vilakazi, CB

    2015-10-01

    Full Text Available of pregnant women, the Cellnostics portable blood analyser and paper-based diagnostic solutions. Umbiflow is a Doppler ultrasound device that can determine at the primary point of care, such as a clinic, whether a fetus that is small for gestational age...

  11. Visibility of noisy point cloud data

    KAUST Repository

    Mehra, Ravish; Tripathi, Pushkar; Sheffer, Alla; Mitra, Niloy J.

    2010-01-01

    for the points set, visibility is computed based on a construction involving convex hull in a dual space, an idea inspired by the work of Katz et al. [26]. We derive theoretical bounds on the behavior of the method in the presence of noise and concavities

  12. Quench dynamics across quantum critical points

    International Nuclear Information System (INIS)

    Sengupta, K.; Powell, Stephen; Sachdev, Subir

    2004-01-01

    We study the quantum dynamics of a number of model systems as their coupling constants are changed rapidly across a quantum critical point. The primary motivation is provided by the recent experiments of Greiner et al. [Nature (London) 415, 39 (2002)] who studied the response of a Mott insulator of ultracold atoms in an optical lattice to a strong potential gradient. In a previous work, it had been argued that the resonant response observed at a critical potential gradient could be understood by proximity to an Ising quantum critical point describing the onset of density wave order. Here we obtain numerical results on the evolution of the density wave order as the potential gradient is scanned across the quantum critical point. This is supplemented by studies of the integrable quantum Ising spin chain in a transverse field, where we obtain exact results for the evolution of the Ising order correlations under a time-dependent transverse field. We also study the evolution of transverse superfluid order in the three-dimensional case. In all cases, the order parameter is best enhanced in the vicinity of the quantum critical point

  13. Detecting change-points in extremes

    KAUST Repository

    Dupuis, D. J.; Sun, Ying; Wang, Huixia Judy

    2015-01-01

    Even though most work on change-point estimation focuses on changes in the mean, changes in the variance or in the tail distribution can lead to more extreme events. In this paper, we develop a new method of detecting and estimating the change

  14. Modelling occupants’ heating set-point prefferences

    DEFF Research Database (Denmark)

    Andersen, Rune Vinther; Olesen, Bjarne W.; Toftum, Jørn

    2011-01-01

    consumption. Simultaneous measurement of the set-point of thermostatic radiator valves (trv), and indoor and outdoor environment characteristics was carried out in 15 dwellings in Denmark in 2008. Linear regression was used to infer a model of occupants’ interactions with trvs. This model could easily...... be implemented in most simulation software packages to increase the validity of the simulation outcomes....

  15. Kelp diagrams : Point set membership visualization

    NARCIS (Netherlands)

    Dinkla, K.; Kreveld, van M.J.; Speckmann, B.; Westenberg, M.A.

    2012-01-01

    We present Kelp Diagrams, a novel method to depict set relations over points, i.e., elements with predefined positions. Our method creates schematic drawings and has been designed to take aesthetic quality, efficiency, and effectiveness into account. This is achieved by a routing algorithm, which

  16. Lipoprotein lipase isoelectric point isoforms in humans

    DEFF Research Database (Denmark)

    Badia-Villanueva, M.; Carulla, P.; Carrascal, M.

    2014-01-01

    -heparin plasma (PHP), LPL consists of a pattern of more than 8 forms of the same apparent molecular weight, but different isoelectric point (pI). In the present study we describe, for the first time, the existence of at least nine LPL pI isoforms in human PHP, with apparent pI between 6.8 and 8.6. Separation...

  17. 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.

  18. The Tipping Point and the Adventure Advantage.

    Science.gov (United States)

    Prouty, Dick

    1998-01-01

    Insights from chaos theory--the interconnectedness of everything, nonlinear cause and effect, leverage and the "tipping point," and the importance of aligning interventions within a system--are applied to social action and illustrated via the role of adventure education in school and community interventions in the Brattleboro (Vermont) Leadership…

  19. Lane Determination with GPS Precise Point Positioning

    NARCIS (Netherlands)

    Knoop, V.L.; de Bakker, P.F.; Tiberius, C.C.J.M.; van Arem, B.

    2017-01-01

    Modern intelligent transport solutions can achieve an improvement of traffic flow on motorways. With lane-specific measurements and lane-specific control, more measures are possible. Single frequency precise point positioning (PPP) is a newly developed and affordable technique to achieve an

  20. PCX, Interior-Point Linear Programming Solver

    International Nuclear Information System (INIS)

    Czyzyk, J.

    2004-01-01

    1 - Description of program or function: PCX solves linear programming problems using the Mehrota predictor-corrector interior-point algorithm. PCX can be called as a subroutine or used in stand-alone mode, with data supplied from an MPS file. The software incorporates modules that can be used separately from the linear programming solver, including a pre-solve routine and data structure definitions. 2 - Methods: The Mehrota predictor-corrector method is a primal-dual interior-point method for linear programming. The starting point is determined from a modified least squares heuristic. Linear systems of equations are solved at each interior-point iteration via a sparse Cholesky algorithm native to the code. A pre-solver is incorporated in the code to eliminate inefficiencies in the user's formulation of the problem. 3 - Restriction on the complexity of the problem: There are no size limitations built into the program. The size of problem solved is limited by RAM and swap space on the user's computer