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  1. Pharmacometabolomic signature of ataxia SCA1 mouse model and lithium effects.

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    Bertrand Perroud

    Full Text Available We have shown that lithium treatment improves motor coordination in a spinocerebellar ataxia type 1 (SCA1 disease mouse model (Sca1(154Q/+. To learn more about disease pathogenesis and molecular contributions to the neuroprotective effects of lithium, we investigated metabolomic profiles of cerebellar tissue and plasma from SCA1-model treated and untreated mice. Metabolomic analyses of wild-type and Sca1(154Q/+ mice, with and without lithium treatment, were performed using gas chromatography time-of-flight mass spectrometry and BinBase mass spectral annotations. We detected 416 metabolites, of which 130 were identified. We observed specific metabolic perturbations in Sca1(154Q/+ mice and major effects of lithium on metabolism, centrally and peripherally. Compared to wild-type, Sca1(154Q/+ cerebella metabolic profile revealed changes in glucose, lipids, and metabolites of the tricarboxylic acid cycle and purines. Fewer metabolic differences were noted in Sca1(154Q/+ mouse plasma versus wild-type. In both genotypes, the major lithium responses in cerebellum involved energy metabolism, purines, unsaturated free fatty acids, and aromatic and sulphur-containing amino acids. The largest metabolic difference with lithium was a 10-fold increase in ascorbate levels in wild-type cerebella (p<0.002, with lower threonate levels, a major ascorbate catabolite. In contrast, Sca1(154Q/+ mice that received lithium showed no elevated cerebellar ascorbate levels. Our data emphasize that lithium regulates a variety of metabolic pathways, including purine, oxidative stress and energy production pathways. The purine metabolite level, reduced in the Sca1(154Q/+ mice and restored upon lithium treatment, might relate to lithium neuroprotective properties.

  2. NELL-1 induces Sca-1+ mesenchymal progenitor cell expansion in models of bone maintenance and repair.

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    James, Aaron W; Shen, Jia; Tsuei, Rebecca; Nguyen, Alan; Khadarian, Kevork; Meyers, Carolyn A; Pan, Hsin Chuan; Li, Weiming; Kwak, Jin H; Asatrian, Greg; Culiat, Cymbeline T; Lee, Min; Ting, Kang; Zhang, Xinli; Soo, Chia

    2017-06-15

    NELL-1 is a secreted, osteogenic protein first discovered to control ossification of the cranial skeleton. Recently, NELL-1 has been implicated in bone maintenance. However, the cellular determinants of NELL-1's bone-forming effects are still unknown. Here, recombinant human NELL-1 (rhNELL-1) implantation was examined in a clinically relevant nonhuman primate lumbar spinal fusion model. Prolonged rhNELL-1 protein release was achieved using an apatite-coated β-tricalcium phosphate carrier, resulting in a local influx of stem cell antigen-1-positive (Sca-1+) mesenchymal progenitor cells (MPCs), and complete osseous fusion across all samples (100% spinal fusion rate). Murine studies revealed that Nell-1 haploinsufficiency results in marked reductions in the numbers of Sca-1+CD45-CD31- bone marrow MPCs associated with low bone mass. Conversely, rhNELL-1 systemic administration in mice showed a marked anabolic effect accompanied by increased numbers of Sca-1+CD45-CD31- bone marrow MPCs. Mechanistically, rhNELL-1 induces Sca-1 transcription among MPCs, in a process requiring intact Wnt/β-catenin signaling. In summary, NELL-1 effectively induces bone formation across small and large animal models either via local implantation or intravenous delivery. NELL-1 induces an expansion of a bone marrow subset of MPCs with Sca-1 expression. These findings provide compelling justification for the clinical translation of a NELL-1-based therapy for local or systemic bone formation.

  3. SCA28

    DEFF Research Database (Denmark)

    Svenstrup, Kirsten; Nielsen, Troels Tolstrup; Aidt, Frederik

    2017-01-01

    The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene...... AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico...

  4. Sca13.

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    Waters, M F; Pulst, S M

    2008-01-01

    Spinocerebellar ataxia 13 (SCA13), initially described in a four-generation French family, has now also been characterized in a large Filipino pedigree. Ongoing investigations continue to identify additional SCA13 families and individuals. Recently, studies have shown that mutations in the voltage-gated potassium channel KCNC3 are causative for SCA13. Sequence analysis of KCNC3 revealed mutations 1554G-->A (R420H) in the Filipino and 1639C-->A (F448L) in the French pedigrees. Both mutations alter KCNC3 function in a Xenopus laevis oocyte expression system. KCNC3(R420H), located in the voltage sensor of the channel, has no detectable channel activity when expressed alone, and strong dominant negative effects when coexpressed with wild-type KCNC3. KCNC3(F448L) shifts the activation curve in the negative direction and causes an approximately sevenfold slowing of channel closure. These mutations are expected to change the output characteristics of fast-spiking cerebellar neurons, where KCNC channels confer capacity for high-frequency repetitive firing.

  5. Sudden Cardiac Arrest (SCA)

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    ... Arrest (SCA) Back to Heart Diseases & Disorders Sudden Cardiac Arrest (SCA) Sudden Cardiac Arrest ( SCA ) occurs when the heart stops beating, abruptly ... to saving someone who is having a sudden cardiac arrest , it is important to understand the difference. The ...

  6. Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model.

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    Mimi Cushman-Nick

    Full Text Available There are no effective therapeutics that antagonize or reverse the protein-misfolding events underpinning polyglutamine (PolyQ disorders, including Spinocerebellar Ataxia Type-3 (SCA3. Here, we augment the proteostasis network of Drosophila SCA3 models with Hsp104, a powerful protein disaggregase from yeast, which is bafflingly absent from metazoa. Hsp104 suppressed eye degeneration caused by a C-terminal ataxin-3 (MJD fragment containing the pathogenic expanded PolyQ tract, but unexpectedly enhanced aggregation and toxicity of full-length pathogenic MJD. Hsp104 suppressed toxicity of MJD variants lacking a portion of the N-terminal deubiquitylase domain and full-length MJD variants unable to engage polyubiquitin, indicating that MJD-ubiquitin interactions hinder protective Hsp104 modalities. Importantly, in staging experiments, Hsp104 suppressed toxicity of a C-terminal MJD fragment when expressed after the onset of PolyQ-induced degeneration, whereas Hsp70 was ineffective. Thus, we establish the first disaggregase or chaperone treatment administered after the onset of pathogenic protein-induced degeneration that mitigates disease progression.

  7. Sudden Cardiac Arrest (SCA) Risk Assessment

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    ... Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without warning, and two- ... and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool is supported in part ...

  8. Deactivation of TBP contributes to SCA17 pathogenesis.

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    Hsu, Tun-Chieh; Wang, Cheng-Kuang; Yang, Chun-Yen; Lee, Li-Ching; Hsieh-Li, Hsiu-Mei; Ro, Long-Sun; Chen, Chiung-Mei; Lee-Chen, Guey-Jen; Su, Ming-Tsan

    2014-12-20

    Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). Previous studies have shown that polyQ-expanded TBP forms neurotoxic aggregates and alters downstream genes. However, how expanded polyQ tracts affect the function of TBP and the link between dysfunctional TBP and SCA17 is not clearly understood. In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. In addition to forming neurotoxic aggregates, we determined that polyQ-expanded TBP reduces its own intrinsic DNA-binding and transcription abilities. Dysfunctional TBP also disrupts normal TBP function. Furthermore, heterozygous dTbp amorph mutant flies exhibited SCA17-like phenotypes and flies expressing polyQ-expanded TBP exhibited enhanced retinal degeneration, suggesting that loss of TBP function may contribute to SCA17 pathogenesis. We further determined that the downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Motor neuron degeneration correlates with respiratory dysfunction in SCA1.

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    Orengo, James P; van der Heijden, Meike E; Hao, Shuang; Tang, Jianrong; Orr, Harry T; Zoghbi, Huda Y

    2018-01-29

    Spinocerebellar ataxia type 1 (SCA1) is characterized by adult-onset cerebellar degeneration with attendant loss of motor coordination. Bulbar function is eventually impaired, and patients tend to die from inability to clear the airway. We asked whether motor neuron degeneration is at the root of bulbar dysfunction by studying SCA1 knock-in mice. We analyzed spinal cord and brainstem motor neurons in SCA1 knock-in (Atxn1 154Q ) mice at 1, 3, and 6 months of age. Specifically, we assessed breathing physiology, diaphragm histology and electromyography, and motor neuron histology and immunohistochemistry. Atxn1 154Q mice show progressive neuromuscular respiratory abnormalities, neurogenic changes in diaphragm, and motor neuron degeneration in the spinal cord and brainstem. The latter is accompanied by reactive astrocytosis and accumulation of Atxn1 aggregates in the motor neuron nuclei. This dovetails with previous observations in SCA1 patient tissue. Atxn1 154Q mice develop bulbar dysfunction because of motor neuron degeneration. These findings confirm the Atxn1 154Q line as a SCA1 model with face and construct validity for this understudied disease feature. Furthermore, this model is suitable to study the pathogenic mechanism driving motor neuron degeneration in SCA1 and perhaps other degenerative motor neuron diseases. From a clinical standpoint, the data indicate that pulmonary function testing and employment of non-invasive ventilator support could be beneficial in SCA1 patients. The physiological tests used in this study may serve as valuable biomarkers for future therapeutic interventions and clinical trials. © 2018. Published by The Company of Biologists Ltd.

  10. Pathoanatomy of cerebellar degeneration in spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3).

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    Scherzed, W; Brunt, E R; Heinsen, H; de Vos, R A; Seidel, K; Bürk, K; Schöls, L; Auburger, G; Del Turco, D; Deller, T; Korf, H W; den Dunnen, W F; Rüb, U

    2012-09-01

    The cerebellum is one of the well-known targets of the pathological processes underlying spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Despite its pivotal role for the clinical pictures of these polyglutamine ataxias, no pathoanatomical studies of serial tissue sections through the cerebellum have been performed in SCA2 and SCA3 so far. Detailed pathoanatomical data are an important prerequisite for the identification of the initial events of the underlying disease processes of SCA2 and SCA3 and the reconstruction of its spread through the brain. In the present study, we performed a pathoanatomical investigation of serial thick tissue sections through the cerebellum of clinically diagnosed and genetically confirmed SCA2 and SCA3 patients. This study demonstrates that the cerebellar Purkinje cell layer and all four deep cerebellar nuclei consistently undergo considerable neuronal loss in SCA2 and SCA3. These cerebellar findings contribute substantially to the pathogenesis of clinical symptoms (i.e., dysarthria, intention tremor, oculomotor dysfunctions) of SCA2 and SCA3 patients and may facilitate the identification of the initial pathological alterations of the pathological processes of SCA2 and SCA3 and reconstruction of its spread through the brain.

  11. Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

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    Kung PJ

    2014-10-01

    Full Text Available Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17, the expansion of a translated CAG repeat in the TATA box binding protein (TBP gene results in a long polyglutamine (polyQ tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

  12. Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model.

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    Ferro, Austin; Carbone, Emily; Zhang, Jenny; Marzouk, Evan; Villegas, Monica; Siegel, Asher; Nguyen, Donna; Possidente, Thomas; Hartman, Jessilyn; Polley, Kailen; Ingram, Melissa A; Berry, Georgia; Reynolds, Thomas H; Possidente, Bernard; Frederick, Kimberley; Ives, Stephen; Lagalwar, Sarita

    2017-01-01

    Mitochondrial dysfunction plays a significant role in neurodegenerative disease including ataxias and other movement disorders, particularly those marked by progressive degeneration in the cerebellum. In this study, we investigate the role of mitochondrial oxidative phosphorylation (OXPHOS) deficits in cerebellar tissue of a Purkinje cell-driven spinocerebellar ataxia type 1 (SCA1) mouse. Using RNA sequencing transcriptomics, OXPHOS complex assembly analysis and oxygen consumption assays, we report that in the presence of mutant polyglutamine-expanded ataxin-1, SCA1 mice display deficits in cerebellar OXPHOS complex I (NADH-coenzyme Q oxidoreductase). Complex I genes are upregulated at the time of symptom onset and upregulation persists into late stage disease; yet, functional assembly of complex I macromolecules are diminished and oxygen respiration through complex I is reduced. Acute treatment of postsymptomatic SCA1 mice with succinic acid, a complex II (succinate dehydrogenase) electron donor to bypass complex I dysfunction, ameliorated cerebellar OXPHOS dysfunction, reduced cerebellar pathology and improved motor behavior. Thus, exploration of mitochondrial dysfunction and its role in neurodegenerative ataxias, and warrants further investigation.

  13. Design and Testing of Space Telemetry SCA Waveform

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    Mortensen, Dale J.; Handler, Louis M.; Quinn, Todd M.

    2006-01-01

    A Software Communications Architecture (SCA) Waveform for space telemetry is being developed at the NASA Glenn Research Center (GRC). The space telemetry waveform is implemented in a laboratory testbed consisting of general purpose processors, field programmable gate arrays (FPGAs), analog-to-digital converters (ADCs), and digital-to-analog converters (DACs). The radio hardware is integrated with an SCA Core Framework and other software development tools. The waveform design is described from both the bottom-up signal processing and top-down software component perspectives. Simulations and model-based design techniques used for signal processing subsystems are presented. Testing with legacy hardware-based modems verifies proper design implementation and dynamic waveform operations. The waveform development is part of an effort by NASA to define an open architecture for space based reconfigurable transceivers. Use of the SCA as a reference has increased understanding of software defined radio architectures. However, since space requirements put a premium on size, mass, and power, the SCA may be impractical for today s space ready technology. Specific requirements for an SCA waveform and other lessons learned from this development are discussed.

  14. Involvement of the auditory brainstem system in spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7)

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    Hoche, F.; Seidel, K.; Brunt, E. R.; Auburger, G.; Schoels, L.; Buerk, K.; de Vos, R. A.; den Dunnen, W.; Bechmann, I.; Egensperger, R.; Van Broeckhoven, C.; Gierga, K.; Deller, T.; Rueb, U.

    2008-01-01

    Aims: The spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7) are clinically characterized by progressive and severe ataxic symptoms, dysarthria, dysphagia, oculomotor impairments, pyramidal and extrapyramidal manifestations and sensory deficits. Although recent clinical studies

  15. Evaluation of SCaMPR Satellite QPEs for Operational Hydrologic Prediction

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    LEE, H.; Zhang, Y.; Seo, D.; Kitzmiller, D. H.; Kuligowski, R. J.; Corby, R.

    2011-12-01

    National Weather Service (NWS) River Forecast Centers (RFCs) use rain gauge or radar-gauge multi-sensor quantitative precipitation estimates (QPEs) as the primary rainfall input to their operational hydrologic models. In areas with poor radar and rain gauge coverage, satellite-based QPEs are a potential alternative. In this work, we evaluated the utility of satellite-based QPEs produced via the Self-Calibrating Multivariate Precipitation Retrieval (SCaMPR) algorithm for operational hydrologic modeling for a set of basins in Texas and Louisiana for the period of 2000-7. First, we assessed the relative accuracy of two sets of SCaMPR QPEs versus gauge-only QPE, with operational multi-sensor QPEs as the reference. One set used only operational polar orbiting satellite microwave input as the predictors, the other included Tropical Rainfall Measuring Mission (TRMM) rain rates in the calibration process. We then performed hydrologic simulations using these QPEs and evaluated the simulations. Results indicated that a) SCaMPR QPEs showed better/worse skill than the gauge-only QPEs in resolving heavy precipitation at 1-h/24-h time intervals in terms of Critical Success Index (CSI); b) SCaMPR QPEs underperformed gauge-only QPEs in simulating flood events; and c) ingesting TRMM rainfall rates helped enhance the hydrologic utility of SCaMPR QPE, by mitigating the positive bias of SCaMPR QPEs, elevating the detection rates of heavy rainfall, and improving the simulation of flood discharge. Our findings suggest that the superior performance of gauge-only QPEs versus SCaMPR in hydrologic simulations is tied to its better accuracy at 24-h scale. The implication of the scale dependence in the relative performance of SCaMPR QPEs to their potential hydrologic utility is discussed.

  16. Ancestral origin of the ATTCT repeat expansion in spinocerebellar ataxia type 10 (SCA10.

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    Teresa Almeida

    Full Text Available Spinocerebellar ataxia type 10 (SCA10 is an autosomal dominant neurodegenerative disease characterized by cerebellar ataxia and seizures. The disease is caused by a large ATTCT repeat expansion in the ATXN10 gene. The first families reported with SCA10 were of Mexican origin, but the disease was soon after described in Brazilian families of mixed Portuguese and Amerindian ancestry. The origin of the SCA10 expansion and a possible founder effect that would account for its geographical distribution have been the source of speculation over the last years. To unravel the mutational origin and spread of the SCA10 expansion, we performed an extensive haplotype study, using closely linked STR markers and intragenic SNPs, in families from Brazil and Mexico. Our results showed (1 a shared disease haplotype for all Brazilian and one of the Mexican families, and (2 closely-related haplotypes for the additional SCA10 Mexican families; (3 little or null genetic distance in small normal alleles of different repeat sizes, from the same SNP lineage, indicating that they are being originated by a single step mechanism; and (4 a shared haplotype for pure and interrupted expanded alleles, pointing to a gene conversion model for its generation. In conclusion, we show evidence for an ancestral common origin for SCA10 in Latin America, which might have arisen in an ancestral Amerindian population and later have been spread into the mixed populations of Mexico and Brazil.

  17. Gene, Stem Cell, and Alternative Therapies for SCA 1

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    Jacob Lewis Wagner

    2016-08-01

    Full Text Available Spinocerebellar ataxia 1 is an autosomal dominant disease characterized by neurodegeneration and motor dysfunction. In disease pathogenesis, polyglutamine expansion within Ataxin-1, a gene involved in transcriptional repression, causes protein nuclear inclusions to form. Most notably, neuronal dysfunction presents in Purkinje cells. However, the effect of mutant Ataxin-1 is not entirely understood. Two mouse models are employed to represent spinocerebellar ataxia 1, a B05 transgenic model that specifically expresses mutant Ataxin-1 in Purkinje cells, and a Sca1 154Q/2Q model that inserts the polyglutamine expansion into the mouse Ataxin-1 locus so that the mutant Ataxin-1 is expressed in all cells that express Ataxin-1. This review aims to summarize and evaluate the wide variety of therapies proposed for spinocerebellar ataxia 1, specifically gene and stem cell therapies.

  18. Neuropsychological Features of Patients with Spinocerebellar Ataxia (SCA) Types 1, 2, 3, and 6

    NARCIS (Netherlands)

    Klinke, I.A.; Minnerop, M.; Schmitz-Hubsch, T.; Hendriks, M.P.H.; Klockgether, T.; Wüllner, U.; Helmstaedter, C.

    2010-01-01

    A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic and

  19. Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA in a large group of Brazilian patients Freqüência das mutações que causam ataxia espinocerebelar (SCA1, SCA2, MJD/SCA3 e DRPLA em um grupo numeroso de pacientes Brasileiros

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    Iscia Lopes-Cendesi

    1997-09-01

    Full Text Available Spinocerebellar ataxia type 1 (SCA1, spinocerebellar ataxia type 2 (SCA2 and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3 are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%, 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6 % in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30 % of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.Ataxia espinocerebelar tipo 1 (SCA1, ataxia espinocerebelar tipo 2 (SCA2 e doença de Machado-Joseph ou ataxia espinocerebelar tipo 3 (MJD/SCA3 são três formas de ataxia espinocerebelar (SCA que apresentam herança genética autossômica dominante. Nessas três doenças foi encontrada uma expansão instável de trinucleotídeo CAG localizada na região codificadora dos

  20. SCA8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to SCA8 pathology.

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    Chen, Wei-Lun; Lin, Jun-Wei; Huang, Hei-Jen; Wang, Su-Min; Su, Ming-Tsan; Lee-Chen, Guey-Jen; Chen, Chiung-Mei; Hsieh-Li, Hsiu Mei

    2008-10-03

    An increasing number of inherited neurodegenerative diseases are known to be caused by the expansion of unstable trinucleotide repeat tracts. Spinocerebellar ataxia type 8 (SCA8) has been identified as being partly caused by a CTG expansion in an untranslated, endogenous antisense RNA that overlaps the Kelch-like 1 (KLHL1) gene. Clinically, SCA8 patients show similar features to those with the other SCAs, including limb and truncal ataxia, ataxic dysarthria and horizontal nystagmus, all of which are signs of dysfunction of the cerebellar system. However, allele sizes within the SCA8 proposed pathogenic range have been reported in patients with ataxia of unknown etiology, in individuals from pedigrees with other SCA or Friedreich's ataxia, and in patients with Alzheimer's disease, schizophrenia or parkinsonism. These observations suggest that mutation of the SCA8 locus might affect neurons other than the cerebellum. Antisense transcripts are known to regulate complementary sense transcripts and are involved in several biologic functions, such as development, adaptive response, and viral infection. In order to test whether SCA8 affects the KLHL1 expression by antisense RNA in brain cells, we examined the expression pattern of KLHL1 and SCA8 in human tissues and in mouse brain regions. SCA8 expression was colocalized with KLHL1 transcript in many brain regions whose functions are correlated to the clinical symptoms of SCA8 patients. These findings lead to the hypothesis of a possible relevance that SCA8 transcript downregulates KLHL1 expression through an antisense mechanism, which then leads to SCA8 neuropathogenesis.

  1. JTRS/SCA and Custom/SDR Waveform Comparison

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    Oldham, Daniel R.; Scardelletti, Maximilian C.

    2007-01-01

    This paper compares two waveform implementations generating the same RF signal using the same SDR development system. Both waveforms implement a satellite modem using QPSK modulation at 1M BPS data rates with one half rate convolutional encoding. Both waveforms are partitioned the same across the general purpose processor (GPP) and the field programmable gate array (FPGA). Both waveforms implement the same equivalent set of radio functions on the GPP and FPGA. The GPP implements the majority of the radio functions and the FPGA implements the final digital RF modulator stage. One waveform is implemented directly on the SDR development system and the second waveform is implemented using the JTRS/SCA model. This paper contrasts the amount of resources to implement both waveforms and demonstrates the importance of waveform partitioning across the SDR development system.

  2. Augmenting the SCaN Link Budget Tool with Validated Atmospheric Propagation

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    Steinkerchner, Leo; Welch, Bryan

    2017-01-01

    In any Earth-Space or Space-Earth communications link, atmospheric effects cause significant signal attenuation. In order to develop a communications system that is cost effective while meeting appropriate performance requirements, it is important to accurately predict these effects for the given link parameters. This project aimed to develop a Matlab(TradeMark) (The MathWorks, Inc.) program that could augment the existing Space Communications and Navigation (SCaN) Link Budget Tool with accurate predictions of atmospheric attenuation of both optical and radio-frequency signals according to the SCaN Optical Link Assessment Model Version 5 and the International Telecommunications Union, Radiocommunications Sector (ITU-R) atmospheric propagation loss model, respectively. When compared to data collected from the Advance Communications Technology Satellite (ACTS), the radio-frequency model predicted attenuation to within 1.3 dB of loss for 95 of measurements. Ultimately, this tool will be integrated into the SCaN Center for Engineering, Networks, Integration, and Communications (SCENIC) user interface in order to support analysis of existing SCaN systems and planning capabilities for future NASA missions.

  3. Stable phenotype and function of immortalized Lin-Sca-1+ cardiac progenitor cells in long-term culture: a step closer to standardization.

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    Freire, Ana G; Nascimento, Diana S; Forte, Giancarlo; Valente, Mariana; Resende, Tatiana P; Pagliari, Stefania; Abreu, Cláudia; Carvalho, Isabel; Di Nardo, Paolo; Pinto-do-Ó, Perpétua

    2014-05-01

    Putative cardiac progenitor cells (CPCs) have been identified in the myocardium and are regarded as promising candidates for cardiac cell-based therapies. Although two distinct populations of CPCs reached the clinical setting, more detailed studies are required to portray the optimal cell type and therapeutic setting to drive robust cell engraftment and cardiomyogenesis after injury. Owing to the scarcity of the CPCs and the need for reproducibility, the generation of faithful cellular models would facilitate this scrutiny. Here, we evaluate whether immortalized Lin(-)Sca-1(+) CPCs (iCPC(Sca-1)) represent their native-cell counterpart, thereby constituting a robust in vitro model system for standardized investigation in the cardiac field. iCPC(Sca-1) were established in vitro as plastic adherent cells endowed with robust self-renewal capacity while preserving a stable phenotype in long-term culture. iCPC(Sca-1) differentiated into cardiomyocytic-, endothelial-, and smooth muscle-like cells when subjected to appropriate stimuli. The cell line consistently displayed features of Lin(-)Sca-1(+) CPCs in vitro, as well as in vivo after intramyocardial delivery in the onset of myocardial infarction (MI). Transplanted iCPC(Sca-1) significantly attenuated the functional and anatomical alterations caused by MI while promoting neovascularization. iCPC(Sca-1) are further shown to engraft, establish functional connections, and differentiate in loco into cardiomyocyte- and vasculature-like cells. These data validate iCPC(Sca-1) as an in vitro model system for Lin(-)Sca-1(+) progenitors and for systematic dissection of mechanisms underlying CPC subsets engraftment/differentiation in vivo. Moreover, iCPC(Sca-1) can be regarded as a ready-to-use CPCs source for pre-clinical bioengineering studies toward the development of novel strategies for restoration of the damaged myocardium.

  4. Differential recruitment of UBQLN2 to nuclear inclusions in the polyglutamine diseases HD and SCA3.

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    Zeng, Li; Wang, Bo; Merillat, Sean A; N Minakawa, Eiko; Perkins, Matthew D; Ramani, Biswarathan; Tallaksen-Greene, Sara J; Costa, Maria do Carmo; Albin, Roger L; Paulson, Henry L

    2015-10-01

    Accumulation of mutant polyglutamine proteins in intraneuronal inclusions is a hallmark of polyglutamine diseases. Impairment of protein clearance systems and sequestration of clearance-related proteins into inclusions occur in many protein folding diseases, including polyglutamine diseases. The ubiquitin-binding and proteasome adaptor protein UBQLN2 participates in protein homeostasis and localizes to inclusions in various neurodegenerative diseases. Employing mouse models and human brain tissue of Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3), we show that UBQLN2 is selectively recruited to inclusions in HD but not SCA3. Consistent with this result, in a cell-based system mutant HTT interacts with UBQLN2 through the UBA domain while the SCA3 disease protein ATXN3, a deubiquitinating enzyme, does not interact with UBQLN2. Differential recruitment of UBQLN2 to aggregates in HD and SCA3 underscores the heterogeneity of inclusions in polyglutamine diseases and suggests that components of neuronal protein quality control may be differentially perturbed in distinct polyQ diseases. Copyright © 2015. Published by Elsevier Inc.

  5. Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells.

    Science.gov (United States)

    Tanaka, Tomohiro; Obana, Masanori; Mohri, Tomomi; Ebara, Masaki; Otani, Yuta; Maeda, Makiko; Fujio, Yasushi

    2015-10-01

    Cytokines play important roles in cardiac repair and regeneration. Recently, we demonstrated that interleukin (IL)-6 family cytokines induce the endothelial differentiation of Sca-1+ cardiac resident stem cells through STAT3/Pim-1 signaling pathway. In contrast, the biological functions of IL-12 family cytokines in heart remain to be elucidated, though they show structural homology with IL-6. In the present study, we examined the effects of IL-12 family cytokines on the transdifferentiation of cardiac Sca-1+ cells into cardiac cells. RT-PCR analyses revealed that IL-27 receptor α (IL-27Rα), but not IL-12R or IL-23R, was expressed in cardiac Sca-1+ cells. The transcript expression of IL-27 was elevated in murine hearts in cardiac injury models. Intriguingly, IL-27 stimulation for 14 days induced the endothelial cell (EC) marker genes, such as CD-31 and VE-cadherin. Immunoblot analyses clarified that IL-27 treatment rapidly phosphorylated STAT3. IL-27 upregulated the expression of Pim-1, but the overexpression of dominant negative STAT3 abrogated the induction of Pim-1 by IL-27. Finally, adenoviral transfection of dominant negative Pim-1 inhibited IL-27-induced EC differentiation of cardiac Sca-1+ cells. These findings demonstrated that IL-27 promoted the commitment of cardiac stem cells into the EC lineage, possibly leading to neovascularization as a novel biological function. IL-27 could not only regulate the inflammation but also contribute to the maintenance of the tissue homeostasis through stem cell differentiation at inflammatory sites. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Training volunteers as conversation partners using "Supported Conversation for Adults with Aphasia" (SCA): a controlled trial.

    Science.gov (United States)

    Kagan, A; Black, S E; Duchan, F J; Simmons-Mackie, N; Square, P

    2001-06-01

    This article reports the development and evaluation of a new intervention termed "Supported Conversation for Adults with Aphasia" (SCA). The approach is based on the idea that the inherent competence of people with aphasia can be revealed through the skill of a conversation partner. The intervention approach was developed at a community-based aphasia center where volunteers interact with individuals with chronic aphasia and their families. The experimental study was designed to test whether training improves the conversational skills of volunteers, and, if so, whether the improvements affect the communication of their conversation partners with aphasia. Twenty volunteers received SCA training, and 20 control volunteers were merely exposed to people with aphasia. Comparisons between the groups' scores on a Measure of Supported Conversation for Adults with Aphasia provide support for the efficacy of SCA. Trained volunteers scored significantly higher than untrained volunteers on ratings of acknowledging competence [F(1, 36) = 19. 1, p aphasia. The training also produced a positive change in ratings of social [F(1, 36) = 5.7, p aphasia, even though these individuals did not participate in the training. Implications for the treatment of aphasia and an argument for a social model of intervention are discussed.

  7. Developing an Orographic Adjustment for the SCaMPR Algorithm

    Science.gov (United States)

    Yucel, I.; Akcelik, M.; Kuligowski, R. J.

    2016-12-01

    In support of the National Oceanic and Atmospheric Administration (NOAA) National Weather Service's (NWS) flash flood warning and heavy precipitation forecast efforts, the NOAA National Environmental Satellite Data and Information Service (NESDIS) Center for Satellite Applications and Research (STAR) has been providing satellite-based precipitation estimates operationally since 1978. The GOES-R Algorithm Working Group (AWG) is responsible for developing and demonstrating algorithms for retrieving various geophysical parameters from GOES data, including rainfall. The rainfall algorithm selected by the GOES-R AWG is the Self-Calibrating Multivariate Precipitation Retrieval (SCaMPR). However, the SCaMPR does not currently make any adjustments for the effects of complex topography on rainfall. Elevation-dependent bias structures suggest that there is an increased sensitivity to deep convection, which generates heavy precipitation at the expense of missing lighter precipitation events. A regionally dependent empirical elevation-based bias correction technique may help improve the quality of satellite-derived precipitation products. This study investigates the potential for improving the SCaMPR algorithm by incorporating an orographic correction based on calibration of the SCaMPR against rain gauge transects in northwestern Mexico to identify correctable biases related to elevation, slope, and wind direction. The findings suggest that continued improvement to the developed orographic correction scheme is warranted in order to advance quantitative precipitation estimation in complex terrain regions for use in weather forecasting and hydrologic applications. The relationships that are isolated during this analysis will be used to create a more accurate terrain adjustment for SCaMPR.

  8. Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38).

    Science.gov (United States)

    Borroni, Barbara; Di Gregorio, Eleonora; Orsi, Laura; Vaula, Giovanna; Costanzi, Chiara; Tempia, Filippo; Mitro, Nico; Caruso, Donatella; Manes, Marta; Pinessi, Lorenzo; Padovani, Alessandro; Brusco, Alfredo; Boccone, Loredana

    2016-07-01

    SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified. The present study was aimed at describing the clinical and neuroimaging features, and the natural history of SCA38. We extended our clinical and brain neuroimaging data on SCA38 including 21 cases from three Italian families. All had the ELOVL5 c.689G > T (p.Gly230Val) missense mutation. Age at disease onset was in the fourth decade of life. The presenting features were nystagmus (100% of cases) and slowly progressive gait ataxia (95%). Frequent signs and symptoms included pes cavus (82%) and hyposmia (76%); rarer symptoms were hearing loss (33%) and anxiety disorder (33%). The disease progressed with cerebellar symptoms such as limb ataxia, dysarthria, dysphagia, and ophtalmoparesis followed in the later stages by ophtalmoplegia. Peripheral nervous system involvement was present in the last phase of disease with sensory loss. Dementia or extrapyramidal signs were not detected. Significant loss of abilities of daily living was reported only after 20 years of the disease. Brain imaging documented cerebellar atrophy with sparing of cerebral cortex and no white matter disease. SCA38 is a rare form of inherited ataxia with characteristic clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. High relative frequency of SCA1 in Poland reflecting a potential founder effect.

    Science.gov (United States)

    Krysa, Wioletta; Sulek, Anna; Rakowicz, Maria; Szirkowiec, Walentyna; Zaremba, Jacek

    2016-08-01

    Spinocerebellar ataxias (SCAs) have irregular distributions worldwide. SCA1 is the most frequent in Poland, and no cases of SCA3 of Polish origin has yet been identified. In view of such patterns of SCAs occurrence, the relative frequency, geographical distribution and a possible founder effect of SCA1 were investigated. DNA samples of 134 probands with SCA1 and 228 controls were analysed. The genotyping of four markers, D6S89, D6S109, D6S274, D6S288, around the ATXN1 gene (SCA1) and sequencing of the selected variant of D6S89 were performed. The relative frequency of SCA1 was 68 %. The studied SCA1 pedigrees were irregularly distributed, with the highest concentration in Central Poland. Haplotyping revealed the association of ATXN1 gene mutation with a 197-bp variant of D6S89 marker (63 % of probands) and with a 184-bp variant of DS6274 (50.7 % of probands). Out of 61 SCA1 probands from Mazowieckie, 41 carried the same 197-bp variant. SCA1 relative frequency in Poland shows the highest value compared with the data from other countries worldwide. Due to the association with the mutation obtained for the investigated markers and the SCA1 pedigrees concentration in Central Poland, we hypothesise that it represents a potential founder effect.

  10. SOA for the Business Developer Concepts, BPEL, and SCA

    CERN Document Server

    Margolis, Ben

    2007-01-01

    Service-Oriented Architecture (SOA) is a way of organizing software. If your company's development projects adhere to the principles of SOA, the outcome will be an inventory of modular units called "services," which allow for a quick response to change. This book tells the SOA story in a simple, straightforward manner that will help you understand not only the buzzwords and benefits, but also the technologies that underlie SOA: XML, WSDL, SOAP, XPath, BPEL, SCA, and SDO. And through it all, the authors provide business examples and illustrations, giving a practical meaning to abstract ideas

  11. Spinocerebellar ataxia type 13 is an uncommon SCA subtype in the Chinese Han population.

    Science.gov (United States)

    Peng, Lan; Wang, Chunrong; Chen, Zhao; Wang, Jun-Ling; Tang, Bei-Sha; Jiang, Hong

    2013-07-01

    The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders, among which SCA subtype 13 (SCA13) was found associated with mutations in the KCNC3 gene. Among 522 Chinese Han SCA patients (including familial and sporadic) we have collected since 1995, approximately 40% of them have not yet been assigned genotype. To investigate the mutation frequency of KCNC3 in SCA patients from mainland Chinese Han population, we analyzed the KCNC3 gene in 201 unrelated patients diagnosed with dominantly inherited cerebellar ataxia using the denaturing high-performance liquid chromatography (DHPLC) method. All analyzed samples displayed the normal elution profile, which denoted that no disease-related mutation was identified, suggesting that SCA13 be a rare form of SCA in mainland China.

  12. Adsorption Behavior and Mechanism of SCA-1 on a Calcite Surface: A Molecular Dynamics Study.

    Science.gov (United States)

    Xue, Zhengyang; Shen, Qiying; Liang, Lijun; Shen, Jia-Wei; Wang, Qi

    2017-10-24

    The crystallization mechanism for natural mineral, especially the role of biological molecules in biomineralization, is still under debate. Protein adsorption on material surfaces plays a key role in biomineralization. In this article, molecular dynamics (MD) simulations were performed to systematically investigate the adsorption behavior of struthio camelus eggshell protein struthiocalcin-1 (SCA-1) on the calcite (104) surface with several different starting orientations in an explicit water environment. For each binding configuration, detailed adsorption behaviors and a mechanism were presented with the analysis of interaction energy, binding residues, hydrogen bonding, and structures (such as DSSP, dipole moment, and the electrostatic potential calculation). The results indicate that the positively charged and polar residues are the dominant residues for protein adsorption on the calcite (104) surface, and the strong electrostatic interaction drives the binding of model protein to the surface. The hydrogen bond bridge was found to play an important role in surface interactions as well. These results also demonstrate that SCA-1 is relatively rigid in spite of strong adsorption with few structural changes in α-helix and β-sheet contents. The results of the orientation calculation suggest that the dipole moment of the protein tends to remain parallel to calcite in most stable cases, which was confirmed by electrostatic potential isosurfaces analysis.

  13. Differentiation-Associated MicroRNA Alterations in Mouse Heart-Derived Sca-1+CD31− and Sca-1+CD31+ Cells

    Directory of Open Access Journals (Sweden)

    Qiong Wu

    2016-01-01

    Full Text Available Cardiac resident stem/progenitor cells (CSC/CPCs are critical to the cellular and functional integrity of the heart because they maintain myocardial cell homeostasis. Several populations of CSC/CPCs have been identified based on expression of different stem cell-associated antigens. Sca-1+ cells in the cardiac tissue may be the most common CSC/CPCs. However, they are a heterogeneous cell population and, in transplants, clinicians might transplant more endothelial cells, cardiomyocytes, or other cells than stem cells. The purposes of this study were to (1 isolate CSC/CPCs with Lin−CD45−Sca-1+CD31− and Lin−CD45−Sca-1+CD31+ surface antigens using flow-activated cell sorting; (2 investigate their differentiation potential; and (3 determine the molecular basis for differences in stemness characteristics between cell subtypes. The results indicated that mouse heart-derived Sca-1+CD31− cells were multipotent and retained the ability to differentiate into different cardiac cell lineages, but Sca-1+CD31+ cells did not. Integrated analysis of microRNA and mRNA expression indicated that 20 microRNAs and 49 mRNAs were inversely associated with Sca-1+CD31− and Sca-1+CD31+ subtype stemness characteristics. In particular, mmu-miR-322-5p had more targeted and inversely associated genes and transcription factors and might have higher potential for CSC/CPCs differentiation.

  14. Dynamic mutation analysis of a SCA3 Chinese Han family and prenatal diagnosis

    Directory of Open Access Journals (Sweden)

    LI Jing

    2012-06-01

    Full Text Available Objective To explore the clinical features, genetic characters and the importance of prenatal diagnosis in spinocerebellar ataxia 3 (SCA3 patients. Methods SCA3/ATXN3 gene was determined by using PCR and segmental analysis techniques in 2 patients among a SCA3 Chinese Han family which included 9 patients in four generations. One patient was the proband's fetus. The clinical characters were also documented and analyzed in this family. Results There were 9 patients in this family with autosomal dominant inheritance feature. The initial symptoms in all affected members except the fetus were the gait disorders accompanied by dysphasia. Inability of upward gaze and bilateral Barbinski's signs were noted in proband. The onset age became earlier from generation to generation in this family which was around 50 year-old, 40 to 45 year-old, 28 year-old in generation Ⅰ, Ⅱ and Ⅲ, respectively. CAG repeats in SCA3/ATXN3 allele were 77 in proband, as well as in the fetus, while the normal SCA3/ATXN3 allele CAG repeats were less than 44. Conclusion SCA3 is the most frequent subtype of SCA in Asian. Unsteadiness of gait are first noted in most patients accompanied by other different symptoms and signs. Genetic anticipation was found in SCA3. But gene analysis revealed less dynamic mutation frequence in this family. Since there was no effective treatment in SCA3, hereditary consultation and prenatal diagnosis play an important role in disease prevention and hereditary.

  15. Impacts of the SCA Core Framework on High Speed Broadband Waveform in SDR Handheld System

    Science.gov (United States)

    Oh, Sangchul; Park, Namhoon; Kwon, Ohjun; Kim, Yeongjin

    In this paper, we have shown a major element occupying the large portion of software communications architecture (SCA)-based software defined radio (SDR) handheld embedded system and an important feature for implementing a high speed broadband radio to an SCA waveform through a couple of experiments. First, this paper identifies the main items possessing the large portion of SCA-based SDR handheld embedded system by the experiment on the target platform which is similar to a commercial mobile handheld system. Both the world interoperabillity for microwave access (WiMAX) and high speed downlink packet access (HSDPA) waveform software packages are used as an SCA waveform application. This paper also presents the results of the relative binary size distribution of SCA software resources for looking for the major elements making an SCA-based SDR handheld embedded system heavier. As a result, when focusing on the relative weight portion of SCA core framework (CF), the SCA CF takes 16% up and others have 84% out of the whole binary size distribution of SCA software resources. The results of the experiment give us notice that the weight portion of SCA CF is minor and compatible with the overall software binary size needs of an SCA-based SDR handheld embedded system, on the other hand, the practical problem on the lightweight is in a common object request broker architecture (CORBA) and extensible markup language (XML) parser resources. Second, this paper describes an important feature for implementing a high speed broadband radio to an SCA waveform and presents the performance evaluation results of the SCA port communication on both power PC (PPC) 405 and x86 processor platforms. The PPC 405 platform, which is similar to a commercial mobile handset, takes the value of average round trip time (RTT) with a maximum of thirty six millisecond. The x86 platform, however, which is analogous to a server platform, maintains stable micro-second resolution. From our experiments, we

  16. Rainfall Estimation over the Nile Basin using an Adapted Version of the SCaMPR Algorithm

    Science.gov (United States)

    Habib, E. H.; Kuligowski, R. J.; Elshamy, M. E.; Ali, M. A.; Haile, A.; Amin, D.; Eldin, A.

    2011-12-01

    Management of Egypt's Aswan High Dam is critical not only for flood control on the Nile but also for ensuring adequate water supplies for most of Egypt since rainfall is scarce over the vast majority of its land area. However, reservoir inflow is driven by rainfall over Sudan, Ethiopia, Uganda, and several other countries from which routine rain gauge data are sparse. Satellite-derived estimates of rainfall offer a much more detailed and timely set of data to form a basis for decisions on the operation of the dam. A single-channel infrared algorithm is currently in operational use at the Egyptian Nile Forecast Center (NFC). This study reports on the adaptation of a multi-spectral, multi-instrument satellite rainfall estimation algorithm (Self-Calibrating Multivariate Precipitation Retrieval, SCaMPR) for operational application over the Nile Basin. The algorithm uses a set of rainfall predictors from multi-spectral Infrared cloud top observations and self-calibrates them to a set of predictands from Microwave (MW) rain rate estimates. For application over the Nile Basin, the SCaMPR algorithm uses multiple satellite IR channels recently available to NFC from the Spinning Enhanced Visible and Infrared Imager (SEVIRI). Microwave rain rates are acquired from multiple sources such as SSM/I, SSMIS, AMSU, AMSR-E, and TMI. The algorithm has two main steps: rain/no-rain separation using discriminant analysis, and rain rate estimation using stepwise linear regression. We test two modes of algorithm calibration: real-time calibration with continuous updates of coefficients with newly coming MW rain rates, and calibration using static coefficients that are derived from IR-MW data from past observations. We also compare the SCaMPR algorithm to other global-scale satellite rainfall algorithms (e.g., 'Tropical Rainfall Measuring Mission (TRMM) and other sources' (TRMM-3B42) product, and the National Oceanographic and Atmospheric Administration Climate Prediction Center (NOAA

  17. Ataxin-1 regulates the cerebellar bioenergetics proteome through the GSK3β-mTOR pathway which is altered in Spinocerebellar ataxia type 1 (SCA1).

    Science.gov (United States)

    Sánchez, Ivelisse; Balagué, Eudald; Matilla-Dueñas, Antoni

    2016-09-15

    A polyglutamine expansion within the ataxin-1 protein (ATXN1) underlies spinocerebellar ataxia type-1 (SCA1), a neurological disorder mainly characterized by ataxia and cerebellar deficits. In SCA1, both loss and gain of ATXN1 biological functions contribute to cerebellar pathogenesis. However, the critical ATXN1 functions and pathways involved remain unclear. To further investigate the early signalling pathways regulated by ATXN1, we performed an unbiased proteomic study of the Atxn1-KO 5-week-old mice cerebellum. Here, we show that lack of ATXN1 expression induces early alterations in proteins involved in glycolysis [pyruvate kinase, muscle, isoform 1 protein (PKM-i1), citrate synthase (CS), glycerol-3-phosphate dehydrogenase 2 (GPD2), glucose-6-phosphate isomerase (GPI), alpha -: enolase (ENO1)], ATP synthesis [CS, Succinate dehydrogenase complex,subunit A (SDHA), ATP synthase subunit d, mitochondrial (ATP5H)] and oxidative stress [peroxiredoxin-6 (PRDX6), aldehyde dehydrogenase family 1, subfamily A1, 10-formyltetrahydrofolate dehydrogenase]. In the SCA1 mice, several of these proteins (PKM-i1, ATP5H, PRDX6, proteome subunit A6) were down-regulated and ATP levels decreased. The underlying mechanism does not involve modulation of mitochondrial biogenesis, but dysregulation of the activity of the metabolic regulators glycogen synthase kinase 3B (GSK3β), decreased in Atxn1-KO and increased in SCA1 mice, and mechanistic target of rapamycin (serine/threonine kinase) (mTOR), unchanged in the Atxn1-KO and decreased in SCA1 mice cerebellum before the onset of ataxic symptoms. Pharmacological inhibition of GSK3β and activation of mTOR in a SCA1 cell model ameliorated identified ATXN1-regulated metabolic proteome and ATP alterations. Taken together, these results point to an early role of ATXN1 in the regulation of bioenergetics homeostasis in the mouse cerebellum. Moreover, data suggest GSK3β and mTOR pathways modulate this ATXN1 function in SCA1 pathogenesis that

  18. Immunomagnetic Separation of Fat Depot-specific Sca1high Adipose-derived Stem Cells (ASCs).

    Science.gov (United States)

    Barnes, Richard H; Chun, Tae-Hwa

    2016-08-11

    The isolation of adipose-derived stem cells (ASCs) is an important method in the field of adipose tissue biology, adipogenesis, and extracellular matrix (ECM) remodeling. In vivo, ECM-rich environment consisting of fibrillar collagens provides a structural support to adipose tissues during the progression and regression of obesity. Physiological ECM remodeling mediated by matrix metalloproteinases (MMPs) plays a major role in regulating adipose tissue size and function(1,2). The loss of physiological collagenolytic ECM remodeling may lead to excessive collagen accumulation (tissue fibrosis), macrophage infiltration, and ultimately, a loss of metabolic homeostasis including insulin resistance(3,4). When a phenotypic change of the adipose tissue is observed in gene-targeted mouse models, isolating primary ASCs from fat depots for in vitro studies is an effective approach to define the role of the specific gene in regulating the function of ASCs. In the following, we define an immunomagnetic separation of Sca1(high) ASCs.

  19. The role of interruptions in polyQ in the pathology of SCA1.

    Directory of Open Access Journals (Sweden)

    Rajesh P Menon

    Full Text Available At least nine dominant neurodegenerative diseases are caused by expansion of CAG repeats in coding regions of specific genes that result in abnormal elongation of polyglutamine (polyQ tracts in the corresponding gene products. When above a threshold that is specific for each disease the expanded polyQ repeats promote protein aggregation, misfolding and neuronal cell death. The length of the polyQ tract inversely correlates with the age at disease onset. It has been observed that interruption of the CAG tract by silent (CAA or missense (CAT mutations may strongly modulate the effect of the expansion and delay the onset age. We have carried out an extensive study in which we have complemented DNA sequence determination with cellular and biophysical models. By sequencing cloned normal and expanded SCA1 alleles taken from our cohort of ataxia patients we have determined sequence variations not detected by allele sizing and observed for the first time that repeat instability can occur even in the presence of CAG interruptions. We show that histidine interrupted pathogenic alleles occur with relatively high frequency (11% and that the age at onset inversely correlates linearly with the longer uninterrupted CAG stretch. This could be reproduced in a cellular model to support the hypothesis of a linear behaviour of polyQ. We clarified by in vitro studies the mechanism by which polyQ interruption slows down aggregation. Our study contributes to the understanding of the role of polyQ interruption in the SCA1 phenotype with regards to age at disease onset, prognosis and transmission.

  20. Investigating function and connectivity of morphometric findings — Exemplified on cerebellar atrophy in spinocerebellar ataxia 17 (SCA17)

    Science.gov (United States)

    Reetz, Kathrin; Dogan, Imis; Rolfs, Arndt; Binkofski, Ferdinand; Schulz, Jörg B.; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

    2016-01-01

    Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia but also a broad spectrum of other neuropsychiatric signs. As anatomical and structural studies have shown severe cerebellar atrophy in SCA17 and a differentiation of the human cerebellum into an anterior sensorimotor and posterior cognitive/emotional partition has been implicated, we aimed at investigating functional connectivity patterns of two cerebellar clusters of atrophy revealed by a morphometric analysis in SCA17 patients. In particular, voxel-based morphometry (VBM) revealed a large cluster of atrophy in SCA17 in the bilateral anterior cerebellum (lobule V) and another one in the left posterior cerebellum (lobules IX, VIIb, VIIIA, VIIIB). These two cerebellar clusters were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modeling (MACM) and task-free resting state connectivity analysis. Results demonstrated first consistent functional connectivity throughout the cerebellum itself; the anterior cerebellar seed showed stronger connectivity to lobules V, VI and to some extent I–IV, and the posterior cerebellar seed to the posterior lobules VI–IX. Importantly, the cerebellar anterior seed also showed consistently stronger functional connectivity than the posterior one with pre- and motor areas as well as the primary somatosensory cortex. In turn, task-based task-independent functional connectivity analyses revealed that the cerebellar posterior seed was linked with fronto-temporo-parietal areas as well as partly the insula and the thalamus, i.e., brain regions implicated in cognitive and affective processes. Functional characterization of experiments activating either cerebellar seed further corroborated this notion, revealing mainly motor-related functions for the anterior cluster and predominantly cognitive functions were associated for the posterior one. The

  1. Investigating function and connectivity of morphometric findings--exemplified on cerebellar atrophy in spinocerebellar ataxia 17 (SCA17).

    Science.gov (United States)

    Reetz, Kathrin; Dogan, Imis; Rolfs, Arndt; Binkofski, Ferdinand; Schulz, Jörg B; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

    2012-09-01

    Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia but also a broad spectrum of other neuropsychiatric signs. As anatomical and structural studies have shown severe cerebellar atrophy in SCA17 and a differentiation of the human cerebellum into an anterior sensorimotor and posterior cognitive/emotional partition has been implicated, we aimed at investigating functional connectivity patterns of two cerebellar clusters of atrophy revealed by a morphometric analysis in SCA17 patients. In particular, voxel-based morphometry (VBM) revealed a large cluster of atrophy in SCA17 in the bilateral anterior cerebellum (lobule V) and another one in the left posterior cerebellum (lobules IX, VIIb, VIIIA, VIIIB). These two cerebellar clusters were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modeling (MACM) and task-free resting state connectivity analysis. Results demonstrated first consistent functional connectivity throughout the cerebellum itself; the anterior cerebellar seed showed stronger connectivity to lobules V, VI and to some extent I-IV, and the posterior cerebellar seed to the posterior lobules VI-IX. Importantly, the cerebellar anterior seed also showed consistently stronger functional connectivity than the posterior one with pre- and motor areas as well as the primary somatosensory cortex. In turn, task-based task-independent functional connectivity analyses revealed that the cerebellar posterior seed was linked with fronto-temporo-parietal areas as well as partly the insula and the thalamus, i.e., brain regions implicated in cognitive and affective processes. Functional characterization of experiments activating either cerebellar seed further corroborated this notion, revealing mainly motor-related functions for the anterior cluster and predominantly cognitive functions were associated for the posterior one. The differential

  2. Validation of a Bayesian reconstruction approach to estimate snow water equivalent via assimilation of MODIS fractional SCA data

    Science.gov (United States)

    Girotto, M.; Margulis, S. A.; Durand, M. T.; Molotch, N. P.

    2010-12-01

    Seasonal snowmelt runoff represents one of the major components of water resources in many regions of the world. Lack of knowledge of its spatial and temporal characteristics limits our ability to monitor and predict this vital source of water. Process understanding stands to benefit from an accurate spatial and temporal characterization of the mountain snow water equivalent (SWE) spatial distribution and evolution. A probabilistic approach that takes into account sources of uncertainty from all input data streams (including remote sensing and models and their inputs) while estimating SWE is desired. This work applied a Bayesian reanalysis data assimilation system, similar to an Ensemble Kalman Smoother, capable of merging remotely sensed Snow Covered Area (SCA) data into prediction models, and at the same time account for the limitations of each. Preliminary analysis has identified and characterized the key factors responsible for SWE estimation accuracy, and developed models able to represent their uncertainties within the probabilistic data assimilation approach. The approach was implemented for the characterization of spatially and temporally continuous SWE over a test domain in the Sequoia National Park region of the Sierra Nevada. To assess the performance of the method, SWE spatial estimates are compared with estimates from intense field campaigns, and existing snow-pillow records. SCA estimates from both the standard fractional MODIS product and the advanced MODSCAG are investigated as they have been derived with different retrieval algorithms. The system is designed to use readily available forcing information from the North American Land Data Assimilation System (NLDAS). Prior estimates of SWE are obtained by forcing a land surface model with prior probability distributions of snowfall obtained from the NLDAS precipitation product. A reanalysis step conditions the prior estimates on SCA measurements. A series of preliminary analyses focus on identifying

  3. SCaMF–RM: A Fused High-Resolution Land Cover Product of the Rocky Mountains

    Directory of Open Access Journals (Sweden)

    Nicolás Rodríguez-Jeangros

    2017-09-01

    Full Text Available Land cover (LC products, derived primarily from satellite spectral imagery, are essential inputs for environmental studies because LC is a critical driver of processes involved in hydrology, ecology, and climatology, among others. However, existing LC products each have different temporal and spatial resolutions and different LC classes that rarely provide the detail required by these studies. Using multiple existing LC products, we implement our Spatiotemporal Categorical Map Fusion (SCaMF methodology over a large region of the Rocky Mountains (RM, encompassing sections of six states, to create a new LC product, SCaMF–RM. To do this, we must adapt SCaMF to address the prediction of LC in large space–time regions that present nonstationarities, and we add more flexibility in the LC classifications of the predicted product. SCaMF–RM is produced at two high spatial resolutions, 30 and 50 m, and a yearly frequency for the 30-year period 1983–2012. When multiple products are available in time, we illustrate how SCaMF–RM captures relevant information from the different LC products and improves upon flaws observed in other products. Future work needed includes an exhaustive validation not only of SCaMF–RM but also of all input LC products.

  4. SCaMF–RM: A Fused High-Resolution Land Cover Product of the Rocky Mountains

    KAUST Repository

    Rodríguez-Jeangros, Nicolás

    2017-10-02

    Land cover (LC) products, derived primarily from satellite spectral imagery, are essential inputs for environmental studies because LC is a critical driver of processes involved in hydrology, ecology, and climatology, among others. However, existing LC products each have different temporal and spatial resolutions and different LC classes that rarely provide the detail required by these studies. Using multiple existing LC products, we implement our Spatiotemporal Categorical Map Fusion (SCaMF) methodology over a large region of the Rocky Mountains (RM), encompassing sections of six states, to create a new LC product, SCaMF–RM. To do this, we must adapt SCaMF to address the prediction of LC in large space–time regions that present nonstationarities, and we add more flexibility in the LC classifications of the predicted product. SCaMF–RM is produced at two high spatial resolutions, 30 and 50 m, and a yearly frequency for the 30-year period 1983–2012. When multiple products are available in time, we illustrate how SCaMF–RM captures relevant information from the different LC products and improves upon flaws observed in other products. Future work needed includes an exhaustive validation not only of SCaMF–RM but also of all input LC products.

  5. Crystallographic and Computational Analyses of AUUCU Repeating RNA That Causes Spinocerebellar Ataxia Type 10 (SCA10).

    Science.gov (United States)

    Park, HaJeung; González, Àlex L; Yildirim, Ilyas; Tran, Tuan; Lohman, Jeremy R; Fang, Pengfei; Guo, Min; Disney, Matthew D

    2015-06-23

    Spinocerebellar ataxia type 10 (SCA10) is caused by a pentanucleotide repeat expansion of r(AUUCU) within intron 9 of the ATXN10 pre-mRNA. The RNA causes disease by a gain-of-function mechanism in which it inactivates proteins involved in RNA biogenesis. Spectroscopic studies showed that r(AUUCU) repeats form a hairpin structure; however, there were no high-resolution structural models prior to this work. Herein, we report the first crystal structure of model r(AUUCU) repeats refined to 2.8 Å and analysis of the structure via molecular dynamics simulations. The r(AUUCU) tracts adopt an overall A-form geometry in which 3 × 3 nucleotide (5')UCU(3')/(3')UCU(5') internal loops are closed by AU pairs. Helical parameters of the refined structure as well as the corresponding electron density map on the crystallographic model reflect dynamic features of the internal loop. The computational analyses captured dynamic motion of the loop closing pairs, which can form single-stranded conformations with relatively low energies. Overall, the results presented here suggest the possibility for r(AUUCU) repeats to form metastable A-from structures, which can rearrange into single-stranded conformations and attract proteins such as heterogeneous nuclear ribonucleoprotein K (hnRNP K). The information presented here may aid in the rational design of therapeutics targeting this RNA.

  6. Single cell analysis reveals gametic and tissue-specific instability of the SCA1 CAG repeat

    Energy Technology Data Exchange (ETDEWEB)

    Chong, S.S.; McCall, A.E.; Cota, J. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Spinocerebellar ataxia type 1 is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat within the SCA1 gene on chromosome 6p22-23. We performed a comparative analysis of the SCA1 CAG repeat from blood and sperm of an affected male. Genomic amplification revealed a broader smear of the SCA1 allele product from sperm compared to that from peripheral blood leukocytes (PBL). To resolve this observed difference, we analyzed single sperm directly and demonstrate that the SCA1 allele in PBL is also heterogeneous, although the range of variability in allele sizes is much less than that observed in sperm. Limited genome analysis was also performed on PBL DNA from an unaffected individual with an upper normal allele of 36 repeats in parallel with an affected individual with an expanded allele of 40 repeats. The 36 repeat normal allele, which contains a CAT interruption, was completely stable compared to the uninterrupted repeat of the SCA1 allele, demonstrating a direct correlation between absence of a CAT interruption and somatic instability of the repeat. We also analyzed the size of the CAG repeat in tissues derived from various brain regions from a patient with juvenile-onset disease to determine if the size of the expansion correlated with the site of neuropathology. The results clearly show tissue-specific differences in mosaicism of repeat length. More importantly, the pattern of tissue-specific differences in repeat-length mosaicism in SCA1 within the brain parallels those seen in Huntington disease. In both disorders the expanded alleles are smaller in cerebellar tissue. These results suggest that the observed tissue-specific differences in instability of the SCA1 CAG repeat, either within the brain or between blood and sperm, are a function of the intracellular milieu or the intrinsic replicative potential of the various celltypes.

  7. Sca1-positive murine pituitary adenoma cells show tumor growth advantage

    Science.gov (United States)

    Donangelo, Ines; Ren, Song-Guang; Eigler, Tamar; Svendsen, Clive; Melmed, Shlomo

    2014-01-01

    The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. We investigated whether cells within pituitary adenomas that spontaneously develop in Rb+/− mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with EGF and bFGF. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1+ cell population that showed increased sphere formation potential, lower hormone mRNA expression, higher expression of stem cell markers (Notch1, Sox2, Nestin), and increased proliferation rates. When transplanted into NOD scid gamma mice brains, Sca1+ pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 [100%] vs. 7/12 [54%] of mice transplanted with Sca1+ and Sca1− cells, respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that those derived from Sca1+ pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1+ cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells. PMID:24481638

  8. The Role of Clear Sky Identification in the Study of Cloud Radiative Effects: Combine Analysis from ISCCP and the Scanner of Radiation Budget (ScaRaB)

    Science.gov (United States)

    Rossow, W. B.; Stubenrauch, C. J.; Briand, V.; Hansen, James E. (Technical Monitor)

    2001-01-01

    obtained from the ScaRaB adapted ISCCP clear sky identifications. The latter are close to (about 1 W/sq m higher) fluxes corresponding to clear sky regions from original ISCCP data, whereas ScaRaB clear sky LW fluxes obtained with the original ISCCP identification lie about 1 to 2 W/sq m below. Especially in the tropics where water vapor abundance is high, the ERBE clear sky LW fluxes seem to be systematically overestimated by about 4 W/sq m, and SW fluxes are lower by about 5 to 10 W/sq m. However, the uncertainty in the analysis of monthly mean zonal cloud radiative effects is also produced by the low frequency of clear sky occurrence, illustrated when averaging over pixels or even over regions of 4deg longitude x 5deg latitude, corresponding to the spatial resolution of General Circulation Models. The systematic bias in the clear sky fluxes is not reflected in the zonal cloud radiative effects, because the clear sky regions selected by the different algorithms can occur in different geographic regions with different cloud properties.

  9. CitySCaPE: Moving beyond indifference in education for pre-registration nurses about learning disability.

    Science.gov (United States)

    Saunder, Lorna; Knight, Rachael-Anne

    2017-09-01

    People with learning disabilities and Autism continue to suffer from the delivery of ineffective and inadequate care from health services CitySCaPE (City Simulated Community and Practice Environment) is a multi media resource delivering a simulation of situations student nurses may encounter in relation to service users with learning disabilities. The resource is applicable to adult, mental health and children's nursing. It is delivered in a blended approach to students in the first part of their programme as part of their simulated practice. Following the implementation of the resource an evaluation of student experience was undertaken using a mixed methods approach. 146 responses were obtained to a questionnaire containing quantitative and qualitative data. The findings indicate that this is a pedagogy that suits a variety of learning styles, is deemed to be realistic and improves the understanding of nursing students about the care of people with learning disabilities in generic practice areas. It is anticipated that CitySCaPE can be used as a model for delivery of practice based learning in areas that are often challenging to teach and demonstrate using a service user and person centred approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Stance instability in preclinical SCA1 mutation carriers: A 4-year prospective posturography study.

    Science.gov (United States)

    Nanetti, Lorenzo; Alpini, Dario; Mattei, Valentina; Castaldo, Anna; Mongelli, Alessia; Brenna, Greta; Gellera, Cinzia; Mariotti, Caterina

    2017-09-01

    We aimed to study postural balance in preclinical Spinocerebellar ataxia type 1 (SCA1) mutation carriers to identify and observe specific motor functional deficit before evident clinical manifestation. Participants were 9 asymptomatic SCA1 mutation carriers (6M/3F), aged 31.8±7years (range 22-44), and 17 age-matched non-carrier controls (5M/12F) (age 18-42). Subjects underwent postural tests on a force platform (Tetrax®-IBS, Sunlight Medical Ltd.) with and without visual feedback. Amount of body sway was represented by stability index (ST). Tests were repeated after 2- and 4-years. Estimated years to onset were calculated. In controls, ST was unchanged from baseline to 4-year evaluations in all standing conditions. SCA1 mutation carriers performed similarly to controls in the postural tasks with open eyes, whereas in conditions without visual feedback SCA1 carriers had significantly higher ST than controls at all longitudinal evaluations. Close-to-disease onset carriers (≤7years) showed more prominent time-dependent stance abnormalities (p<0.0001 for all comparisons). Traceable and progressive postural abnormalities can be observed in preclinical close-to-onset SCA1 carriers. Quantitative analysis of stance could represent a promising outcome measure in clinical trials including preclinical subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. SCA2 is not a major locus for ADCA type I in French families

    Energy Technology Data Exchange (ETDEWEB)

    Cancel, G.; Stevanin, G.; Duerr, A.; Penet, C. [INSERM, Paris (France)] [and others

    1995-10-09

    Autosomal dominant cerebellar ataxias (ADCA) of type I, a group of clinically heterogeneous neurodegenerative disorders, are known to be genetically heterogeneous since a second locus for ADCA type I (SCA2) has been identified on the long arm of chromosome 12. Linkage analysis was performed in 7 French ADCA type I families in order to estimate its frequency. We analysed 121 individuals, 39 of whom were affected. In 6 families, the SCA2 candidate interval, spanning 12.8 cM, was excluded by bi- and multipoint analysis. In one family (SAL-315), however, the maximal positive lod score reached 2.03 at the D12S79 locus. A posterior probability of 94% in favor of linkage to SCA2 was calculated by homogeneity analysis. The clinical profile of this family was similar to that of previously described SCA1 and non-SCA1 families, except that dementia was observed in 2 out of 6 patients. This may be a clinical idiosyncrasy in this family and was insufficient for a genotype-phenotype correlation. 14 refs., 1 fig., 1 tab.

  12. Pengaruh Sales Call Anxiety (SCA) Pada Kinerja Salespersons Asuransi Jiwa Dengan Trait Negative Affectivity (Trait-Na)

    OpenAIRE

    Rita, Rita

    2012-01-01

    This study empirically examines the effect of sales call anxiety (SCA) on salesperson performance, good performance in the form of sales volume and sales interactions. This study tested the hypothesis to identify early factors (antecedents) that may affect the sales call anxiety (SCA). Initial factors suspected as the cause of anxiety in sales interactions (SCA) are divided into two conditions, namely canvassing and closing condition. Canvassing consisted of meeting new people, customer with ...

  13. Pengaruh Sales Call Anxiety (SCA) pada Kinerja Salespersons Asuransi Jiwa dengan Trait Negative Affectivity (Trait-Na)

    OpenAIRE

    Rita Rita

    2012-01-01

    This study empirically examines the effect of sales call anxiety (SCA) on salesperson performance, good performance in the form of sales volume and sales interactions. This study tested the hypothesis to identify early factors (antecedents) that may affect the sales call anxiety (SCA). Initial factors suspected as the cause of anxiety in sales interactions (SCA) are divided into two conditions, namely canvassing and closing condition. Canvassing consisted of meeting new people, customer with ...

  14. Discovering gene expression patterns in time course microarray experiments by ANOVA-SCA.

    Science.gov (United States)

    Nueda, María José; Conesa, Ana; Westerhuis, Johan A; Hoefsloot, Huub C J; Smilde, Age K; Talón, Manuel; Ferrer, Alberto

    2007-07-15

    Designed microarray experiments are used to investigate the effects that controlled experimental factors have on gene expression and learn about the transcriptional responses associated with external variables. In these datasets, signals of interest coexist with varying sources of unwanted noise in a framework of (co)relation among the measured variables and with the different levels of the studied factors. Discovering experimentally relevant transcriptional changes require methodologies that take all these elements into account. In this work, we develop the application of the Analysis of variance-simultaneous component analysis (ANOVA-SCA) Smilde et al. Bioinformatics, (2005) to the analysis of multiple series time course microarray data as an example of multifactorial gene expression profiling experiments. We denoted this implementation as ASCA-genes. We show how the combination of ANOVA-modeling and a dimension reduction technique is effective in extracting targeted signals from data by-passing structural noise. The methodology is valuable for identifying main and secondary responses associated with the experimental factors and spotting relevant experimental conditions. We additionally propose a novel approach for gene selection in the context of the relation of individual transcriptional patterns to global gene expression signals. We demonstrate the methodology on both real and synthetic datasets. ASCA-genes has been implemented in the statistical language R and is available at http://www.ivia.es/centrodegenomica/bioinformatics.htm. Supplementary data are available at Bioinformatics online.

  15. Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence.

    Science.gov (United States)

    Velázquez-Pérez, Luis; Tünnerhoff, Johannes; Rodríguez-Labrada, Roberto; Torres-Vega, Reidenis; Ruiz-Gonzalez, Yusely; Belardinelli, Paolo; Medrano-Montero, Jacqueline; Canales-Ochoa, Nalia; González-Zaldivar, Yanetza; Vazquez-Mojena, Yaimeé; Auburger, Georg; Ziemann, Ulf

    2017-12-01

    Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity. CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles. Significant reductions of EEG-EMG and EMG-EMG coherences were observed in the SCA2 patients, and to a similar extent in the prodromal SCA2 mutation carriers. In prodromal SCA2, EEG-EMG and EMG-EMG coherences correlated with the predicted time to ataxia onset. Findings indicate early CST neurodegeneration in SCA2. EEG-EMG and EMG-EMG coherence may serve as biomarkers of early CST neurodegeneration in prodromal SCA2 mutation carriers. Findings are important for developing preclinical disease markers in the context of currently emerging disease-modifying therapies of neurodegenerative disorders. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. SBIR Technology Applications to Space Communications and Navigation (SCaN)

    Science.gov (United States)

    Liebrecht, Phil; Eblen, Pat; Rush, John; Tzinis, Irene

    2010-01-01

    This slide presentation reviews the mission of the Space Communications and Navigation (SCaN) Office with particular emphasis on opportunities for technology development with SBIR companies. The SCaN office manages NASA's space communications and navigation networks: the Near Earth Network (NEN), the Space Network (SN), and the Deep Space Network (DSN). The SCaN networks nodes are shown on a world wide map and the networks are described. Two types of technologies are described: Pull technology, and Push technologies. A listing of technology themes is presented, with a discussion on Software defined Radios, Optical Communications Technology, and Lunar Lasercom Space Terminal (LLST). Other technologies that are being investigated are some Game Changing Technologies (GCT) i.e., technologies that offer the potential for improving comm. or nav. performance to the point that radical new mission objectives are possible, such as Superconducting Quantum Interference Filters, Silicon Nanowire Optical Detectors, and Auto-Configuring Cognitive Communications

  17. Neural substrates of motor and cognitive dysfunctions in SCA2 patients: A network based statistics analysis

    Directory of Open Access Journals (Sweden)

    G. Olivito

    2017-01-01

    In the present study, the network-based statistics (NBS approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes.

  18. SCaN Network Ground Station Receiver Performance for Future Service Support

    Science.gov (United States)

    Estabrook, Polly; Lee, Dennis; Cheng, Michael; Lau, Chi-Wung

    2012-01-01

    Objectives: Examine the impact of providing the newly standardized CCSDS Low Density Parity Check (LDPC) codes to the SCaN return data service on the SCaN SN and DSN ground stations receivers: SN Current Receiver: Integrated Receiver (IR). DSN Current Receiver: Downlink Telemetry and Tracking (DTT) Receiver. Early Commercial-Off-The-Shelf (COTS) prototype of the SN User Service Subsystem Component Replacement (USS CR) Narrow Band Receiver. Motivate discussion of general issues of ground station hardware design to enable simple and cheap modifications for support of future services.

  19. Expansion of the Spinocerebellar ataxia type 10 (SCA10 repeat in a patient with Sioux Native American ancestry.

    Directory of Open Access Journals (Sweden)

    Khalaf Bushara

    Full Text Available Spinocerebellar ataxia type 10 (SCA10, an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described "SCA10 haplotype". This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas.

  20. SMRT Sequencing of Long Tandem Nucleotide Repeats in SCA10 Reveals Unique Insight of Repeat Expansion Structure.

    Science.gov (United States)

    McFarland, Karen N; Liu, Jilin; Landrian, Ivette; Godiska, Ronald; Shanker, Savita; Yu, Fahong; Farmerie, William G; Ashizawa, Tetsuo

    2015-01-01

    A large, non-coding ATTCT repeat expansion causes the neurodegenerative disorder, spinocerebellar ataxia type 10 (SCA10). In a subset of SCA10 patients, interruption motifs are present at the 5' end of the expansion and strongly correlate with epileptic seizures. Thus, interruption motifs are a predictor of the epileptic phenotype and are hypothesized to act as a phenotypic modifier in SCA10. Yet, the exact internal sequence structure of SCA10 expansions remains unknown due to limitations in current technologies for sequencing across long extended tracts of tandem nucleotide repeats. We used the third generation sequencing technology, Single Molecule Real Time (SMRT) sequencing, to obtain full-length contiguous expansion sequences, ranging from 2.5 to 4.4 kb in length, from three SCA10 patients with different clinical presentations. We obtained sequence spanning the entire length of the expansion and identified the structure of known and novel interruption motifs within the SCA10 expansion. The exact interruption patterns in expanded SCA10 alleles will allow us to further investigate the potential contributions of these interrupting sequences to the pathogenic modification leading to the epilepsy phenotype in SCA10. Our results also demonstrate that SMRT sequencing is useful for deciphering long tandem repeats that pose as "gaps" in the human genome sequence.

  1. SMRT Sequencing of Long Tandem Nucleotide Repeats in SCA10 Reveals Unique Insight of Repeat Expansion Structure.

    Directory of Open Access Journals (Sweden)

    Karen N McFarland

    Full Text Available A large, non-coding ATTCT repeat expansion causes the neurodegenerative disorder, spinocerebellar ataxia type 10 (SCA10. In a subset of SCA10 patients, interruption motifs are present at the 5' end of the expansion and strongly correlate with epileptic seizures. Thus, interruption motifs are a predictor of the epileptic phenotype and are hypothesized to act as a phenotypic modifier in SCA10. Yet, the exact internal sequence structure of SCA10 expansions remains unknown due to limitations in current technologies for sequencing across long extended tracts of tandem nucleotide repeats. We used the third generation sequencing technology, Single Molecule Real Time (SMRT sequencing, to obtain full-length contiguous expansion sequences, ranging from 2.5 to 4.4 kb in length, from three SCA10 patients with different clinical presentations. We obtained sequence spanning the entire length of the expansion and identified the structure of known and novel interruption motifs within the SCA10 expansion. The exact interruption patterns in expanded SCA10 alleles will allow us to further investigate the potential contributions of these interrupting sequences to the pathogenic modification leading to the epilepsy phenotype in SCA10. Our results also demonstrate that SMRT sequencing is useful for deciphering long tandem repeats that pose as "gaps" in the human genome sequence.

  2. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.A11

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Borland, Helena; Hasholt, Lis Frydenreich

    2016-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by a CAG-repeat expanding mutation in ATXN3. We generated induced pluripotent stem cells (iPSCs) from a SCA3 patient by electroporation of dermal fibroblasts with episomal plasmids encoding L-MYC, LIN28...

  3. Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line SCA3.B11

    DEFF Research Database (Denmark)

    Hansen, Susanne Kofoed; Borland, Helena; Hasholt, Lis Frydenreich

    2016-01-01

    Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disease caused by an expansion of the CAG-repeat in ATXN3. In this study, induced pluripotent stem cells (iPSCs) were generated from SCA3 patient dermal fibroblasts by electroporation with episomal plasmids encoding L...

  4. The Ly-6A (Sca-1) GFP transgene is expressed in all adult mouse hematopoietic stem cells

    NARCIS (Netherlands)

    X. Ma (Xiaoqian); C.I. Robin; K. Ottersbach (Katrin); E.A. Dzierzak (Elaine)

    2002-01-01

    textabstractThe Sca-1 cell surface glycoprotein is used routinely as a marker of adult hematopoietic stem cells (HSCs), allowing a >100-fold enrichment of these rare cells from the bone marrow of the adult mouse. The Sca-1 protein is encoded by the Ly-6A/E gene, a small 4-exon gene

  5. Investigating B Cell Development, Natural and Primary Antibody Responses in Ly-6A/Sca-1 Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Morgan A Jones

    Full Text Available Ly-6A/Stem cell antigen-1 (Ly-6A/Sca-1 is a glycosylphosphatidylinositol-anchored protein expressed on many cell types including hematopoietic stem cells (HSCs and early lymphoid-specific progenitors. Ly-6A/Sca-1 is expressed on CD4+ T cells and plays a role in regulating cellular responses to foreign antigens. The role of Ly-6A/Sca-1 in primary antibody responses has not been defined. To investigate whether Ly-6A/Sca-1 functions in humoral immunity, we first injected Ly-6A/Sca-1-deficient and wild-type control mice with chicken ovalbumin (c-Ova protein mixed with an adjuvant. We then assessed the ability of the mice to generate a primary antibody response against cOva. We further examined the development of B cells and circulating antibody isotypes in non-immunized Ly-6A/Sca-1deficient mice to determine if Ly6A/Sca-1 functions in development irrespective of antigen-specific immune activation. Ly-6A/Sca-1/Sca-1-deficient mice did not show any significant changes in the number of B lymphocytes in the bone marrow and peripheral lymphoid tissues. Interestingly, Ly-6A/Sca-1/Sca-1-/- mice have significantly elevated serum levels of IgA with λ light chains compared to wild type controls. B cell clusters with high reactivity to anti-IgA λ monoclonal antibody were detected in the lamina propria of the gut, though this was not observed in the bone marrow and peripheral lymphoid tissues. Despite these differences, the Ly-6A/Sca-1deficient mice generated a similar primary antibody response when compared to the wild-type mice. In summary, we conclude that the primary antibody response to cOva antigen is similar in Ly-6A/Sca-1deficient and sufficient mice. In addition, we report significantly higher expression of the immunoglobulin λ light chain by B cells in lamina propria of Ly-6A/Sca-1deficient mice when compared to the wild-type control.

  6. Types d'êtres discursifs dans la ScaPoLine

    DEFF Research Database (Denmark)

    Nølke, Henning

    2009-01-01

    Artiklen præsenterer en teoretisk og empirisk undersøgelse af diskursindividdernes  (DI) natur i et forsøg på bedre at forstå hvilken rolle de spiller i den konkrete tolkning af teksters polyfoni. DI er et centralt element i Den Skandinaviske Polyfoniteori (ScaPoLine). Først introduceres den gene...

  7. Gly118Asp is a SCA14 founder mutation in the Dutch ataxia population

    NARCIS (Netherlands)

    Verbeek, DS; van de Warrenburg, BPC; Hennekam, FAM; Dooijes, D; Ippel, PF; Verschuuren-Bemelmans, CC; Kremer, HPH; Sinke, RJ

    Missense mutations in the PRKCG gene have recently been identified in spinocerebellar ataxia 14 (SCA14) patients; these include the Gly118Asp mutation that we found in a large Dutch autosomal dominant cerebellar ataxia (ADCA) family. We subsequently screened the current Dutch ataxia cohort

  8. Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts

    DEFF Research Database (Denmark)

    Cornelius, Nanna; Wardman, Jonathan H; Hargreaves, Iain P

    2017-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the ataxin-2 gene. We show increased oxidative stress, abnormalities in the antioxidant system, changes in complexes involved in oxidative phosphorylation and changes in mitochondrial...

  9. Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2)

    NARCIS (Netherlands)

    Rueb, U.; Farrag, K.; Seidel, K.; Brunt, E. R.; Heinsen, H.; Buerk, K.; Melegh, B.; von Gall, C.; Auburger, G.; Bohl, J.; Korf, H. W.; Hoche, F.; den Dunnen, W.

    2013-01-01

    Aims: Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of

  10. Exploration of CAG triplet repeat in nontranslated region of SCA12 ...

    Indian Academy of Sciences (India)

    linkage disequilibrium information from Indian Genome Vari- ation Database for mapping mutations: SCA12 case study. J. Genet. 88, 55–60. Brussino A., Graziano C., Giobbe D., Ferrone M., Dragone E.,. Arduino C. et al. 2010 Spinocerebellar ataxia type 12 identified in two Italian families may mimic sporadic ataxia. Mov.

  11. SCA1 patients may present as hereditary spastic paraplegia and must be included in spastic-ataxias group.

    Science.gov (United States)

    Pedroso, José Luiz; de Souza, Paulo Victor Sgobbi; Pinto, Wladimir Bocca Vieira de Rezende; Braga-Neto, Pedro; Albuquerque, Marcus Vinicius Cristino; Saraiva-Pereira, Maria Luiza; Jardim, Laura Bannach; Barsottini, Orlando Graziani Povoas

    2015-10-01

    The combination of cerebellar ataxia and spasticity is common. However, autosomal dominant genetic diseases presenting with spastic-ataxia are a smaller group. Pyramidal signs have been frequently observed in several SCA subtypes, particularly in spinocerebellar ataxia type 1. We prospectively evaluated the pyramidal signs and spasticity in SCA1 patients, and correlated the data with genetic and clinical features. In this study, we observed that spasticity may be an early and presenting feature of SCA1, since 3 patients had pyramidal signs and spasticity as the first neurological sign. SCA1 patients with spasticity were significantly younger. SCA1 may rarely present with pure spastic paraplegia, resembling hereditary spastic paraplegia, before the appearance of cerebellar signs. This observation may confuse the neurologist when a genetic testing is requested for an autosomal dominant spastic paraplegia, directing research to hereditary spastic paraplegia group. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Principal Component Analysis of Cerebellar Shape on MRI Separates SCA Types 2 and 6 into Two Archetypal Modes of Degeneration

    Science.gov (United States)

    Jung, Brian C.; Choi, Soo I.; Du, Annie X.; Cuzzocreo, Jennifer L.; Geng, Zhuo Z.; Ying, Howard S.; Perlman, Susan L.; Toga, Arthur W.; Prince, Jerry L.

    2014-01-01

    Although “cerebellar ataxia” is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes. PMID:22258915

  13. Macular dysfunction and morphology in spinocerebellar ataxia type 7 (SCA 7).

    Science.gov (United States)

    Hugosson, Therése; Gränse, Lotta; Ponjavic, Vesna; Andréasson, Sten

    2009-03-01

    To characterize the clinical phenotype regarding retinal function and macular appearance in patients with spinocerebellar ataxia type 7 (SCA 7), with an emphasis on electrophysiological findings. Three patients from two Swedish families were given an ophthalmological examination including visual acuity, fundus inspection, Farnsworth's color vision test, Goldmann perimetry, full-field electroretinography (full-field ERG), multifocal electroretinography (mfERG) and optical coherence tomography (OCT). DNA was analyzed with polymerase chain reaction for CAG trinucleotide expansion repeats in the SCA 7 gene. Molecular analysis demonstrated abnormally expanded CAG repeats in the gene for SCA 7, which encodes the protein ataxin-7, thus confirming the diagnosis SCA 7. In the oldest patient very discreet pigmentary changes in the maculae were found, but with that exception the patients had a normal ophthalmoscopic fundus appearance and OCT demonstrated only minor changes. MfERG indicated predominantly central involvement, especially in the early disease stages, which in pace with disease progression extended from the center to the more peripheral areas. Full-field ERG in the oldest patient demonstrated bilaterally distinctly prolonged 30-Hz flicker implicit time, verifying widespread cone photoreceptor degeneration. The patients with genetically confirmed SCA 7 presented an early macular dysfunction, preceding any signs of abnormalities in fundus appearance. According to the electrophysiological findings the primary dysfunction involves the cone photoreceptors in the foveal region, however in an older patient involvement of cone photoreceptors throughout the retina was verified. This is in accordance with the theory that ataxin-7 interacts with CRX transcription, since it is known that mutations in the CRX gene cause cone-rod dystrophy.

  14. Distinct cerebellar regions related to motor and cognitive performance in SCA6 patients.

    Science.gov (United States)

    Rentiya, Zubir; Khan, Noore-Sabah; Ergun, Ezgi; Ying, Sarah H; Desmond, John E

    2017-10-31

    To demonstrate a correlation between anatomic regional changes in Spinocerebellar Ataxia type 6 (SCA6) patients and measures of cognitive performance on neuropsychological tests. Neurocognitive testing was conducted on 24 SCA6 and 28 control subjects. For each cognitive test, SCA6 patients were compared against the controls using Student's t-test. For the cerebellar patients, using voxel based morphometry, correlations between cerebellar gray matter volume at each voxel and performance on the neuropsychological exams were calculated using the Pearson correlation coefficient implemented in SPM8. Compared to controls, SCA6 patients exhibited significantly impaired performance on the following cognitive tests: Rey-Auditory Verbal Learning Test Trial V, Controlled Oral Word Association phonemic test and semantic-verb test, Rey-Osterrieth Complex Figure copy test as well as immediate and delayed visuo-spatial memory recall test, Trail Making Test (TMT) Part A and Part B, Stroop Color Task completion time, Stroop Color-Word Task score, and Grooved Pegboard Test (GPT) Dominant and Non-Dominant Hand time. Correlations of gray matter density with cognitive test performance were determined for all SCA6 subjects. Using a p-value threshold of 0.001 and family-wise small volume error correction, significant correlations were found for GPT Non-Dominant, GPT Dominant, TMT Part A, and TMT Part B. Different regional patterns of cerebellar involvement were found for the motoric GPT task and the executive version of the TMT. The results for the GPT strongly indicated that the integrity of medial superior hemispheric regions was associated with motor task performance, whereas executive cognitive function was localized in distinctly different inferior regions. This is the first VBM study to differentiate cognitive and motor contributions of the cerebellum. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Interfacing Sca-1pos Mesenchymal Stem Cells with Biocompatible Scaffolds with Different Chemical Composition and Geometry

    OpenAIRE

    Forte, G.; Franzese, O.; Pagliari, S; Pagliari, F.; A. M. Di Francesco; Cossa, P.; Laudisi, A; Fiaccavento, R.; Minieri, M.; Bonmassar, E.; Di Nardo, P

    2009-01-01

    An immortalized murine mesenchymal stem cell line (mTERT-MSC) enriched for Linneg/Sca-1pos fraction has been obtained through the transfection of MSC with murine TERT and single-cell isolation. Such cell line maintained the typical MSC self-renewal capacity and continuously expressed MSC phenotype. Moreover, mTERT-MSC retained the functional features of freshly isolated MSC in culture without evidence of senescence or spontaneous differentiation events. Thus, mTERT-MSC have been cultured onto...

  16. SL-ST Software Configuration and Management System (SCaM) Project - Project Evaluation Report

    CERN Document Server

    Bartolomé, R; Hatziangeli, Eugenia; Last, I; Ninin, P; Sobczak, H; CERN. Geneva. SPS and LEP Division

    1998-01-01

    This document is the output of the evaluation work done as part of the survey phase of the SCaM project. It contains the evaluation of commercial Software Configuration Mangement tools against previou sly captured User Requirements. Recommendations regarding the best solution are made by the project team. They will serve as a basis for the implementation of a software configuration management syste m and the derivation of a software configuration management procedure for SL and ST.

  17. Extensive White Matter Alterations and Its Correlations with Ataxia Severity in SCA 2 Patients

    Science.gov (United States)

    Hernandez-Castillo, Carlos R.; Galvez, Victor; Mercadillo, Roberto; Diaz, Rosalinda; Campos-Romo, Aurelio; Fernandez-Ruiz, Juan

    2015-01-01

    Background Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo. Methods Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patient's ataxia impairment. Results Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle. Conclusion Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2. PMID:26263162

  18. Extensive White Matter Alterations and Its Correlations with Ataxia Severity in SCA 2 Patients.

    Directory of Open Access Journals (Sweden)

    Carlos R Hernandez-Castillo

    Full Text Available Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo.Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA and mean diffusivity (MD. Significant diffusion differences were correlated with the patient's ataxia impairment.Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle.Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2.

  19. Mesenchymal stem cells ameliorate cerebellar pathology in a mouse model of spinocerebellar ataxia type 1.

    Science.gov (United States)

    Matsuura, Serina; Shuvaev, Anton N; Iizuka, Akira; Nakamura, Kazuhiro; Hirai, Hirokazu

    2014-06-01

    Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disorder caused by the expansion of a polyglutamine tract in the ataxin-1 protein. To date, no fundamental treatments for SCA1 have been elucidated. However, some studies have shown that mesenchymal stem cells (MSCs) are partially effective in other genetic mouse models of cerebellar ataxia. In this study, we tested the efficacy of the intrathecal injection of MSCs in the treatment of SCA1 in transgenic (SCA1-Tg) mice. We found that intrathecal injection of only 3 × 10(3) MSCs greatly mitigated the cerebellar neuronal disorganization observed in SCA1 transgenic mice (SCA1-Tg mice). Although the Purkinje cells (PCs) of 24-week-old nontreated SCA1-Tg mice displayed a multilayer arrangement, SCA1-Tg mice at a similar age injected with MSCs displayed monolayer PCs. Furthermore, intrathecal injection of MSCs suppressed the atrophy of PC dendrites in SCA1-Tg mice. Finally, behavioral tests demonstrated that MSCs normalized deficits in motor coordination in SCA1-Tg mice. Future studies should be performed to develop optimal protocols for intrathecal transplantation of MSCs in SCA1 model primates with the aim of developing applications for SCA1 patients.

  20. Trinucleotide repeat expansion of spinocerebellar ataxia (SCA1) found in a Chinese family.

    Science.gov (United States)

    Cai, T; Yu, P; Chen, X; Lopa, M

    1998-02-01

    To investigate the gene mutation and the ratio of the spinocerebellar ataxia type 1 (SCA1) in Chinese patients with autosomal dominant spinocerebellar ataxia (ADSCA). The family material and DNA samples were collected from thirteen families with ADSCA. To determine the characteristics of the CAG trinucleotide repeats in SCA1 gene, the PCR products of the Rep1 and Rep2 primers were analyzed, and the bands with CAG repeat expansion were cloned by PCR2. 1 vector and sequenced. One family was found to have an expanded CAG repeat in the 13 families with ADSCA. The clinically affected individual was heterozygous with one disease allele being 55 CAG repeats, whereas the mean size of the CAG repeats on 104 chromosomes generated from unrelated control Chinese individuals is 29.3 (ranging from 18 to 34). The frequency of the SCA1 mutation is about 7% in the 13 Chinese families with ADSCA, suggesting that this type of genetic defect is not the main cause involved in the pathogenesis of ADSCA in China. Since the mutation has also been found in Caucasian, Japanese, Malaysian, and Bangladeshi kindreds, it is suggested that this genetic defect may well have multiple origins in different ethnic groups.

  1. Resolution of unique Sca-1highc-Kit- lymphoid-biased progenitors in adult bone marrow.

    Science.gov (United States)

    Harman, Benjamin C; Northrup, Daniel L; Allman, David

    2008-12-01

    We have identified a distinctive lymphoid-restricted progenitor population in adult mouse bone marrow based on a unique c-Kit(-)Sca-1(high)Flt3(+) AA4(+) surface phenotype. These cells are highly lymphoid biased and rapidly generate B and T cells after adoptive transfer. However, whereas previously described lymphoid progenitors such as common lymphoid progenitors express TdT and relatively high levels of RAG2, and are enriched for cells with an active V(D)J recombinase, Flt3(+) AA4(+) cells within the c-Kit(-)Sca-1(high) bone marrow fraction are TdT(-), are RAG2(low), and do not display evidence for ongoing or past recombinase activity. Furthermore, unlike common lymphoid progenitors that readily generate B cells upon stimulation with IL-7, c-Kit(-)Sca-1(high)Flt3(+) precursors do not express abundant levels of the IL-7R, and require costimulation with Flt3 ligand and IL-7 to generate B cells in vitro. Moreover, these findings suggest that hematopoietic stem cells in adults generate an array of lymphoid-biased progenitor populations characterized by distinct gene expression and cytokine response profiles.

  2. Isolation, screening and partial purification of antimicrobial antibiotics from soil Streptomyces sp. SCA 7

    Directory of Open Access Journals (Sweden)

    P. Saravana Kumar

    2014-09-01

    Full Text Available Thirty-seven actinomycetes strains were isolated from soil samples collected from an agriculture field in Vengodu, Thiruvannamalai District, Tamil Nadu, India (latitude: 12° 54′ 0033″, North; longitude: 79° 78′ 5216″, East; elevation: 228.6/70.0 ft/m. The isolates were assessed for antagonistic activity against five Gram-positive bacteria, seven Gram-negative bacteria, and two pathogenic fungi. During the initial screening, 43% of the strains showed weak activity, 16% showed moderate activity, 5% showed good activity, and 35% showed no antagonistic activity. Among the strains tested, SCA 7 showed strong antimicrobial activity. Maximum biological activity was obtained on modified nutrient glucose agar (MNGA medium. The mycelia of SCA 7 were extracted with methanol and tested against microbial pathogens using the disc diffusion method. The crude extract was purified partially using column chromatography and assessed for antimicrobial activity. Fraction 10 showed good activity against Staphylococcus epidermidis (31.25 μg/mL and Malassezia pachydermatis (500 μg/mL and the active principle (fraction 10 was identified as 2,4-bis (1,1-dimethylethyl phenol. Based on morphological, physiological, biochemical, cultural, and molecular characteristics (16S rDNA sequencing, this strain was identified as Streptomyces sp. SCA 7. It could be used in the development of new substances for pharmaceutical or agricultural purposes.

  3. TXRF analysis of multielements in serum of patients with sickle cell anemia (SCA) by synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Canellas, Catarine G.L.; Jesus, Edgar F.O. de; Anjos, Marcelino J.; Lopes, Ricardo T., E-mail: catarine@lin.ufrj.b, E-mail: edgar@lin.ufrj.b, E-mail: marcelin@lin.ufrj.b, E-mail: ricardo@lin.ufrj.b [Federal University of Rio de Janeiro (UFRJ), RJ (Brazil). COPPE Technology Center. Nuclear Instrumentation Lab.; Carvalho, Silvia M.F., E-mail: silvia@hemorio.rj.gov.b [State Institute of Hematology Arthur de Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, RJ (Brazil)

    2009-07-01

    The determination of trace elements levels in physiological fluids is of considerable interest in clinical chemistry. Since it has been established these levels in human serum can be utilized as indicators for several pathological conditions, diagnosis and treatment of various diseases. In this work, trace elements were analyzed in serum of patients with sickle cell anemia (SCA) by total reflection X-ray fluorescence using synchrotron radiation (SRTXRF). Sickle cell Anemia is a blood disorder that affects hemoglobin, the protein found in red blood cells that help carry oxygen throughout the body. SCA occurs when a person inherits two abnormal genes (one from each parent) that cause their red blood cells to change shape. These irregular-shaped blood cells die prematurely, resulting in a chronic shortage of red blood cells. We studied forty-three patients (15 males and 28 females) aged 18 to 50 years, suffering SCA and Sixty healthy volunteers (41 males and 19 females) aged 18 to 60 years. All the serum samples had been collected of people who live in the urban area of Rio de Janeiro City/Brazil. The measurements were performed at the X-ray fluorescence beam line at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo using a polychromatic beam. It was possible to determine the concentrations of the following elements: P, S, Cl, K, Ca, Cu, Zn, Br and Rb. (author)

  4. Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms.

    Science.gov (United States)

    Paciorkowski, A R; Shafrir, Y; Hrivnak, J; Patterson, M C; Tennison, M B; Clark, H B; Gomez, C M

    2011-09-13

    To provide clinical data on a cohort of 6 patients with massive expansion (>200 CAG repeats) of spinocerebellar ataxia type 2 (SCA2) and investigate possible pathways of pathogenesis using bioinformatics analysis of ATXN2 networks. We present data on 6 patients with massive expansion of SCA2 who presented in infancy with variable combinations of hypotonia, global developmental delay, infantile spasms, and retinitis pigmentosa. ATXN2 is known to interact with a network of synaptic proteins. To investigate pathways of pathogenesis, we performed bioinformatics analysis on ATXN2 combined with known genes associated with infantile spasms, retinitis pigmentosa, and synaptic function. All patients had a progressive encephalopathy with autonomic dysfunction, 4 had retinitis pigmentosa, and 3 had infantile spasms. The bioinformatics analysis led to several interesting findings. First, an interaction between ATXN2 and SYNJ1 may account for the development of retinitis pigmentosa. Second, dysfunction of postsynaptic vesicle endocytosis may be important in children with this progressive encephalopathy. Infantile spasms may be associated with interactions between ATXN2 and the postsynaptic structural proteins MAGI2 and SPTAN1. Severe phenotype in children with massive expansion of SCA2 may be due to a functional deficit in protein networks in the postsynapse, specifically involving vesicle endocytosis.

  5. Amplio espectro fenotípico de la SCA-3: paraparesia espástica hereditaria

    Directory of Open Access Journals (Sweden)

    Sergio A. Rodríguez-Quiroga

    2013-12-01

    Full Text Available La ataxia espinocerebelosa tipo 3 o enfermedad de Machado-Joseph (SCA-3/EMJ es la forma más frecuente de ataxia espinocerebelosa autosómica dominante. Se caracteriza por una marcada variabilidad fenotípica, pudiendo causar formas no cerebelosas de presentación. En base a algunos casos comunicados, se ha propuesto una forma de presentación clínica similar a la de una paraparesia espástica hereditaria, con la presencia de signos de disfunción piramidal predominantes como la manifestación clínica inicial. Presentamos dos nuevos casos de SCA-3/EMJ con un cuadro clínico inicial sugerente de paraparesia espástica hereditaria y una revisión de los casos clínicos similares previamente informados. Nuestros hallazgos apoyan la propuesta de un subtipo de SCA-3/EMJ caracterizado por la presencia de marcada disfunción piramidal como manifestación inicial, simulando un cuadro clínico de paraparesia espástica hereditaria.

  6. Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue

    OpenAIRE

    Patricia E Burger; Xiong, Xiaozhong; Coetzee, Sandra; Salm, Sarah N.; Moscatelli, David; Goto, Ken; Wilson, E. Lynette

    2005-01-01

    We previously showed that prostatic stem cells are concentrated in the proximal regions of prostatic ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of ducts was more effective in generating prostatic tissue than a comparable populat...

  7. Improve the prevention of sudden cardiac arrest in emerging countries: the Improve SCA clinical study design.

    Science.gov (United States)

    Zhang, Shu; Singh, Balbir; Rodriguez, Diego A; Chasnoits, Alexandr Robertovich; Hussin, Azlan; Ching, Chi-Keong; Huang, Dejia; Liu, Yen-Bin; Cerkvenik, Jeffrey; Willey, Sarah; Kim, Young-Hoon

    2015-11-01

    This study aims to demonstrate that primary prevention (PP) patients with one or more additional risk factors are at a similar risk of life-threatening ventricular arrhythmias when compared with secondary prevention (SP) patients, and would receive similar benefit from an implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy-defibrillator (CRT-D) implant. The study evaluates the benefits of therapy for high-risk patients in countries where defibrillation therapy for PP of SCA is underutilized. Enrolment will consist of 4800 ICD-eligible patients from Asia, Latin America, Eastern Europe, the Middle East, and Africa. Upon enrolment, patients will be categorized as SP or PP. Primary prevention patients will be assessed for additional risk factors: syncope/pre-syncope, non-sustained ventricular tachycardia, frequent premature ventricular contractions, and low left ventricular ejection fraction. Those PP patients with one or more risk factors will be categorized as '1.5' patients. Implant of an ICD/CRT-D will be left to the patient and/or physician's discretion. The primary endpoint will compare the appropriate ICD therapy rate between SP and 1.5 patients. The secondary endpoint compares mortality between 1.5 implanted and non-implanted patients. The Improve SCA study will investigate a subset of PP patients, believed to be at similar risk of life-threatening ventricular arrhythmias as SP patients. Results may help clinicians identify and refer the highest risk PP patients for ICDs, help local societies expand guidelines to include PP of SCA utilizing ICDs, and provide additional geographical-relevant evidence to allow patients to make an informed decision whether to receive an ICD. NCT02099721. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  8. Gene clusters located on two large plasmids determine spore crystal association (SCA) in Bacillus thuringiensis subsp. finitimus strain YBT-020.

    Science.gov (United States)

    Zhu, Yiguang; Ji, Fang; Shang, Hui; Zhu, Qian; Wang, Pengxia; Xu, Chengchen; Deng, Yun; Peng, Donghai; Ruan, Lifang; Sun, Ming

    2011-01-01

    Crystals in Bacillus thuringiensis are usually formed in the mother cell compartment during sporulation and are separated from the spores after mother cell lysis. In a few strains, crystals are produced inside the exosporium and are associated with the spores after sporulation. This special phenotype, named 'spore crystal association' (SCA), typically occurs in B. thuringiensis subsp. finitimus. Our aim was to identify genes determining the SCA phenotype in B. thuringiensis subsp. finitimus strain YBT-020. Plasmid conjugation experiments indicated that the SCA phenotype in this strain was tightly linked with two large plasmids (pBMB26 and pBMB28). A shuttle bacterial artificial chromosome (BAC) library of strain YBT-020 was constructed. Six fragments from BAC clones were screened from this library and discovered to cover the full length of pBMB26; four others were found to cover pBMB28. Using fragment complementation testing, two fragments, each of approximately 35 kb and located on pBMB26 and pBMB28, were observed to recover the SCA phenotype in an acrystalliferous mutant, B. thuringiensis strain BMB171. Furthermore, deletion analysis indicated that the crystal protein gene cry26Aa from pBMB26, along with five genes from pBMB28, were indispensable to the SCA phenotype. Gene disruption and frame-shift mutation analyses revealed that two of the five genes from pBMB28, which showed low similarity to crystal proteins, determined the location of crystals inside the exosporium. Gene disruption revealed that the three remaining genes, similar to spore germination genes, contributed to the stability of the SCA phenotype in strain YBT-020. Our results thus identified the genes determining the SCA phenotype in B. thuringiensis subsp. finitimus.

  9. Gene clusters located on two large plasmids determine spore crystal association (SCA in Bacillus thuringiensis subsp. finitimus strain YBT-020.

    Directory of Open Access Journals (Sweden)

    Yiguang Zhu

    Full Text Available Crystals in Bacillus thuringiensis are usually formed in the mother cell compartment during sporulation and are separated from the spores after mother cell lysis. In a few strains, crystals are produced inside the exosporium and are associated with the spores after sporulation. This special phenotype, named 'spore crystal association' (SCA, typically occurs in B. thuringiensis subsp. finitimus. Our aim was to identify genes determining the SCA phenotype in B. thuringiensis subsp. finitimus strain YBT-020. Plasmid conjugation experiments indicated that the SCA phenotype in this strain was tightly linked with two large plasmids (pBMB26 and pBMB28. A shuttle bacterial artificial chromosome (BAC library of strain YBT-020 was constructed. Six fragments from BAC clones were screened from this library and discovered to cover the full length of pBMB26; four others were found to cover pBMB28. Using fragment complementation testing, two fragments, each of approximately 35 kb and located on pBMB26 and pBMB28, were observed to recover the SCA phenotype in an acrystalliferous mutant, B. thuringiensis strain BMB171. Furthermore, deletion analysis indicated that the crystal protein gene cry26Aa from pBMB26, along with five genes from pBMB28, were indispensable to the SCA phenotype. Gene disruption and frame-shift mutation analyses revealed that two of the five genes from pBMB28, which showed low similarity to crystal proteins, determined the location of crystals inside the exosporium. Gene disruption revealed that the three remaining genes, similar to spore germination genes, contributed to the stability of the SCA phenotype in strain YBT-020. Our results thus identified the genes determining the SCA phenotype in B. thuringiensis subsp. finitimus.

  10. Amplio espectro fenotípico de la SCA-3: paraparesia espástica hereditaria

    OpenAIRE

    Sergio A. Rodríguez-Quiroga; Dolores González-Morón; Tomoko Arakaki; Nélida Garreto; Marcelo A. Kauffman

    2013-01-01

    La ataxia espinocerebelosa tipo 3 o enfermedad de Machado-Joseph (SCA-3/EMJ) es la forma más frecuente de ataxia espinocerebelosa autosómica dominante. Se caracteriza por una marcada variabilidad fenotípica, pudiendo causar formas no cerebelosas de presentación. En base a algunos casos comunicados, se ha propuesto una forma de presentación clínica similar a la de una paraparesia espástica hereditaria, con la presencia de signos de disfunción piramidal predominantes como la manifestación clíni...

  11. Mesial temporal lobe epilepsy in a patient with spinocerebellar ataxia type 13 (SCA13).

    Science.gov (United States)

    Bürk, Katrin; Strzelczyk, Adam; Reif, Philipp S; Figueroa, Karla P; Pulst, Stefan M; Zühlke, Christine; Oertel, Wolfgang H; Hamer, Hajo M; Rosenow, Felix

    2013-04-01

    We report a female patient of German descent with a molecular diagnosis of SCA13 who presented with a history of cerebellar ataxia and epilepsy. The underlying mutation R420H had been shown to cause a dominant negative effect on the functional properties of the voltage-gated potassium channel KCNC3. Despite widespread KCNC3 expression in the central nervous system, the patient presented with a left mesiotemporal electroencephalogram focus and left hippocampal sclerosis. This is the first case, which reports an association between mesial temporal lobe epilepsy and spinocerebellar ataxia type 13. This demonstrates that epilepsy of structural-metabolic cause may be contingent upon genetically defined channelopathies.

  12. GPS and Galileo Developments on Board the International Space Station With the Space Communications and Navigation (SCaN) Testbed

    Science.gov (United States)

    Pozzobon, Oscar; Fantinato, Samuele; Dalla Chiara, Andrea; Gamba, Giovanni; Crisci, Massimo; Giordana, Pietro; Enderle, Werner; Chelmins, David; Sands, Obed S.; Clapper, Carolyn J.; hide

    2016-01-01

    The Space Communications and Navigation (SCaN) is a facility developed by NASA and hosted on board the International Space Station (ISS) on an external truss since 2013.It has the objective of testing navigation and communication experimentations with a Software Defined Radio (SDR) approach, which permits software updates for testing new experimentations.NASA has developed the Space Telecommunications Radio System (STRS) architecture standard for SDRs used in space and ground-based platforms to provide commonality among radio developments to provide enhanced capability. The hardware is equipped with both L band front-end radios and the NASA space network communicates with it using S-band, Ku-band and Ka-band links.In May 2016 Qascom started GARISS (GPS and Galileo Receiver for the ISS), an activity of experimentation in collaboration with ESA and NASA that has the objective to develop and validate the acquisition and processing of combined GPS and Galileo signals on board the ISS SCaN testbed. This paper has the objective to present the mission, and provide preliminary details about the challenges in the design, development and verification of the waveform that will be installed on equipment with limited resources. GARISS is also the first attempt to develop a waveform for the ISS as part of an international collaboration between US and Europe. Although the final mission objective is to target dual frequency processing, initial operations will foresee a single frequency processing. Initial results and trade-off between the two options, as well as the final decision will be presented and discussed. The limited resources on board the SCaN with respect to the challenging requirements to acquire and track contemporaneously two satellite navigation systems, with different modulations and data structure, led to the need to assess the possibility of aiding from ground through the S-band. This option would allow assistance to the space receiver in order to provide

  13. Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

    Directory of Open Access Journals (Sweden)

    Rui Gao

    2015-01-01

    Full Text Available Spinocerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease (MJD, is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-δ pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers

  14. Genetic mutation, linkage and heterogeneity analysis in Spanish pedigrees and isolated cases of autosomal dominant spinocerebellar ataxia (SCA)

    Energy Technology Data Exchange (ETDEWEB)

    Volpini, V.; Matilla, T.; Genis, D. [Institut de Recerca Oncologica, Barcelona (Spain)] [and others

    1994-09-01

    We report a genetic study of 14 Spanish kindreds and 11 isolated cases with SCA. The diagnosis was ascertained in 60 members, but clinical data were only obtained for 35 of them. One defective gene responsible for the disease was localized to 6p22-p23 (SCA1) and the mutation consists of an expansion of an intragenic (CAG){sub n} repeat (REP). We studied all of our genealogical and isolated affected individuals in order to know their 6p mutational status. Thus we detected a large pedigree which has the pathological expansion with {open_quotes}n{close_quotes} in the range of 41 to 57 repeats. The expansion increases through generations and correlates with anticipation. In the Spanish population, the non-pathological range of {open_quotes}n{close_quotes} is from 6 to 39 repeats. These sequences are {open_quotes}protected{close_quotes} having an interrupted repeat configuration, studied by restriction and sequencing analysis. This mutation was not present in the genealogical or isolated affected individuals studied. We also tested our families with the recently reported CAG expansion in 12p-12ter (DRPLA) and obtained negative results. Linkage analysis in non-SCA1, DRPLA families using markers from others chromosomal regions, 12q23-24.1 (SCA2) and 14q24.3-q32 (SCA3), results in negative lod scores and shows genetic heterogeneity in our population.

  15. Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2.

    Science.gov (United States)

    Pflieger, Lance T; Dansithong, Warunee; Paul, Sharan; Scoles, Daniel R; Figueroa, Karla P; Meera, Pratap; Otis, Thomas S; Facelli, Julio C; Pulst, Stefan M

    2017-08-15

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice versus wild-type (WT) littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes. Our analysis revealed previously uncharacterized early and progressive abnormal patterning of cerebellar gene expression. Weighted Gene Coexpression Network Analysis revealed four gene modules that were significantly correlated with disease status, composed primarily of genes associated with GTPase signaling, calcium signaling and cell death. Of these genes, few overlapped with differentially expressed cerebellar genes that we identified in Atxn2-/- knockout mice versus WT littermates, suggesting that loss-of-function is not a significant component of disease pathology. We conclude that SCA2 is a disease characterized by gain of function for ATXN2. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Interfacing Sca-1pos Mesenchymal Stem Cells with Biocompatible Scaffolds with Different Chemical Composition and Geometry

    Directory of Open Access Journals (Sweden)

    G. Forte

    2009-01-01

    Full Text Available An immortalized murine mesenchymal stem cell line (mTERT-MSC enriched for Linneg/Sca-1pos fraction has been obtained through the transfection of MSC with murine TERT and single-cell isolation. Such cell line maintained the typical MSC self-renewal capacity and continuously expressed MSC phenotype. Moreover, mTERT-MSC retained the functional features of freshly isolated MSC in culture without evidence of senescence or spontaneous differentiation events. Thus, mTERT-MSC have been cultured onto PLA films, 30 and 100 μm PLA microbeads, and onto unpressed and pressed HYAFF-11 scaffolds. While the cells adhered preserving their morphology on PLA films, clusters of mTERT-MSC were detected on PLA beads and unpressed fibrous scaffolds. Finally, mTERT-MSC were not able to colonize the inner layers of pressed HYAFF-11. Nevertheless, such cell line displayed the ability to preserve Sca-1 expression and to retain multilineage potential when appropriately stimulated on all the scaffolds tested.

  17. Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation

    DEFF Research Database (Denmark)

    Bech, Sara; Petersen, Thor; Nørremølle, Anne

    2010-01-01

    tract in the respective proteins. SCA17 is caused by a CAG/CAA repeat expansion in the TATA box-binding protein-gene (TBP). In some cases the clinical phenotype of SCA17 overlaps that of Huntington's disease (HD), hence the use of the term Huntington's disease-like. We screened 89 patients...... with a Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats....... The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington's disease...

  18. Long Term Performance Metrics of the GD SDR on the SCaN Testbed: The First Year on the ISS

    Science.gov (United States)

    Nappier, Jennifer; Wilson, Molly C.

    2014-01-01

    The General Dynamics (GD) S-Band software defined radio (SDR) in the Space Communications and Navigation (SCaN) Testbed on the International Space Station (ISS) provides experimenters an opportunity to develop and demonstrate experimental waveforms in space. The SCaN Testbed was installed on the ISS in August of 2012. After installation, the initial checkout and commissioning phases were completed and experimental operations commenced. One goal of the SCaN Testbed is to collect long term performance metrics for SDRs operating in space in order to demonstrate long term reliability. These metrics include the time the SDR powered on, the time the power amplifier (PA) is powered on, temperature trends, error detection and correction (EDAC) behavior, and waveform operational usage time. This paper describes the performance of the GD SDR over the first year of operations on the ISS.

  19. c-Myb Regulates Proliferation and Differentiation of Adventitial Sca1+ Vascular Smooth Muscle Cell Progenitors by Transactivation of Myocardin.

    Science.gov (United States)

    Shikatani, Eric A; Chandy, Mark; Besla, Rickvinder; Li, Cedric C; Momen, Abdul; El-Mounayri, Omar; Robbins, Clinton S; Husain, Mansoor

    2016-07-01

    Vascular smooth muscle cells (VSMCs) are believed to dedifferentiate and proliferate in response to vessel injury. Recently, adventitial progenitor cells were implicated as a source of VSMCs involved in vessel remodeling. c-Myb is a transcription factor known to regulate VSMC proliferation in vivo and differentiation of VSMCs from mouse embryonic stem cell-derived progenitors in vitro. However, the role of c-Myb in regulating specific adult vascular progenitor cell populations was not known. Our objective was to examine the role of c-Myb in the proliferation and differentiation of Sca1(+) adventitial VSMC progenitor cells. Using mice with wild-type or hypomorphic c-myb (c-myb(h/h)), BrdU (bromodeoxyuridine) uptake and flow cytometry revealed defective proliferation of Sca1(+) adventitial VSMC progenitor cells at 8, 14, and 28 days post carotid artery denudation injury in c-myb(h/h) arteries. c-myb(h/h) cKit(+)CD34(-)Flk1(-)Sca1(+)CD45(-)Lin(-) cells failed to proliferate, suggesting that c-myb regulates the activation of specific Sca1(+) progenitor cells in vivo and in vitro. Although expression levels of transforming growth factor-β1 did not vary between wild-type and c-myb(h/h) carotid arteries, in vitro differentiation of c-myb(h/h) Sca1(+) cells manifested defective transforming growth factor-β1-induced VSMC differentiation. This is mediated by reduced transcriptional activation of myocardin because chromatin immunoprecipitation revealed c-Myb binding to the myocardin promoter only during differentiation of Sca1(+) cells, myocardin promoter mutagenesis identified 2 specific c-Myb-responsive binding sites, and adenovirus-mediated expression of myocardin rescued the phenotype of c-myb(h/h) progenitors. These data support a role for c-Myb in the regulation of VSMC progenitor cells and provide novel insight into how c-myb regulates VSMC differentiation through myocardin. © 2016 American Heart Association, Inc.

  20. Mapping of the Sca1 and pcd genes on mouse chromosome 13 provides evidence that they are different genes

    Energy Technology Data Exchange (ETDEWEB)

    Servadio, A.; McCall, A.; Zoghbi, H. [Baylor College of Medicine, Houston, TX (United States); Eicher, E.M. [Jackson Laboratory, Bar Harbor, ME (United States)

    1995-10-10

    It is well established that large chromosomal segments have remained intact during the evolution of different mammalian species. Thus, mapping information for a gene in mammalian species facilitates mapping the same gene in another mammalian species. In addition, phenotypically similar diseases that map to linkage conserved regions in two species may be caused by mutations in the same gene. Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited human disorder characterized by progressive ataxia, dysarthria, and dysmetria. SCA1 maps to the short arm of human chromosome (Chr) 6 in the 6p23-p22 region. SCA1 is caused by the expansion of an unstable CAG repeat located within the coding region of a novel protein, ataxin-1, Purkinje cell degeneration (pcd) is a recessively inherited mouse disorder characterized by a moderate ataxia, usually noted by 3-4 weeks of age. Progressive degeneration of Purkinje cells is the underlying pathogenesis in this disorder. The pcd gene was assigned to mouse Chr 13 because it showed linkage to extra toes (Xt) and pearl (pe). Some doubt about this assignment existed, however, because the calculated genetic distance between pcd and Xt was 32 cM and that between pcd and pe was 18 cM. If pcd is located in Chr 13, its placement relative to Xt and pe suggests that it would be located in the region that shares linkage homology with the region that shares linkage homology with the region of human Chr 6 that contains SCA1. Here, we present data that confirm the assignment of pcd to Chr 13, map the mouse Sca1 gene to Chr 13, and eliminate Sca1 as a candidate gene for pcd. 11 refs., 1 tab.

  1. Sustainable Competitive Advantage (SCA Analysis of Furniture Manufacturers in Malaysia: Normalized Scaled Critical Factor Index (NSCFI Approach

    Directory of Open Access Journals (Sweden)

    Tasmin Rosmaini

    2016-06-01

    Full Text Available The purpose of this paper is to investigate Malaysian furniture industry via Sustainable competitive advantages (SCA approach. In this case study, sense and respond method and Normalized Scaled Critical Factor Index (NSCFI are used to specify the distribution of companies’ resources for different criteria and detect the attributes which are critical based on expectation and experience of companies’ employs. Moreover, this study evaluates Malaysian furniture business strategy according to manufacturing strategy in terms of analyzer, prospector and defender. Finally, SCA risk levels are presented to show how much company’s resource allocations support their business strategy.

  2. A ScaI RFLP demonstrated for the GRO gene on chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Beck, J.S.; Murray, J.C. (Univ. of Iowa Hospitals, Iowa City (USA)); Sager, R. (Dana Farber Cancer Institute, Boston, MA (USA))

    1989-11-11

    TC870 is a 0.85 kb fragment running from the EcoRI site 200 pb from the 5{prime} end of the human cDNA subcloned into the EcoRI site of pGEM3. ScaI detects a polymorphism with two variable bands of 19 kb and 16 kb. One strong constant band (14 kb) and two fainter constant bands (5 kb and 3 kb) are also present. The polymorphism type is unknown. GRO has been localized to 4q13-4q21 by somatic cell hybrid analysis and in situ hybridization. Codominant segregation and Hardy-Weinberg equilibrium demonstrated in 20 CEPH families. The probe also was assigned to chromosome 4 with significant linkage to ALB, GC, INP10, MT2P1. GRO may be the same gene as MGSA.

  3. Pax7 is necessary and sufficient for the myogenic specification of CD45+:Sca1+ stem cells from injured muscle.

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    Patrick Seale

    2004-05-01

    Full Text Available CD45(+:Sca1(+ adult stem cells isolated from uninjured muscle do not display any myogenic potential, whereas those isolated from regenerating muscle give rise to myoblasts expressing the paired-box transcription factor Pax7 and the bHLH factors Myf5 and MyoD. By contrast, CD45(+:Sca1(+ isolated from injured Pax7( -/- muscle were incapable of forming myoblasts. Infection of CD45(+:Sca1(+ cells from uninjured muscle with retrovirus expressing Pax7 efficiently activated the myogenic program. The resulting myoblasts expressed Myf5 and MyoD and differentiated into myotubes that expressed myogenin and myosin heavy chain. Infection of CD45(-:Sca1(- cells from Pax7( -/- muscle similarly gave rise to myoblasts. Notably, infection of Pax7-deficient muscle with adenoviral Pax7 resulted in the de novo formation of regenerated myofibers. Taken together, these results indicate that Pax7 is necessary and sufficient to induce the myogenic specification of CD45(+ stem cells resident in adult skeletal muscle. Moreover, these experiments suggest that viral transduction of Pax7 is a potential therapeutic approach for the treatment of neuromuscular degenerative diseases.

  4. Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy.

    Science.gov (United States)

    Abdel-Aleem, Alice; Zaki, Maha S

    2008-03-01

    We describe an Egyptian family having SCA2 affecting three generations with marked molecular and clinical anticipation observed in the index case. Our proband was a male child starting as early as 2 years old with progressive extrapyramidal manifestations, slow eye movements and cognitive impairment. A history of nonspecific mild developmental delay was recorded. The patient lost all cognitive functions, had persistent dystonic posture, trophic changes, vasomotor instability, dysphagia and died at the age of 7 years. The age at presentation among other affected family members varied between 11 and 45 years old across three generations. The early common neurological symptoms were choreoathetotic movements, myoclonic jerk, gait difficulty, expressionless face and emotional liability. Later, overt ataxia, incoordination, dysarthria, mild dementia and slow eye saccades predominated. Brisk tendon reflexes were detected in three cases. Peripheral nerve affection was a late manifestation. Interestingly, polyphagia and obesity were striking manifestations in the middle stage of the disease; an observation that might support a previously suggested relation between the ataxin-2 gene and body weight. The proband showed an amplified allele with marked CAG expansion in the form of a smear sized 69-75 repeats resulted from maternal transmission. To our knowledge, our index case is the second report in the literature presenting with infantile onset SCA2 and intermediate repeat expansion. This family expands the phenotypic spectrum of early onset SCA2 and points out the importance of considering SCA2 gene analysis in children with progressive neurological impairment and abnormal movements with or without polyphagia.

  5. SCA1+ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions

    NARCIS (Netherlands)

    Du Pré, Bastiaan C.; Demkes, Evelyne J.; Feyen, Dries A.M.; Dierickx, Pieterjan; Crnko, Sandra; Kok, Bart G. J. M.; Sluijter, Joost P.G.; Doevendans, Pieter A.; Vos, Marc A.; Van Veen, Toon A.B.; Van Laake, Linda W.

    2017-01-01

    Stem cell antigen 1-positive (SCA1+) cells (SPCs) have been investigated in cell-based cardiac repair and pharmacological research, although improved cardiac function after injection has been variable and the mode of action remains unclear. Circadian (24-hr) rhythms are biorhythms regulated by

  6. Cytokines inducing bone marrow SCA+ cells migration into pancreatic islet and conversion into insulin-positive cells in vivo.

    Directory of Open Access Journals (Sweden)

    LuGuang Luo

    Full Text Available We hypothesize that specific bone marrow lineages and cytokine treatment may facilitate bone marrow migration into islets, leading to a conversion into insulin producing cells in vivo. In this study we focused on identifying which bone marrow subpopulations and cytokine treatments play a role in bone marrow supporting islet function in vivo by evaluating whether bone marrow is capable of migrating into islets as well as converting into insulin positive cells. We approached this aim by utilizing several bone marrow lineages and cytokine-treated bone marrow from green fluorescent protein (GFP positive bone marrow donors. Sorted lineages of Mac-1(+, Mac-1(-, Sca(+, Sca(-, Sca(-/Mac-1(+ and Sca(+/Mac-1(- from GFP positive mice were transplanted to irradiated C57BL6 GFP negative mice. Bone marrow from transgenic human ubiquitin C promoter GFP (uGFP, with strong signal C57BL6 mice was transplanted into GFP negative C57BL6 recipients. After eight weeks, migration of GFP positive donor' bone marrow to the recipient's pancreatic islets was evaluated as the percentage of positive GFP islets/total islets. The results show that the most effective migration comes from the Sca(+/Mac(- lineage and these cells, treated with cytokines for 48 hours, were found to have converted into insulin positive cells in pancreatic islets in vivo. This study suggests that bone marrow lineage positive cells and cytokine treatments are critical factors in determining whether bone marrow is able to migrate and form insulin producing cells in vivo. The mechanisms causing this facilitation as well as bone marrow converting to pancreatic beta cells still need to be investigated.

  7. Space Communications and Navigation (SCaN) Integrated Network Architecture Definition Document (ADD). Volume 1; Executive Summary; Revision 1

    Science.gov (United States)

    Younes, Badri A.; Schier, James S.

    2010-01-01

    The SCaN Program has defined an integrated network architecture that fully meets the Administrator s mandate to the Program, and will result in a NASA infrastructure capable of providing the needed and enabling communications services to future space missions. The integrated network architecture will increase SCaN operational efficiency and interoperability through standardization, commonality and technology infusion. It will enable NASA missions requiring advanced communication and tracking capabilities such as: a. Optical communication b. Antenna arraying c. Lunar and Mars Relays d. Integrated network management (service management and network control) and integrated service execution e. Enhanced tracking for navigation f. Space internetworking with DTN and IP g. End-to-end security h. Enhanced security services Moreover, the SCaN Program has created an Integrated Network Roadmap that depicts an orchestrated and coherent evolution path toward the target architecture, encompassing all aspects that concern network assets (i.e., operations and maintenance, sustaining engineering, upgrade efforts, and major development). This roadmap identifies major NASA ADPs, and shows dependencies and drivers among the various planned undertakings and timelines. The roadmap is scalable to accommodate timely adjustments in response to Agency needs, goals, objectives and funding. Future challenges to implementing this architecture include balancing user mission needs, technology development, and the availability of funding within NASA s priorities. Strategies for addressing these challenges are to: define a flexible architecture, update the architecture periodically, use ADPs to evaluate options and determine when to make decisions, and to engage the stakeholders in these evaluations. In addition, the SCaN Program will evaluate and respond to mission need dates for technical and operational capabilities to be provided by the SCaN integrated network. In that regard, the architecture

  8. SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment

    Directory of Open Access Journals (Sweden)

    Genevieve V. Dall

    2017-02-01

    Full Text Available Estrogen stimulates breast development during puberty and mammary tumors in adulthood through estrogen receptor-α (ERα. These effects are proposed to occur via ERα+ luminal cells and not the mammary stem cells (MaSCs that are ERαneg. Since ERα+ luminal cells express stem cell antigen-1 (SCA-1, we sought to determine if SCA-1 could define an ERα+ subset of EpCAM+/CD24+/CD49fhi MaSCs. We show that the MaSC population has a distinct SCA-1+ population that is abundant in pre-pubertal mammary glands. The SCA-1+ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1neg counterparts. However, they express ERα and specifically enter the cell cycle at puberty. Using estrogen-deficient aromatase knockouts (ArKO, we showed that the SCA-1+ MaSC could be directly modulated by estrogen supplementation. Thus, SCA-1 enriches for an ERα+, estrogen-sensitive subpopulation within the CD24+/CD49fhi MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.

  9. Effect of heat treatment on gravity die-cast Sc-A356 aluminium alloy

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    Lim Ying Pio

    2017-01-01

    Full Text Available The effects of scandium addition (0.00 wt.%, 0.2 wt.%, 0.4 wt.% and 0.6 wt.% and T6 heat treatment on the microstructure and mechanical properties of A356 aluminium alloy have been investigated in the research reported in this paper. The Sc inoculated specimens were prepared by gravity die-casting, according to ASTM B557-06 standard. The cast samples were then subjected to heat treatment at solutionizing temperature of 540 °C for 8 h followed by water quenching and artificial aging at 160 °C for 6 h. The microstructure, microhardness and tensile strength of the heat-treated samples were examined with use of scanning electron microscope (SEM, optical microscope, Vicker’s hardness tester, and Instron static machine respectively. Heat treatment was found to be able to effectively reduce grain size down to 16 μm (0.6 wt.% Sc, from 40 μm (original A356. The tensile strength was significantly improved, up to 338 MPa for heat treated 0.6 wt.% Sc-A356 having been achieved. The microhardness of 118 HV has been obtained for heat treated 0.6 wt.%Sc-A356.

  10. Assessment of Socioeconomic Vulnerability to Floods in the Bâsca Chiojdului Catchment Area

    Directory of Open Access Journals (Sweden)

    REMUS PRĂVĂLIE

    2014-12-01

    Full Text Available Hydrological risk phenomena such as floods are among the most costly natural disasters worldwide, effects consisting of socioeconomic damages and deaths. The Bâsca Chiojdului catchment area, by its morphometric and hydrographic peculiarities, is prone to generate these hydrological risk phenomena, so there is a high vulnerability in the socioeconomic elements. This paper is focused on the identification of the main socioeconomic elements vulnerable to hydrological risk phenomena such as floods, based on the assessment of their manifestation potential. Thus, following the delimitation of areas with the highest flood occurrence potential (susceptibility to floods, major socioeconomic factors existing in the basin, considering human settlements (constructions, transport infrastructure, and agricultural areas (the most important category, were superimposed. Results showed a high vulnerability for all three exposed socioeconomic elements especially in valley sectors, of which household structures were the most vulnerable, given both their importance and the high number of areas highly exposed to floods (approximately 2,500 houses and outbuildings, out of a total of about 10,250, intersect the most susceptible area to floods in the study area.

  11. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3.

    NARCIS (Netherlands)

    Verbeek, D.S.; Warrenburg, B.P.C. van de; Wesseling, P.; Pearson, P.L.; Kremer, H.P.H.; Sinke, R.J.

    2004-01-01

    We report upon a Dutch autosomal dominant cerebellar ataxia (ADCA) family, clinically characterized by a late-onset (>40 years), slowly progressive, isolated spinocerebellar ataxia (SCA). Neuropathological examination in one affected subject showed neuronal loss in the Purkinje cell layer,

  12. Role of high mobility group box 1 (HMGB1 in SCA17 pathogenesis.

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    Li-Ching Lee

    Full Text Available Spinocerebellar ataxia type 17 (SCA17 involves the expression of a polyglutamine (polyQ expanded TATA-binding protein (TBP, a general transcription initiation factor. TBP interacts with other protein factors, including high mobility group box 1 (HMGB1, to regulate gene expression. Previously, our proteomic analysis of soluble proteins prepared from mutant TBP (TBP/Q61 expressing cells revealed a reduced concentration of HMGB1. Here, we show that HMGB1 can be incorporated into mutant TBP aggregates, which leads to reduced soluble HMGB1 levels in TBP/Q(61∼79 expressing cells. HMGB1 overexpression reduced mutant TBP aggregation. HMGB1 cDNA and siRNA co-transfection, as well as an HSPA5 immunoblot and luciferase reporter assay demonstrated the important role of HMGB1 in the regulation of HSPA5 transcription. In starvation-stressed TBP/Q36 and TBP/Q79 cells, increased reactive oxygen species generation accelerated the cytoplasmic translocation of HMGB1, which accompanied autophagy activation. However, TBP/Q79 cells displayed a decrease in autophagy activation as a result of the reduction in the cytoplasmic HMGB1 level. In neuronal SH-SY5Y cells with induced TBP/Q(61∼79 expression, HMGB1 expression was reduced and accompanied by a significant reduction in the total outgrowth and branches in the TBP/Q(61∼79 expressing cells compared with the non-induced cells. The decreased soluble HMGB1 and impaired starvation-induced autophagy in cells suggest that HMGB1 may be a critical modulator of polyQ disease pathology and may represent a target for drug development.

  13. Parkinsonian phenotype in Machado-Joseph disease (MJD/SCA3: a two-case report

    Directory of Open Access Journals (Sweden)

    Vasconcelos João

    2011-10-01

    Full Text Available Abstract Background Machado-Joseph disease (MJD, or spinocerebellar ataxia type 3 (SCA3, is an autosomal dominant neurodegenerative disorder of late onset, which is caused by a CAG repeat expansion in the coding region of the ATXN3 gene. This disease presents clinical heterogeneity, which cannot be completely explained by the size of the repeat tract. MJD presents extrapyramidal motor signs, namely Parkinsonism, more frequently than the other subtypes of autosomal dominant cerebellar ataxias. Although Parkinsonism seems to segregate within MJD families, only a few MJD patients develop parkinsonian features and, therefore, the clinical and genetic aspects of these rare presentations remain poorly investigated. The main goal of this work was to describe two MJD patients displaying the parkinsonian triad (tremor, bradykinesia and rigidity, namely on what concerns genetic variation in Parkinson's disease (PD associated loci (PARK2, LRRK2, PINK1, DJ-1, SNCA, MAPT, APOE, and mtDNA tRNAGln T4336C. Case presentation Patient 1 is a 40 year-old female (onset at 30 years of age, initially with a pure parkinsonian phenotype (similar to the phenotype previously reported for her mother. Patient 2 is a 38 year-old male (onset at 33 years of age, presenting an ataxic phenotype with parkinsonian features (not seen either in other affected siblings or in his father. Both patients presented an expanded ATXN3 allele with 72 CAG repeats. No PD mutations were found in the analyzed loci. However, allelic variants previously associated with PD were observed in DJ-1 and APOE genes, for both patients. Conclusions The present report adds clinical and genetic information on this particular and rare MJD presentation, and raises the hypothesis that DJ-1 and APOE polymorphisms may confer susceptibility to the parkinsonian phenotype in MJD.

  14. Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13).

    Science.gov (United States)

    Figueroa, Karla P; Waters, Michael F; Garibyan, Vartan; Bird, Thomas D; Gomez, Christopher M; Ranum, Laura P W; Minassian, Natali A; Papazian, Diane M; Pulst, Stefan M

    2011-03-29

    Gain-of function or dominant-negative mutations in the voltage-gated potassium channel KCNC3 (Kv3.3) were recently identified as a cause of autosomal dominant spinocerebellar ataxia. Our objective was to describe the frequency of mutations associated with KCNC3 in a large cohort of index patients with sporadic or familial ataxia presenting to three US ataxia clinics at academic medical centers. DNA sequence analysis of the coding region of the KCNC3 gene was performed in 327 index cases with ataxia. Analysis of channel function was performed by expression of DNA variants in Xenopus oocytes. Sequence analysis revealed two non-synonymous substitutions in exon 2 and five intronic changes, which were not predicted to alter splicing. We identified another pedigree with the p.Arg423His mutation in the highly conserved S4 domain of this channel. This family had an early-onset of disease and associated seizures in one individual. The second coding change, p.Gly263Asp, subtly altered biophysical properties of the channel, but was unlikely to be disease-associated as it occurred in an individual with an expansion of the CAG repeat in the CACNA1A calcium channel. Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. The p.Arg423His mutation is recurrent in different populations and associated with early onset. In contrast to previous p.Arg423His mutation carriers, we now observed seizures and mild mental retardation in one individual. This study confirms the wide phenotypic spectrum in SCA13.

  15. Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13.

    Directory of Open Access Journals (Sweden)

    Karla P Figueroa

    2011-03-01

    Full Text Available Gain-of function or dominant-negative mutations in the voltage-gated potassium channel KCNC3 (Kv3.3 were recently identified as a cause of autosomal dominant spinocerebellar ataxia. Our objective was to describe the frequency of mutations associated with KCNC3 in a large cohort of index patients with sporadic or familial ataxia presenting to three US ataxia clinics at academic medical centers.DNA sequence analysis of the coding region of the KCNC3 gene was performed in 327 index cases with ataxia. Analysis of channel function was performed by expression of DNA variants in Xenopus oocytes.Sequence analysis revealed two non-synonymous substitutions in exon 2 and five intronic changes, which were not predicted to alter splicing. We identified another pedigree with the p.Arg423His mutation in the highly conserved S4 domain of this channel. This family had an early-onset of disease and associated seizures in one individual. The second coding change, p.Gly263Asp, subtly altered biophysical properties of the channel, but was unlikely to be disease-associated as it occurred in an individual with an expansion of the CAG repeat in the CACNA1A calcium channel.Mutations in KCNC3 are a rare cause of spinocerebellar ataxia with a frequency of less than 1%. The p.Arg423His mutation is recurrent in different populations and associated with early onset. In contrast to previous p.Arg423His mutation carriers, we now observed seizures and mild mental retardation in one individual. This study confirms the wide phenotypic spectrum in SCA13.

  16. The SCA1 (Spinocerebellar ataxia type 1 and MJD (Machado-Joseph disease CAG repeats in normal individuals: segregation analysis and allele frequencies

    Directory of Open Access Journals (Sweden)

    Wiezel Cláudia Emília Vieira

    2003-01-01

    Full Text Available Spinocerebellar ataxia type 1 (SCA1 and Machado-Joseph disease (MJD/SCA3 are autosomal dominant neurodegenerative diseases caused by expansions of a CAG trinucleotide repeat in the SCA1 and MJD genes. These expanded sequences are unstable upon transmission, leading to an intergeneration increase in the number of repeats (dynamic mutation. The transmission of the CAG repeat was studied in normal mother-father-child trios, referred for paternity testing (SCA1, n = 367; MJD, n = 879. No segregation distortion was detected. The CAG allele frequencies were determined in 330 unrelated individuals (fathers from couples tested for paternity. The allele frequency distributions did not differ from those previously reported for European populations. The estimated values for the statistic parameters indicating diversity at the SCA1 locus did not differ much from those reported previously for other STRs in the Brazilian population, while those for the MJD locus were close to or higher than the maximum values of previous reports. This shows that SCA1 and MJD are highly informative loci for applications in genetic and population studies and for forensic analysis.

  17. Pengaruh Sales Call Anxiety (SCA pada Kinerja Salespersons Asuransi Jiwa dengan Trait Negative Affectivity (Trait-Na

    Directory of Open Access Journals (Sweden)

    Rita Rita

    2012-11-01

    Full Text Available This study empirically examines the effect of sales call anxiety (SCA on salesperson performance, good performance in the form of sales volume and sales interactions. This study tested the hypothesis to identify early factors (antecedents that may affect the sales call anxiety (SCA. Initial factors suspected as the cause of anxiety in sales interactions (SCA are divided into two conditions, namely canvassing and closing condition. Canvassing consisted of meeting new people, customer with high social status, and being assertive, while the closing is a condition consisting of asking for commitment, and discussing performance with sales manager. The population in this study is all life insurance company salesperson in Palangkaraya. In this study, questionnaires were distributed to 200 people a life insurance salesperson, and then used as a sample is a total of 147 respondents who have a tendency to trait-NA. The sampling method used was purposive sampling. The analysis showed that when the salesperson must meet new customers, customers with a high social status, when they should be able to introduce himself and mission well (canvassing, when they should ask for customer commitments after several meetings and interviews with candidates customers, and when the salesperson must discuss the results of their performance with the sales manager (closing, causing anxiety for the salesperson, because when interacting with potential customers, they have a negative perception of the ability of self, negative perceptions of the mind customers in assessing their work when interacting, the emergence of physiological symptoms, and they take action "escape" of the situation, or the so-called protective action.

  18. Assimilation of MODIS Snow Cover Area Data in a Distributed Hydrological Model Using the Particle Filter

    Directory of Open Access Journals (Sweden)

    Milan Kalas

    2013-11-01

    Full Text Available Snow is an important component of the water cycle, and its estimation in hydrological models is of great significance concerning the simulation and forecasting of flood events due to snow-melt. The assimilation of Snow Cover Area (SCA in physical distributed hydrological models is a possible source of improvement of snowmelt-related floods. In this study, the assimilation in the LISFLOOD model of the MODIS sensor SCA has been evaluated, in order to improve the streamflow simulations of the model. This work is realized with the final scope of improving the European Flood Awareness System (EFAS pan-European flood forecasts in the future. For this purpose daily 500 m resolution MODIS satellite SCA data have been used. Tests were performed in the Morava basin, a tributary of the Danube, for three years. The particle filter method has been chosen for assimilating the MODIS SCA data with different frequencies. Synthetic experiments were first performed to validate the assimilation schemes, before assimilating MODIS SCA data. Results of the synthetic experiments could improve modelled SCA and discharges in all cases. The assimilation of MODIS SCA data with the particle filter shows a net improvement of SCA. The Nash of resulting discharge is consequently increased in many cases.

  19. T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse.

    Science.gov (United States)

    Chou, An-Hsun; Chen, Ying-Ling; Chiu, Ching-Chi; Yuan, Shin-Je; Weng, Yi-Hsin; Yeh, Tu-Hsueh; Lin, Yun-Lian; Fang, Jim-Min; Wang, Hung-Li

    2015-12-01

    More studies are required to develop therapeutic agents for treating spinocerebellar ataxia type 3 (SCA3), which is caused by mutant polyglutamine-expanded ataxin-3 and is the most prevalent subtype of spinocerebellar ataxias. T1-11 [N6-(4-Hydroxybenzyl) adenosine], isolated from a Chinese medicinal herb Gastordia elata, is an adenosine A2A receptor agonist. SCA3 and Huntington's disease (HD) belong to a family of polyglutamine neurodegenerative diseases. T1-11 exerted a therapeutic effect on HD transgenic mouse by decreasing protein level of polyglutamine-expanded huntingtin in the striatum. In the present study, we test the possibility that T1-11 or JMF1907 [N6-(3-Indolylethyl) adenosine], a synthetic analog of T1-11, alleviates pontine neuronal death, cerebellar transcriptional downregulation and ataxic symptom in the SCA3 transgenic mouse expressing HA-tagged polyglutamine-expanded ataxin-3-Q79 (ataxin-3-Q79HA). Daily oral administration of T1-11 or JMF1907 prevented neuronal death of pontine nuclei in the SCA3 mouse with a dose-dependent manner. Oral application of T1-11 or JMF1907 reversed mutant ataxin-3-Q79-induced cerebellar transcriptional repression in the SCA3 transgenic mouse. T1-11 or JMF1907 ameliorated the symptom of motor incoordination displayed by SCA3 mouse. Oral administration of T1-11 or JMF1907 significantly decreased protein level of ataxin-3-Q79HA in the pontine nuclei or cerebellum of SCA3 mouse. T1-11 or JMF1907 significantly augmented the chymotrypsin-like activity of proteasome in the pontine nuclei or cerebellum of SCA3 mouse. Our results suggests that T1-11 and JMF1907 alleviate pontine neuronal death, cerebellar transcriptional downregulation and ataxic symptom of SCA3 transgenic mouse by augmenting the proteasome activity and reducing the protein level of polyglutamine-expanded ataxin-3-Q79 in the pontine nuclei and cerebellum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. A novel transgenic rat model for spinocerebellar ataxia type 17 recapitulates neuropathological changes and supplies in vivo imaging biomarkers.

    Science.gov (United States)

    Kelp, Alexandra; Koeppen, Arnulf H; Petrasch-Parwez, Elisabeth; Calaminus, Carsten; Bauer, Claudia; Portal, Esteban; Yu-Taeger, Libo; Pichler, Bernd; Bauer, Peter; Riess, Olaf; Nguyen, Huu Phuc

    2013-05-22

    Spinocerebellar ataxia 17 (SCA17) is an autosomal-dominant, late-onset neurodegenerative disorder caused by an expanded polyglutamine (polyQ) repeat in the TATA-box-binding protein (TBP). To further investigate this devastating disease, we sought to create a first transgenic rat model for SCA17 that carries a full human cDNA fragment of the TBP gene with 64 CAA/CAG repeats (TBPQ64). In line with previous observations in mouse models for SCA17, TBPQ64 rats show a severe neurological phenotype including ataxia, impairment of postural reflexes, and hyperactivity in early stages followed by reduced activity, loss of body weight, and early death. Neuropathologically, the severe phenotype of SCA17 rats was associated with neuronal loss, particularly in the cerebellum. Degeneration of Purkinje, basket, and stellate cells, changes in the morphology of the dendrites, nuclear TBP-positive immunoreactivity, and axonal torpedos were readily found by light and electron microscopy. While some of these changes are well recapitulated in existing mouse models for SCA17, we provide evidence that some crucial characteristics of SCA17 are better mirrored in TBPQ64 rats. Thus, this SCA17 model represents a valuable tool to pursue experimentation and therapeutic approaches that may be difficult or impossible to perform with SCA17 transgenic mice. We show for the first time positron emission tomography (PET) and diffusion tensor imaging (DTI) data of a SCA animal model that replicate recent PET studies in human SCA17 patients. Our results also confirm that DTI are potentially useful correlates of neuropathological changes in TBPQ64 rats and raise hope that DTI imaging could provide a biomarker for SCA17 patients.

  1. Isospin diffusion in binary collisions of 32S+Ca,4840 and 32S+48Ti at 17.7 MeV/nucleon

    Science.gov (United States)

    Piantelli, S.; Valdré, S.; Barlini, S.; Casini, G.; Colonna, M.; Baiocco, G.; Bini, M.; Bruno, M.; Camaiani, A.; Carboni, S.; Cicerchia, M.; Cinausero, M.; D'Agostino, M.; Degerlier, M.; Fabris, D.; Gelli, N.; Gramegna, F.; Gruyer, D.; Kravchuk, V. L.; Mabiala, J.; Marchi, T.; Morelli, L.; Olmi, A.; Ottanelli, P.; Pasquali, G.; Pastore, G.

    2017-09-01

    The systems 32S+Ca,4840 and 32S+48Ti at 17.7 MeV/nucleon were investigated with the setup general array for fragment identification and for emitted light particles in dissipative collisions (GARFIELD) plus ring counter (RCo) at Laboratori Nazionali di Legnaro (LNL) of Istituto Nazionale di Fisica Nucleare (INFN). Fusion evaporation (FE), fusion fission (FF), and deep inelastic (DIC) events were identified, also through the comparison with the prediction of a transport model (stochastic mean field, SMF), coupled to GEMINI++ as an afterburner. This work mainly deals with the study of isospin transport phenomena in DIC events. In particular, the isospin diffusion is highlighted by comparing the average isotopic content of the quasiprojectile (QP) remnants observed when the target is the N =Z nucleus 40Ca and when it is the neutron-rich 48Ca. Also, the d /p and t /p ratios for particles forward emitted with respect to the QP were found to increase with increasing N /Z of the target.

  2. SCA1+ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions

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    Bastiaan C. Du Pré

    2017-09-01

    Full Text Available Stem cell antigen 1-positive (SCA1+ cells (SPCs have been investigated in cell-based cardiac repair and pharmacological research, although improved cardiac function after injection has been variable and the mode of action remains unclear. Circadian (24-hr rhythms are biorhythms regulated by molecular clocks that play an important role in (pathophysiology. Here, we describe (1 the presence of a molecular circadian clock in SPCs and (2 circadian rhythmicity in SPC function. We isolated SPCs from human fetal heart and found that these cells possess a molecular clock based on typical oscillations in core clock components BMAL1 and CRY1. Functional analyses revealed that circadian rhythmicity also governs SPC proliferation, stress tolerance, and growth factor release, with large differences between peaks and troughs. We conclude that SPCs contain a circadian molecular clock that controls crucial cellular functions. Taking circadian rhythms into account may improve reproducibility and outcome of research and therapies using SPCs.

  3. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3

    NARCIS (Netherlands)

    Verbeek, D S; van de Warrenburg, B P; Wesseling, P; Pearson, P L; Kremer, H P; Sinke, R J

    2004-01-01

    We report upon a Dutch autosomal dominant cerebellar ataxia (ADCA) family, clinically characterized by a late-onset (>40 years), slowly progressive, isolated spinocerebellar ataxia (SCA). Neuropathological examination in one affected subject showed neuronal loss in the Purkinje cell layer, dentate

  4. Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [{sup 123}I]{beta}-CIT SPECT analysis

    Energy Technology Data Exchange (ETDEWEB)

    Scherfler, Christoph; Boesch, Sylvia M.; Seppi, Klaus; Wenning, Gregor K.; Poewe, Werner [Innsbruck Medical University, Department of Neurology, Innsbruck (Austria); Donnemiller, Eveline; Virgolini, Irene [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Weirich-Schwaiger, Helga [Innsbruck Medical University, Department of Biology and Human Genetics, Innsbruck (Austria); Goebel, Georg [Innsbruck Medical University, Department of Medical Statistics, Informatics and Health Economics, Innsbruck (Austria)

    2006-09-15

    The purpose of this study was to investigate the monoamine transporter status of dopamine, serotonin and norepinephrine throughout the brain in spinocerebellar ataxia type 2 (SCA2). To this end, nine patients were studied with [{sup 123}I]{beta}-CIT SPECT. Data were compared with ten age-matched healthy control subjects and ten patients with young-onset Parkinson's disease (YOPD), matched for age. Parametric SPECT images of the specific-to-non-displaceable equilibrium partition coefficient (V{sub 3}{sup ''}), which is proportional to the receptor density (B{sub max}), were generated. In order to objectively localise focal changes in {beta}-CIT uptake throughout the brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to SPECT images. Data clusters revealed by SPM, showing significant differences in V{sub 3}{sup ''} values between groups, were transformed onto the individual V{sub 3}{sup ''} image to obtain mean regional uptake values. Both SCA2 and YOPD patients showed significant decreases in striatal [{sup 123}I]{beta}-CIT SPECT uptake when compared with controls. However, in SCA2 patients, additional reductions in caudate/anterior putamen, midbrain and pons [{sup 123}I]{beta}-CIT uptake were localised with SPM. Voxel-wise analysis of [{sup 123}I]{beta}-CIT SPECT revealed more widespread decline of monoamine transporter availability in SCA2 than in YOPD, reflecting differences in the underlying pathology. We suggest that the quantification of midbrain and pons [{sup 123}I]{beta}-CIT signal is likely to improve the diagnostic accuracy in patients presenting with clinical features of both SCA2 and YOPD at initial investigation. (orig.)

  5. Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation

    OpenAIRE

    Zuehlke, Christine; Edener, Ulf; Woellner, Janine; Hehr, Ute; Kohl, Zacharias; Schilling, Stefan; Kreuz, Friedmar; Bauer, Peter; Bernard, Veronica; Gillessen-Kaesbach, Gabriele

    2010-01-01

    Abstract The autosomal dominantly inherited spinocerebellar ataxias are a heterogeneous group of neurodegenerative disorders primarily affecting the cerebellum. Genetically, 26 different loci have been identified so far whereas the corresponding gene has not yet been determined for 10 of them. Recently, mutations in the ATPase family gene 3-like 2 gene were presented to cause spinocerebellar ataxia type 28. In order to define the frequency of SCA28 mutations, we performed molecular...

  6. MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Caixia [Department of Surgery, University of North Carolina at Chapel Hill (United States); Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004 (China); Samuelson, Lisa; Cui, Cai-Bin; Sun, Yangzhong [Department of Surgery, University of North Carolina at Chapel Hill (United States); Gerber, David A., E-mail: david_gerber@med.unc.edu [Department of Surgery, University of North Carolina at Chapel Hill (United States); Lineberger Cancer Center, University of North Carolina at Chapel Hill (United States)

    2011-06-17

    Highlights: {yields} Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1{sup +} HPC proliferation and colony formation. {yields} Activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. {yields} Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs' self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1{sup +} HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1{sup +} HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation.

  7. Spinocerebellar ataxia type 17: Report of a family with reduced penetrance of an unstable Gln49 TBP allele, haplotype analysis supporting a founder effect for unstable alleles and comparative analysis of SCA17 genotypes

    Directory of Open Access Journals (Sweden)

    Schwinger Eberhard

    2005-07-01

    Full Text Available Abstract Background Spinocerebellar ataxia type 17 (SCA17, a neurodegenerative disorder in man, is caused by an expanded polymorphic polyglutamine-encoding trinucleotide repeat in the gene for TATA-box binding protein (TBP, a main transcription factor. Observed pathogenic expansions ranged from 43 – 63 glutamine (Gln codons (Gln43–63. Reduced penetrance is known for Gln43–48 alleles. In the vast majority of families with SCA17 an expanded CAG repeat interrupted by a CAA CAG CAA element is inherited stably. Results Here, we report the first pedigree with a Gln49 allele that is a not interrupted, b unstable upon transmission, and c associated with reduced penetrance or very late age of onset. The 76-year-old father of two SCA17 patients carries the Gln49 TBP allele but presents without obvious neurological symptoms. His children with Gln53 and Gln52 developed ataxia at the age of 41 and 50. Haplotype analysis of this and a second family both with uninterrupted expanded and unstable pathological SCA17 alleles revealed a common core genotype not present in the interrupted expansion of an unrelated SCA17 patient. Review of the literature did not present instability in SCA17 families with expanded alleles interrupted by the CAA CAG CAA element. Conclusion The presence of a Gln49 SCA17 allele in an asymptomatic 76-year-old male reams the discussion of reduced penetrance and genotypes producing very late disease onset. In SCA17, uninterrupted expanded alleles of TBP are associated with repeat instability and a common founder haplotype. This suggests for uninterrupted expanded alleles a mutation mechanism and some clinical genetic features distinct from those alleles interrupted by a CAA CAG CAA element.

  8. An efficient method for applying a differential equation to deriving the spatial distribution of specific catchment area from gridded digital elevation models

    Science.gov (United States)

    Qin, Cheng-Zhi; Ai, Bei-Bei; Zhu, A.-Xing; Liu, Jun-Zhi

    2017-03-01

    Deriving the spatial distribution of specific catchment area (SCA) from a gridded digital elevation model (DEM) is one of the most important issues in digital terrain analysis. Conventional methods usually estimate SCA for each cell using a flow direction algorithm, but the results obtained are often unsatisfactory. Recently, Gallant and Hutchinson (2011, Water Resources Research, 47(5), W05535) proposed a differential equation which quantifies the change of SCA along a slope line, and thus the numerical solution of SCA at any point on a surface can be calculated accurately by integrating the differential equation. However, obtaining the numerical SCA solution based on this differential equation is so computationally intensive that it is too time-consuming to use it to derive the overall SCA spatial distribution from a gridded DEM. In this study, we developed a parallel algorithm based on OpenMP to make the numerical SCA solution based on Gallant and Hutchinson (2011)'s differential equation practical to derive the spatial distribution of SCA from a gridded DEM. Experiments based on two artificial surfaces with theoretical SCA and a more complex real terrain surface demonstrated that the proposed parallel algorithm obtained satisfactory acceleration performance and a much lower error than the MFD-md algorithm, which is a representative of conventional grid-based flow direction algorithms. Due to the speedup effects of the proposed parallel algorithm, we analyzed the effects of the DEM grid size and integration step length on the numerical SCA solution in detailed experiments. The experimental results suggested that the proposed algorithm performed best normally at the resolution of 5 m. A step ratio of 0.5 is suitable in applications of the proposed parallel algorithm.

  9. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters.

    Science.gov (United States)

    Smeriglio, Piera; Alonso-Martin, Sonia; Masciarelli, Silvia; Madaro, Luca; Iosue, Ilaria; Marrocco, Valeria; Relaix, Frédéric; Fazi, Francesco; Marazzi, Giovanna; Sassoon, David A; Bouché, Marina

    2016-04-01

    Understanding the regulation of the stem cell fate is fundamental for designing novel regenerative medicine strategies. Previous studies have suggested that pharmacological treatments with small molecules provide a robust and reversible regulation of the stem cell program. Previously, we showed that treatment with a vanadium compound influences muscle cell fatein vitro In this study, we demonstrate that treatment with the phosphotyrosine phosphatase inhibitor bisperoxovanadium (BpV) drives primary muscle cells to a poised stem cell stage, with enhanced function in muscle regenerationin vivofollowing transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self-renewal potentialin vivoand replenished the niche in both satellite and interstitial cell compartments. Moreover, we found that BpV treatment induces specific activating chromatin modifications at the promoter regions of genes associated with stem cell fate, includingSca-1andPw1 Thus, our findings indicate that BpV resets the cell fate program by specific epigenetic regulations, such that the committed myogenic cell fate is redirected to an earlier progenitor cell fate stage, which leads to an enhanced regenerative stem cell potential.-Smeriglio, P., Alonso-Martin, S., Masciarelli, S., Madaro, L., Iosue, I., Marrocco, V., Relaix, F., Fazi, F., Marazzi, G., Sassoon, D. A., Bouché, M. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functionsviaepigenetic modulation of Sca-1 and Pw1 promoters. © FASEB.

  10. Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice.

    Science.gov (United States)

    Riley, Sean P; Cardwell, Marissa M; Chan, Yvonne G Y; Pruneau, Ludovic; Del Piero, Fabio; Martinez, Juan J

    2015-12-01

    Spotted fever group (SFG) rickettsial species are obligate intracellular tick-borne pathogens that are responsible for important human diseases. Previous reports have demonstrated the feasibility of using recombinant surface cell antigen Sca5/OmpB to elicit protective immunity against homologous challenges using murine models of Mediterranean spotted fever and Rocky Mountain spotted fever. In addition, the feasibility of generating cross-protective immunity against related rickettsial species has also been established, but the molecular basis for these phenomena was not explored. Here, we demonstrate that vaccination of C3H/HeN mice with a recombinant OmpB domain derived from Rickettsia conorii induced high titer humoral immune responses that are capable of recognizing the native OmpB protein at the R. rickettsii outer membrane, but this immunization was not sufficient to induce effective protective immunity. In contrast, animals vaccinated with a corresponding OmpB domain derived from R. rickettsii protected animals from fatal outcomes. These results demonstrate that vaccination with nearly identical antigens may not be an effective strategy to induce wide-ranging protective immunity against related SFG Rickettsia species. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of {approximately} 3 cM on chromosome 14q24.3-q32.2

    Energy Technology Data Exchange (ETDEWEB)

    Stevanin, G.; Cancel, G.; Duerr, A.; Dubourg, O.; Agid, Y.; Brice, A. [Hopital de la Salpetriere, Paris (France); Chneiweiss, H.; Weissenbach, J.; Cann, H.M.

    1995-01-01

    SCA3, the gene for spinal cerebellar ataxia 3, was recently mapped to a 15-cM interval between D14S67 and D14S81 on chromosome 14q, by linkage analysis in two families of French ancestry. The SCA3 candidate region has now been refined by linkage analysis with four new microsatellite markers (D14S256, D14S291, D14S280, and AFM343vf1) in the same two families, in which 19 additional individuals were genotyped, and in a third French family. Combined two-point linkage analyses show that the new markers, D14S280 and AFM343vf1, are tightly linked to the SCA3 locus, with maximal lod scores, at recombination fraction, ({theta}) = .00, of 7.05 and 13.70, respectively. Combined multipoint and recombinant haplotype analyses localize the SCA3 locus to a 3-cM interval flanked by D14S291 and D14S81. The same allele for D14S280 segregates with the disease locus in the three kindreds. This allele is frequent in the French population, however, and linkage disequilibrium is not clearly established. The SCA3 locus remains within the 29-cM region on 14q24.3-q32.2 containing the gene for the Machado-Joseph disease, which is clinically related to the phenotype determined by SCA3, but it cannot yet be concluded that both diseases result from alterations of the same gene. 30 refs., 3 figs., 3 tabs.

  12. Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    Full Text Available Insulin-like growth factor 1 (IGF-1 and hepatocyte growth factor (HGF are two potent cell survival and regenerative factors in response to myocardial injury (MI. We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01. IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01 and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

  13. Changes in the number of CD31-CD45-Sca-1+ cells and Shh signaling pathway involvement in the lungs of mice with emphysema and relevant effects of acute adenovirus infection.

    Science.gov (United States)

    Deng, Minhua; Li, Jinhua; Gan, Ye; Chen, Yan; Chen, Ping

    2017-01-01

    COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31-CD45-Sca-1+ cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI). BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31-CD45-Sca-1+ cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured. CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31-CD45-Sca-1+ cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31-CD45-Sca-1+ cells and activated the suppression of the Shh signaling pathway. Both CD31-CD45-Sca-1+ cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31-CD45-Sca-1+ cells and Shh signaling pathway molecules were upregulated during AAI, indicating that they play a protective role in the epithelial repair process after AAI injury.

  14. Decadal trends in the seasonal-cycle amplitude of terrestrial CO2 exchange resulting from the ensemble of terrestrial biosphere models

    Directory of Open Access Journals (Sweden)

    Akihiko Ito

    2016-05-01

    Full Text Available The seasonal-cycle amplitude (SCA of the atmosphere–ecosystem carbon dioxide (CO2 exchange rate is a useful metric of the responsiveness of the terrestrial biosphere to environmental variations. It is unclear, however, what underlying mechanisms are responsible for the observed increasing trend of SCA in atmospheric CO2 concentration. Using output data from the Multi-scale Terrestrial Model Intercomparison Project (MsTMIP, we investigated how well the SCA of atmosphere–ecosystem CO2 exchange was simulated with 15 contemporary terrestrial ecosystem models during the period 1901–2010. Also, we made attempt to evaluate the contributions of potential mechanisms such as atmospheric CO2, climate, land-use, and nitrogen deposition, through factorial experiments using different combinations of forcing data. Under contemporary conditions, the simulated global-scale SCA of the cumulative net ecosystem carbon flux of most models was comparable in magnitude with the SCA of atmospheric CO2 concentrations. Results from factorial simulation experiments showed that elevated atmospheric CO2 exerted a strong influence on the seasonality amplification. When the model considered not only climate change but also land-use and atmospheric CO2 changes, the majority of the models showed amplification trends of the SCAs of photosynthesis, respiration, and net ecosystem production (+0.19 % to +0.50 % yr−1. In the case of land-use change, it was difficult to separate the contribution of agricultural management to SCA because of inadequacies in both the data and models. The simulated amplification of SCA was approximately consistent with the observational evidence of the SCA in atmospheric CO2 concentrations. Large inter-model differences remained, however, in the simulated global tendencies and spatial patterns of CO2 exchanges. Further studies are required to identify a consistent explanation for the simulated and observed amplification trends, including their

  15. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Directory of Open Access Journals (Sweden)

    Swati Khare

    Full Text Available The autosomal dominant spinocerebellar ataxias (SCAs are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3. We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR. Together, these results indicate that the neurodevelopmental

  16. Inversion and space-time-averaging algorithms for ScaRaB (Scanner for the Earth Radiation Budget. Comparison with ERBE

    Directory of Open Access Journals (Sweden)

    M. Viollier

    Full Text Available Establishment of a uniform long-term record of "top-of-the atmosphere" (TOA Earth radiation budget (ERB components, on a scale appropriate to the study of cloud radiation interactions, requires that the data obtained from different observation missions satisfy two basic conditions: (1 the broadband shortwave (SW:0.2–4 µm and longwave (LW: 4–50 µm radiances must be demonstrably made on the same absolute scale; and (2 the methods used first to convert the instantaneous (filtered radiances into (unfiltered SW and LW radiant fluxes, and then to perform the space-time integrations to yield regional monthly means, must be consistent. Here we consider mainly the second point, with regard to the ScaRaB/Meteor mission in orbit since 25 January 1994 and observing the Earth since 24 February 1994. The objective of this mission is to determine the TOA ERB components and so to provide a continuation of the NASA ERBE scanner mission (November 1984–February 1990. We show how results compatible with ERBE can be obtained by taking into account the instrumental characteristics and the satellite orbit parameters: spectral response of the broadband channels, Earth local time of observation. Considering the spectral response of the ScaRaB broadband channels, we show that no spectral correction is required in the longwave domain, whereas a correction of +4.5% must be applied in the shortwave domain for clear and partly cloudy ocean, in order to compensate for underestimation at the shortest wavelengths. Despite possible differences between ERBE and ScaRaB procedures in values assumed for certain parameters of the scene/cloud identifications, application of these procedures to the same set of ERBE data (spectrally corrected, i.e. "unfiltered" radiances shows that scene identification agreement is close to 90% and that, where there is disagreement, resulting differences in LW fluxes are negligible, those in SW fluxes small. We show that regional and global mean

  17. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Science.gov (United States)

    Khare, Swati; Nick, Jerelyn A; Zhang, Yalan; Galeano, Kira; Butler, Brittany; Khoshbouei, Habibeh; Rayaprolu, Sruti; Hathorn, Tyisha; Ranum, Laura P W; Smithson, Lisa; Golde, Todd E; Paucar, Martin; Morse, Richard; Raff, Michael; Simon, Julie; Nordenskjöld, Magnus; Wirdefeldt, Karin; Rincon-Limas, Diego E; Lewis, Jada; Kaczmarek, Leonard K; Fernandez-Funez, Pedro; Nick, Harry S; Waters, Michael F

    2017-01-01

    The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of

  18. A cellular automata model of Ebola virus dynamics

    Science.gov (United States)

    Burkhead, Emily; Hawkins, Jane

    2015-11-01

    We construct a stochastic cellular automaton (SCA) model for the spread of the Ebola virus (EBOV). We make substantial modifications to an existing SCA model used for HIV, introduced by others and studied by the authors. We give a rigorous analysis of the similarities between models due to the spread of virus and the typical immune response to it, and the differences which reflect the drastically different timing of the course of EBOV. We demonstrate output from the model and compare it with clinical data.

  19. Changes in the number of CD31−CD45−Sca-1+ cells and Shh signaling pathway involvement in the lungs of mice with emphysema and relevant effects of acute adenovirus infection

    Directory of Open Access Journals (Sweden)

    Deng MH

    2017-03-01

    Full Text Available Minhua Deng,1,2 Jinhua Li,2 Ye Gan,3 Yan Chen,2 Ping Chen2 1Respiratory Medicine Department, PLA Rocket Force General Hospital, Beijing, 2Respiratory Medicine Department, 3Rehabilitation Department, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China Background: COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31-CD45-Sca-1+ cells and sonic hedgehog (Shh signaling pathway expression levels in cigarette smoke extract (CSE-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI. Materials and methods: BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31-CD45-Sca-1+ cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured. Results: CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31-CD45-Sca-1+ cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31-CD45-Sca-1+ cells and activated the suppression of the Shh signaling pathway. Conclusion: Both CD31-CD45-Sca-1+ cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31-CD45-Sca-1+ cells and Shh signaling pathway molecules were upregulated

  20. Transient cerebellar alterations during development prior to obvious motor phenotype in a mouse model of spinocerebellar ataxia type 6.

    Science.gov (United States)

    Jayabal, Sriram; Ljungberg, Lovisa; Watt, Alanna J

    2017-02-01

    Spinocerebellar ataxia type 6 (SCA6) is a midlife-onset neurodegenerative disease caused by a CACNA1A mutation; CACNA1A is also implicated in cerebellar development. We have previously shown that when disease symptoms are present in midlife in SCA684Q/84Q mice, cerebellar Purkinje cells spike with reduced rate and precision. In contrast, we find that during postnatal development (P10-13), SCA684Q/84Q Purkinje cells spike with elevated rate and precision. Although surplus climbing fibres are linked to ataxia in other mouse models, we found surplus climbing fibre inputs on developing (P10-13) SCA684Q/84Q Purkinje cells when motor deficits were not detected. Developmental alterations were transient and were no longer observed in weanling (P21-24) SCA684Q/84Q Purkinje cells. Our results suggest that changes in the developing cerebellar circuit can occur without detectable motor abnormalities, and that changes in cerebellar development may not necessarily persist into adulthood. Although some neurodegenerative diseases are caused by mutations in genes that are known to regulate neuronal development, surprisingly, patients may not present disease symptoms until adulthood. Spinocerebellar ataxia type 6 (SCA6) is one such midlife-onset disorder in which the mutated gene, CACNA1A, is implicated in cerebellar development. We wondered whether changes were observed in the developing cerebellum in SCA6 prior to the detection of motor deficits. To address this question, we used a transgenic mouse with a hyper-expanded triplet repeat (SCA684Q/84Q ) that displays late-onset motor deficits at 7 months, and measured cerebellar Purkinje cell synaptic and intrinsic properties during postnatal development. We found that firing rate and precision were enhanced during postnatal development in P10-13 SCA684Q/84Q Purkinje cells, and observed surplus multiple climbing fibre innervation without changes in inhibitory input or dendritic structure during development. Although excess multiple

  1. Toward cloning of a novel ataxia gene: Refined assignment and physical map of the IOSCA locus (SCA8) on 10q24

    Energy Technology Data Exchange (ETDEWEB)

    Nikali, K.; Isosomppi, J.; Suomalainen, A. [Univ. of Helsinki (Finland)] [and others

    1997-01-15

    Infantile onset spinocerebellar ataxia (IOSCA) is a progressive neurological disorder of unknown etiology. It is inherited as an autosomal recessive trait and has so far been reported in just 19 Finnish patients in 13 separate families. We have previously assigned the IOSCA locus (HGMW-approved symbol SCA8) to chromosome 10q, where no previously identified ataxia loci are located. Haplotype analysis combined with genealogical data provided evidence that all the IOSCA cases in Finland originate from a single 30- to 40-generation-old founder mutation. By analyzing extended disease haplotypes observed today, the IOSCA locus can now be restricted to a region between two adjacent microsatellites, D10S192 and D10S1265, with no genetic intermarker distance. We have constructed a detailed physical map of this 270-kb IOSCA region and cytogenetically localized it to 10q24. We have also assigned two previously known genes, PAX2 and CYP17, more precisely into this region, but the sequence analysis of coding regions of these two genes has not revealed mutations in an IOSCA patient. The obtained long-range clones will form the basis for the isolation of a novel ataxia gene. 42 refs., 3 figs.

  2. Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3.

    Directory of Open Access Journals (Sweden)

    Carmen Rodríguez-Cueto

    Full Text Available Spinocerebellar ataxia type-3 (SCA-3 is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia, we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem. These data open the way to search for drugs that might correct these changes.

  3. The Truncated C-terminal Fragment of Mutant ATXN3 Disrupts Mitochondria Dynamics in Spinocerebellar Ataxia Type 3 Models

    Directory of Open Access Journals (Sweden)

    Jung-Yu Hsu

    2017-06-01

    Full Text Available Spinocerebellar ataxia type 3 (SCA3, known as Machado-Joseph disease, is an autosomal dominant disease caused by an abnormal expansion of polyglutamine in ATXN3 gene, leading to neurodegeneration in SCA3 patients. Similar to other neurodegenerative diseases, the dysfunction of mitochondria is observed to cause neuronal death in SCA3 patients. Based on previous studies, proteolytic cleavage of mutant ATXN3 is found to produce truncated C-terminal fragments in SCA3 models. However, whether these truncated mutant fragments disturb mitochondrial functions and result in pathological death is still unclear. Here, we used neuroblastoma cell and transgenic mouse models to examine the effects of truncated mutant ATXN3 on mitochondria functions. In different models, we observed truncated mutant ATXN3 accelerated the formation of aggregates, which translocated into the nucleus to form intranuclear aggregates. In addition, truncated mutant ATXN3 caused more mitochondrial fission, and decreased the expression of mitochondrial fusion markers, including Mfn-1 and Mfn-2. Furthermore, truncated mutant ATXN3 decreased the mitochondrial membrane potential, increased reactive oxygen species and finally increased cell death rate. In transgenic mouse models, truncated mutant ATXN3 also led to more mitochondrial dysfunction, neurodegeneration and cell death in the cerebellums. This study supports the toxic fragment hypothesis in SCA3, and also provides evidence that truncated mutant ATXN3 is severer than full-length mutant one in vitro and in vivo.

  4. Initial observations of fine plasma structures at the flank magnetopause with the complex plasma analyzer SCA-1 onboard the Interball Tail Probe

    Directory of Open Access Journals (Sweden)

    O. L. Vaisberg

    Full Text Available The fast plasma analyzer EU-1 of the SCA-1 complex plasma spectrometer is installed onboard the Interball Tail Probe (Interball-1. It provides fast three-dimensional measurements of the ion distribution function on the low-spin-rate Prognoz satellite (about 2min. The EU-1 ion spectrometer with virtual aperture consists of two detectors with 16 E/Q narrow-angle analyzers and electrostatic scanners. This configuration allows one to measure the ion distribution function in three dimensions (over 15 energy steps in 50 eV/Q–5.0 keV/Q energy range in 64 directions in 7.5 s, which makes it independent of the slow rotation speed of the satellite. A description of the instrument and its capabilities is given. We present here the preliminary results of measurements of ions for two cases of the dawn low- and mid-latitude magnetopause crossings. The properties of observed ion structures and their tentative explanation are presented. The 12 September 1995 pass at low latitude at about 90° solar-zenith angle on the dawn side of the magnetosphere is considered in more detail. Dispersive ions are seen at the edge of the magnetopause and at the edges of subsequently observed plasma structures. Changes in ion velocity distribution in plasma structures observed after the first magnetopause crossing suggest that what resembles multiple magnetopause crossings may be plasma blobs penetrating the magnetosphere. Observed variations of plasma parameters near magnetopause structures suggest nonstationary reconnection as the most probable mechanism for observed structures.

  5. Initial observations of fine plasma structures at the flank magnetopause with the complex plasma analyzer SCA-1 onboard the Interball Tail Probe

    Directory of Open Access Journals (Sweden)

    O. L. Vaisberg

    1997-05-01

    Full Text Available The fast plasma analyzer EU-1 of the SCA-1 complex plasma spectrometer is installed onboard the Interball Tail Probe (Interball-1. It provides fast three-dimensional measurements of the ion distribution function on the low-spin-rate Prognoz satellite (about 2min. The EU-1 ion spectrometer with virtual aperture consists of two detectors with 16 E/Q narrow-angle analyzers and electrostatic scanners. This configuration allows one to measure the ion distribution function in three dimensions (over 15 energy steps in 50 eV/Q–5.0 keV/Q energy range in 64 directions in 7.5 s, which makes it independent of the slow rotation speed of the satellite. A description of the instrument and its capabilities is given. We present here the preliminary results of measurements of ions for two cases of the dawn low- and mid-latitude magnetopause crossings. The properties of observed ion structures and their tentative explanation are presented. The 12 September 1995 pass at low latitude at about 90° solar-zenith angle on the dawn side of the magnetosphere is considered in more detail. Dispersive ions are seen at the edge of the magnetopause and at the edges of subsequently observed plasma structures. Changes in ion velocity distribution in plasma structures observed after the first magnetopause crossing suggest that what resembles multiple magnetopause crossings may be plasma blobs penetrating the magnetosphere. Observed variations of plasma parameters near magnetopause structures suggest nonstationary reconnection as the most probable mechanism for observed structures.

  6. Progressive impairment of cerebellar mGluR signalling and its therapeutic potential for cerebellar ataxia in spinocerebellar ataxia type 1 model mice.

    Science.gov (United States)

    Shuvaev, Anton N; Hosoi, Nobutake; Sato, Yamato; Yanagihara, Dai; Hirai, Hirokazu

    2017-01-01

    Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by a gene defect, leading to movement disorder such as cerebellar ataxia. It remains largely unknown which functional defect contributes to the cerebellar ataxic phenotype in SCA1. In this study, we report progressive dysfunction of metabotropic glutamate receptor (mGluR) signalling, which leads to smaller slow synaptic responses, reduced dendritic Ca2+ signals and impaired synaptic plasticity at cerebellar synapses, in the early disease stage of SCA1 model mice. We also show that enhancement of mGluR signalling by a clinically available drug, baclofen, leads to improvement of motor performance in SCA1 mice. SCA1 is an incurable disease with no effective treatment, and our results may provide mechanistic grounds for targeting mGluRs and a novel drug therapy with baclofen to treat SCA1 patients in the future. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease that presents with cerebellar ataxia and motor learning defects. Previous studies have indicated that the pathology of SCA1, as well as other ataxic diseases, is related to signalling pathways mediated by the metabotropic glutamate receptor type 1 (mGluR1), which is indispensable for proper motor coordination and learning. However, the functional contribution of mGluR signalling to SCA1 pathology is unclear. In the present study, we show that SCA1 model mice develop a functional impairment of mGluR signalling which mediates slow synaptic responses, dendritic Ca2+ signals, and short- and long-term synaptic plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses in a progressive manner from the early disease stage (5 postnatal weeks) prior to PC death. Notably, impairment of mGluR-mediated dendritic Ca2+ signals linearly correlated with a reduction of PC capacitance (cell surface area) in disease progression. Enhancement of mGluR signalling by baclofen, a clinically available GABAB receptor

  7. Non-robust numerical implementations impact global carbon and water cycle simulations: a demonstration with two ESM land models

    Science.gov (United States)

    Tang, J.; Riley, W. J.

    2016-12-01

    Numerically robust land modeling is essential for making good predictions of climate change, yet sufficient attention is still due to the quality of numerical methods in land modules of Earth System Models (ESMs). Using CLM (Community Land Model) and ALM (ACME land model), we show through examples that the " popular" sequential coupling approach (SCA) can lead to large predictive errors due to numerically generated pseudo physics. The first example is about the coupling between water movement in roots and soil for simulating the hydraulic root redistribution in CLM. The SCA obtained better simulation of evapotranspiration (ET) at the Blodget Forest site in California as compared to that from the tight coupling approach (TCA) and the two performed equally well for simulating ET at the Tapajos Forest site in Amazon. This result may mislead one to assert that the SCA should be preferred for calibration and prediction. However, SCA led to extreme time step size sensitivity, whereas TCA did not. In global simulations, SCA overestimated ET by as much as 3.5 mm d-1 in some tropical sites, suggesting large land-atmosphere feedbacks could be triggered due to numerical error. The second example focused on the coupling between carbon and nitrogen dynamics in ALM. SCA assumed that the newly mineralized nitrogen is not available for plant and microbe uptake until the next numerical time step. In both site and global simulations, SCA resulted in larger nitrification rates and ecosystem nitrogen losses as compared to those from TCA that tightly couples nitrogen mineralizers and immobilizers. In particular, for long-term simulations driven by the RCP8.5 atmospheric CO2 trajectory, SCA overestimated (compared to the tight coupling approach) global land-atmosphere CO2 exchange by as much as 440 ppmv CO2 equivalent over 300 years. Further considering uncertainty in initial conditions led to a difference as large as 890 ppmv CO2 equivalent. These differences are as large as that

  8. Improvement of distributed snowmelt energy balance modeling with MODIS-based NDSI-derived fractional snow-covered area data

    Science.gov (United States)

    Joel W. Homan; Charles H. Luce; James P. McNamara; Nancy F. Glenn

    2011-01-01

    Describing the spatial variability of heterogeneous snowpacks at a watershed or mountain-front scale is important for improvements in large-scale snowmelt modelling. Snowmelt depletion curves, which relate fractional decreases in snowcovered area (SCA) against normalized decreases in snow water equivalent (SWE), are a common approach to scale-up snowmelt models....

  9. Evaluating MODIS snow products for modelling snowmelt runoff: Case study of the Rio Grande headwaters

    Science.gov (United States)

    Steele, Caitriana; Dialesandro, John; James, Darren; Elias, Emile; Rango, Albert; Bleiweiss, Max

    2017-12-01

    Snow-covered area (SCA) is a key variable in the Snowmelt-Runoff Model (SRM) and in other models for simulating discharge from snowmelt. Landsat Thematic Mapper (TM), Enhanced Thematic Mapper (ETM +) or Operational Land Imager (OLI) provide remotely sensed data at an appropriate spatial resolution for mapping SCA in small headwater basins, but the temporal resolution of the data is low and may not always provide sufficient cloud-free dates. The coarser spatial resolution Moderate Resolution Imaging Spectroradiometer (MODIS) offers better temporal resolution and in cloudy years, MODIS data offer the best alternative for mapping snow cover when finer spatial resolution data are unavailable. However, MODIS' coarse spatial resolution (500 m) can obscure fine spatial patterning in snow cover and some MODIS products are not sensitive to end-of-season snow cover. In this study, we aimed to test MODIS snow products for use in simulating snowmelt runoff from smaller headwater basins by a) comparing maps of TM and MODIS-based SCA and b) determining how SRM streamflow simulations are changed by the different estimates of seasonal snow depletion. We compared gridded MODIS snow products (Collection 5 MOD10A1 fractional and binary SCA; SCA derived from Collection 6 MOD10A1 Normalised Difference Snow Index (NDSI) Snow Cover), and the MODIS Snow Covered-Area and Grain size retrieval (MODSCAG) canopy-corrected fractional SCA (SCAMG), with reference SCA maps (SCAREF) generated from binary classification of TM imagery. SCAMG showed strong agreement with SCAREF; excluding true negatives (where both methods agreed no snow was present) the median percent difference between SCAREF and SCAMG ranged between -2.4% and 4.7%. We simulated runoff for each of the four study years using SRM populated with and calibrated for snow depletion curves derived from SCAREF. We then substituted in each of the MODIS-derived depletion curves. With efficiency coefficients ranging between 0.73 and 0.93, SRM

  10. Raf V Sweatman (162/2014 [2015] ZASCA 22 (20 March 2015 A Simple Illustration of the SCA'S Statutory Misinterpretation of Section 17(4(C of the Road Accident Fund Act 56 of 1998

    Directory of Open Access Journals (Sweden)

    Sarah Fick

    2015-12-01

    Full Text Available In Road Accident Fund v Sweatman (162/2014 [2015] ZASCA 22 (20 March 2015 (hereafter Sweatman the Supreme Court of Appeal was faced with the interpretation of section 17(4(c of the Road Accident Fund Act 56 of 1998 (the "cap provision". The purpose of this note is to assess the court's interpretation of the "cap provision" to determine whether this interpretation is sound. This is achieved by explaining the purpose of the Road Accident Fund and the Amendment Act. Thereafter the general method of calculating loss of income is explored, together with the different interpretations of the "cap provision" and the application thereof. The abovementioned decision of the SCA on the most appropriate interpretation is then critically analysed. It is argued that the court, in Sweatman, misunderstood the implication of its decision and was therefore incapable of interpreting the provision correctly. The effect is that one of the primary purposes of the Amendment Act is circumvented.

  11. Mobilized peripheral blood stem cells provide rapid reconstitution but impaired long-term engraftment in a mouse model

    NARCIS (Netherlands)

    Yeoh, J. S. G.; Ausema, A.; Wierenga, P.; de Haan, G.; van Os, R.

    In this study, we use competitive repopulation to compare the quality and frequency of stem cells isolated from mobilized blood with stem cells isolated from bone marrow (BM) in a mouse model. Lin(-)Sca-1(+)c-Kit(+) (LSK) cells were harvested from control BM and peripheral blood of mice following

  12. An open-source software package for multivariate modeling and clustering: applications to air quality management.

    Science.gov (United States)

    Wang, Xiuquan; Huang, Guohe; Zhao, Shan; Guo, Junhong

    2015-09-01

    This paper presents an open-source software package, rSCA, which is developed based upon a stepwise cluster analysis method and serves as a statistical tool for modeling the relationships between multiple dependent and independent variables. The rSCA package is efficient in dealing with both continuous and discrete variables, as well as nonlinear relationships between the variables. It divides the sample sets of dependent variables into different subsets (or subclusters) through a series of cutting and merging operations based upon the theory of multivariate analysis of variance (MANOVA). The modeling results are given by a cluster tree, which includes both intermediate and leaf subclusters as well as the flow paths from the root of the tree to each leaf subcluster specified by a series of cutting and merging actions. The rSCA package is a handy and easy-to-use tool and is freely available at http://cran.r-project.org/package=rSCA . By applying the developed package to air quality management in an urban environment, we demonstrate its effectiveness in dealing with the complicated relationships among multiple variables in real-world problems.

  13. Tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors are the cellular source of fibrofatty infiltration in arrhythmogenic cardiomyopathy [v1; ref status: indexed, http://f1000r.es/17s

    Directory of Open Access Journals (Sweden)

    Ben Paylor

    2013-06-01

    Full Text Available Arrhythmogenic cardiomyopathy (AC is a disease of the heart involving myocardial dystrophy leading to fibrofatty scarring of the myocardium and is associated with an increased risk of both ventricular arrhythmias and sudden cardiac death. It often affects the right ventricle but may also involve the left. Although there has been significant progress in understanding the role of underlying desmosomal genetic defects in AC, there is still a lack of data regarding the cellular processes involved in its progression. The development of cardiac fibrofatty scarring is known to be a principal pathological process associated with ventricular arrhythmias, and it is vital that we elucidate the role of various cell populations involved in the disease if targeted therapeutics are to be developed. The known role of mesenchymal progenitor cells in the reparative process of both the heart and skeletal muscle has provided inspiration for the identification of the cellular basis of fibrofatty infiltration in AC. Here we hypothesize that reparative processes triggered by myocardial degeneration lead to the differentiation of tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors into adipocytes and fibroblasts, which compose the fibrofatty lesions characteristic of AC.

  14. Characterizing biogenous sediments using multibeam echosounder backscatter data - Estimating power law parameter utilizing various models

    Digital Repository Service at National Institute of Oceanography (India)

    Chakraborty, B.; Kodagali, V.N.

    ] for multibeam- Sca Beam system Sufficient acoustic pings were collected from each area when ship was stopped for sediment sampling Backscatter and geological sample data collections are made at ocanographically important sites from Southern Oceans. Agulhas... data collection was carried out at a station when ship was stopped for sediment core sampling, and this arrangement of data collection assured the statistical homogeneity ot backscatter data. MODELS USED We present two models, namely, the composite...

  15. Treatment with a Ginkgo biloba extract, EGb 761, inhibits excitotoxicity in an animal model of spinocerebellar ataxia type 17

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    Huang DS

    2016-02-01

    Full Text Available Ding-Siang Huang,1,* Hsuan-Yuan Lin,1,2,* Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li,1 Chung-Hsin Wu,1 Jung-Yaw Lin1,21Department of Life Science, National Taiwan Normal University, 2Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei City, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Spinocerebellar ataxia type 17 (SCA 17 is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.Keywords: spinocerebellar ataxia type 17, excitotoxicity, EGb 761, polyQ diseases, apoptosis 

  16. The Appellate Division has spoken – Sequestration Proceedings do not Qualify as Proceedings to Enforce a Credit Agreement under The National Credit Act 34 of 2005: Naidoo v ABSA Bank 2010 4 SA 597 (SCA

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    N Maghembe

    2011-05-01

    Full Text Available This case note aims to analyse the decision of the Supreme Court of Appeal in Naidoo v ABSA Bank 2010 4 SA 597 (SCA and to spark some debate as to whether being under debt review in terms of the National Credit Act (NCA should bar sequestration proceedings in the form of an application for the compulsory sequestration of a consumer’s estate. This decision held that a credit provider does not need to comply with the procedure provided for in section 129(1 of the NCA before instituting sequestration proceedings against a debtor, as such proceedings are not proceedings to enforce a credit agreement. The main issues discussed in this article are whether the court was correct in its interpretation of the relevant provisions of the NCA and whether this decision that allows a creditor to sequestrate a debtor who is attempting to meet his/her obligations under debt review, without informing him/her, is consistent with the principle urging consumers to satisfy all of their financial obligations under the NCA. It is submitted by the author that the court was correct in its interpretation of the relevant provisions of the NCA, but may have overlooked how this decision may impact the principle of satisfaction by the consumer of all of his/her financial obligations. It is suggested by the author that amendments be made to force the creditor to give a section 129 notice to the debtor before seeking sequestration of his/her estate. The author also suggests that once debt restructuring has been granted, credit providers should not be allowed to proceed with sequestration proceedings against the debtor.

  17. Flash-flood potential assessment and mapping by integrating the weights-of-evidence and frequency ratio statistical methods in GIS environment - case study: Bâsca Chiojdului River catchment (Romania)

    Science.gov (United States)

    Costache, Romulus; Zaharia, Liliana

    2017-06-01

    Given the significant worldwide human and economic losses caused due to floods annually, reducing the negative consequences of these hazards is a major concern in development strategies at different spatial scales. A basic step in flood risk management is identifying areas susceptible to flood occurrences. This paper proposes a methodology allowing the identification of areas with high potential of accelerated surface run-off and consequently, of flash-flood occurrences. The methodology involves assessment and mapping in GIS environment of flash flood potential index (FFPI), by integrating two statistical methods: frequency ratio and weights-of-evidence. The methodology was applied for Bâsca Chiojdului River catchment (340 km2), located in the Carpathians Curvature region (Romania). Firstly, the areas with torrential phenomena were identified and the main factors controlling the surface run-off were selected (in this study nine geographical factors were considered). Based on the features of the considered factors, many classes were set for each of them. In the next step, the weights of each class/category of the considered factors were determined, by identifying their spatial relationships with the presence or absence of torrential phenomena. Finally, the weights for each class/category of geographical factors were summarized in GIS, resulting the FFPI values for each of the two statistical methods. These values were divided into five classes of intensity and were mapped. The final results were used to estimate the flash-flood potential and also to identify the most susceptible areas to this phenomenon. Thus, the high and very high values of FFPI characterize more than one-third of the study catchment. The result validation was performed by (i) quantifying the rate of the number of pixels corresponding to the torrential phenomena considered for the study (training area) and for the results' testing (validating area) and (ii) plotting the ROC (receiver operating

  18. Impact of Frailty and Other Geriatric Syndromes on Clinical Management and Outcomes in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndromes: Rationale and Design of the LONGEVO-SCA Registry.

    Science.gov (United States)

    Alegre, Oriol; Ariza-Solé, Albert; Vidán, María T; Formiga, Francesc; Martínez-Sellés, Manuel; Bueno, Héctor; Sanchís, Juan; López-Palop, Ramón; Abu-Assi, Emad; Cequier, Àngel

    2016-07-01

    The incidence of acute coronary syndromes (ACS) is high in the elderly. Despite a high prevalence of frailty and other aging-related variables, little information exists about the optimal clinical management in patients with coexisting geriatric syndromes. The aim of the LONGEVO-SCA registry (Impacto de la Fragilidad y Otros Síndromes Geriátricos en el Manejo y Pronóstico Vital del Anciano con Síndrome Coronario Agudo sin Elevación de Segmento ST) is to assess the impact of aging-related variables on clinical management, prognosis, and functional status in elderly patients with ACS. A series of 500 consecutive octogenarian patients with non-ST-segment elevation ACS from 57 centers in Spain will be included. A comprehensive geriatric assessment will be performed during the admission, assessing functional status (Barthel Index, Lawton-Brody Index), frailty (FRAIL scale, Short Physical Performance Battery), comorbidity (Charlson Index), nutritional status (Mini Nutritional Assessment-Short Form), and quality of life (Seattle Angina Questionnaire). Patients will be managed according to current recommendations. The primary outcome will be the description of mortality and its causes at 6 months. Secondary outcomes will be changes in functional status and quality of life. Results from this study might significantly improve the knowledge about the impact of aging-related variables on management and outcomes of elderly patients with ACS. Clinical management of these patients has become a major health care problem due to the growing incidence of ACS in the elderly and its particularities. © 2016 Wiley Periodicals, Inc.

  19. Augmenting SCA project management and automation framework

    Science.gov (United States)

    Iyapparaja, M.; Sharma, Bhanupriya

    2017-11-01

    In our daily life we need to keep the records of the things in order to manage it in more efficient and proper way. Our Company manufactures semiconductor chips and sale it to the buyer. Sometimes it manufactures the entire product and sometimes partially and sometimes it sales the intermediary product obtained during manufacturing, so for the better management of the entire process there is a need to keep the track record of all the entity involved in it. Materials and Methods: Therefore to overcome with the problem the need raised to develop the framework for the maintenance of the project and for the automation testing. Project management framework provides an architecture which supports in managing the project by marinating the records of entire requirements, the test cases that were created for testing each unit of the software, defect raised from the past years. So through this the quality of the project can be maintained. Results: Automation framework provides the architecture which supports the development and implementation of the automation test script for the software testing process. Conclusion: For implementing project management framework the product of HP that is Application Lifecycle management is used which provides central repository to maintain the project.

  20. Snow cover characteristics in a glacierized catchment in the Tyrolean Alps - Improved spatially distributed modelling by usage of Lidar data

    Science.gov (United States)

    Schöber, Johannes; Schneider, K.; Helfricht, K.; Schattan, P.; Achleitner, S.; Schöberl, F.; Kirnbauer, R.

    2014-11-01

    In the present paper multi-temporal Lidar (Light detection and ranging) data and Landsat images are used to assess the spatial variability of snow at the end of the accumulation season (April-May) in a glacierized catchment (167 km2) in Tyrol, Austria. Snow cover characteristics in the Tyrolean Alps have been analysed using regular snow measurements and snow course data. Results are used for the conversion of basin-wide Lidar snow depth into snow water equivalent (SWE). When considering different possible error sources, uncertainties of the mean basin-wide SWE obtained from Lidar are between 12% and 16%. Available distributions of SWE and snow covered area (SCA) in the catchment are used for the calibration and validation of the fully distributed hydrological model SES. The study focuses especially on the simulation of snow accumulation and the corresponding variability of snow. Observed accumulation patterns are related to the topography (elevation, slope and curvature), and according parameter settings of the hydrological model are derived by means of Monte Carlo simulations. The majority of the model runs simulates SCA for various datasets with an accuracy of 85-95%. The paper demonstrates that using SWE data is superior to SCA for constraining model parameter ranges. Results at the watershed scale are in agreement with respect to the total water volume of the snow cover with deviations lower than 5% between SWE from Lidar or from the hydrological model.

  1. Influência da adulteração de combustíveis no desempenho e na vida útil de motores de combustão interna de ignição por faísca de pequeno porte utilizados em motocicletas.

    OpenAIRE

    Luiz Vicente Figueira de Mello Filho

    2009-01-01

    Este trabalho tem como principal objetivo mostrar os efeitos do uso de gasolina adulterada em motores de pequena cilindrada em seus desempenhos e durabilidades. Para tanto, foram realizados ensaios comparativos em três motores carburados de aplicação em motocicletas, de mesmas séries. Estes motores consumiram gasolina C, padrão brasileiro de combustível para motores de ignição por faísca, e misturas desta gasolina com etanol hidratado carburante e solvente C-9. Os resultados mostram alteraçõe...

  2. High spatial resolution radiation budget for Europe: derived from satellite data, validation of a regional model; Raeumlich hochaufgeloeste Strahlungsbilanz ueber Europa: Ableitung aus Satellitendaten, Validation eines regionalen Modells

    Energy Technology Data Exchange (ETDEWEB)

    Hollmann, R. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Atmosphaerenphysik

    2000-07-01

    Since forty years instruments onboard satellites have been demonstrated their usefulness for many applications in the field of meteorology and oceanography. Several experiments, like ERBE, are dedicated to establish a climatology of the global Earth radiation budget at the top of the atmosphere. Now the focus has been changed to the regional scale, e.g. GEWEX with its regional sub-experiments like BALTEX. To obtain a regional radiation budget for Europe in the first part of the work the well calibrated measurements from ScaRaB (scanner for radiation budget) are used to derive a narrow-to-broadband conversion, which is applicable to the AVHRR (advanced very high resolution radiometer). It is shown, that the accuracy of the method is in the order of that from SCaRaB itself. In the second part of the work, results of REMO have been compared with measurements of ScaRaB and AVHRR for March 1994. The model reproduces the measurements overall well, but it is overestimating the cold areas and underestimating the warm areas in the longwave spectral domain. Similarly it is overestimating the dark areas and underestimating the bright areas in the solar spectral domain. (orig.)

  3. Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia.

    Directory of Open Access Journals (Sweden)

    Jianxun Lei

    Full Text Available Pain is a hallmark feature of sickle cell anemia (SCA but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct "knock-in" strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.

  4. Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia

    Science.gov (United States)

    Lei, Jianxun; Benson, Barbara; Tran, Huy; Ofori-Acquah, Solomon F.; Gupta, Kalpna

    2016-01-01

    Pain is a hallmark feature of sickle cell anemia (SCA) but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R) treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct “knock-in” strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain. PMID:27494522

  5. Torpedo formation and Purkinje cell loss: modeling their relationship in cerebellar disease.

    Science.gov (United States)

    Louis, Elan D; Kuo, Sheng-Han; Vonsattel, Jean-Paul G; Faust, Phyllis L

    2014-08-01

    Torpedo formation and Purkinje cell (PC) loss represent standard and inter-related cerebellar responses to injury. Surprisingly, the nature of their relationship has not been carefully characterized across a range of normal and disease states. Are brains with more torpedoes expected to have fewer PCs? We quantified torpedoes and PCs in four groups: essential tremor (ET), spinocerebellar ataxia (SCA), multiple system atrophy-cerebellar (MSA-C), and controls. Brains from 100 individuals (58 ET, 27 controls, 7 SCA, 8 MSA-C) were available at the New York Brain Bank. After complete neuropathological assessment, a standard parasagittal neocerebellar block was harvested; a 7-μm thick section was stained with Luxol fast blue/hematoxylin and eosin; and torpedoes and PCs were quantified. For a given PC count, SCA and MSA-C cases often had higher torpedo counts than ET cases or controls. Furthermore, the relationship between torpedo and PC counts was complex. The correlation between torpedo and PC counts was negative in ET cases (i.e., individuals with more torpedoes had fewer PCs [i.e., more PC loss]) whereas the relationship was positive in MSA-C cases (i.e., individuals with fewer PCs [i.e., more PC loss] had fewer torpedoes). Patients with SCA showed both patterns. When all diagnostic groups were combined, the correlation was best fit by a quadratic (i.e., parabolic) model rather than a simple linear model; this model incorporated data on the negative correlation in ET cases, the mixed results in SCA cases, and the positive correlation in MSA-C cases (r = 0.636). The relationship between torpedo and PC counts was complex and heterogeneous across a range of cerebellar disease states, and was best characterized by a quadratic rather than a simple model. With more severe cerebellar disease, torpedoes can be quite numerous and are likely a common feature of surviving PCs, but eventually, dramatic loss of PC leads to a paradoxical reduction in observable torpedoes.

  6. Home-cage anxiety levels in a transgenic rat model for Spinocerebellar ataxia type 17 measured by an approach-avoidance task: The light spot test.

    Science.gov (United States)

    Kyriakou, Elisavet I; Nguyen, Huu Phuc; Homberg, Judith R; Van der Harst, Johanneke E

    2017-08-18

    Measuring anxiety in a reliable manner is essential for behavioural phenotyping of rodent models such as the rat model for Spinocerebellar ataxia type 17 (SCA17) where anxiety is reported in patients. An automated tool for assessing anxiety within the home cage can minimize human intervention, stress of handling, transportation and novelty. We applied the anxiety test "light spot" (LS) (white led directed at the food-hopper) to our transgenic SCA17 rat model in the PhenoTyper 4500 ® to extend the knowledge of this automated tool for behavioural phenotyping and to verify an anxiety-like phenotype at three different disease stages for use in future therapeutic studies. Locomotor activity was increased in SCA17 rats at 6 and 9 months during the first 15min of the LS, potentially reflecting increased risk assessment. Both genotypes responded to the test with lower duration in the LS zone and higher time spent inside the shelter compared to baseline. We present the first data of a rat model subjected to the LS. The LS can be considered more biologically relevant than a traditional test as it measures anxiety in a familiar situation. The LS successfully evoked avoidance and shelter-seeking in rats. SCA17 rats showed a stronger approach-avoidance conflict reflected by increased activity in the area outside the LS. This home cage test, continuously monitoring pre- and post-effects, provides the opportunity for in-depth analysis, making it a potentially useful tool for detecting subtle or complex anxiety-related traits in rodents. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Plant model of KIPT neutron source facility simulator

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Yan [Argonne National Lab. (ANL), Argonne, IL (United States); Wei, Thomas Y. [Argonne National Lab. (ANL), Argonne, IL (United States); Grelle, Austin L. [Argonne National Lab. (ANL), Argonne, IL (United States); Gohar, Yousry [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-02-01

    Argonne National Laboratory (ANL) of the United States and Kharkov Institute of Physics and Technology (KIPT) of Ukraine are collaborating on constructing a neutron source facility at KIPT, Kharkov, Ukraine. The facility has 100-kW electron beam driving a subcritical assembly (SCA). The electron beam interacts with a natural uranium target or a tungsten target to generate neutrons, and deposits its power in the target zone. The total fission power generated in SCA is about 300 kW. Two primary cooling loops are designed to remove 100-kW and 300-kW from the target zone and the SCA, respectively. A secondary cooling system is coupled with the primary cooling system to dispose of the generated heat outside the facility buildings to the atmosphere. In addition, the electron accelerator has a low efficiency for generating the electron beam, which uses another secondary cooling loop to remove the generated heat from the accelerator primary cooling loop. One of the main functions the KIPT neutron source facility is to train young nuclear specialists; therefore, ANL has developed the KIPT Neutron Source Facility Simulator for this function. In this simulator, a Plant Control System and a Plant Protection System were developed to perform proper control and to provide automatic protection against unsafe and improper operation of the facility during the steady-state and the transient states using a facility plant model. This report focuses on describing the physics of the plant model and provides several test cases to demonstrate its capabilities. The plant facility model uses the PYTHON script language. It is consistent with the computer language of the plant control system. It is easy to integrate with the simulator without an additional interface, and it is able to simulate the transients of the cooling systems with system control variables changing on real-time.

  8. Polyglutamine length-dependent toxicity from α1ACT in Drosophila models of spinocerebellar ataxia type 6

    Directory of Open Access Journals (Sweden)

    Wei-Ling Tsou

    2016-12-01

    Full Text Available Spinocerebellar ataxia type 6 (SCA6 is a neurodegenerative disease that results from abnormal expansion of a polyglutamine (polyQ repeat. SCA6 is caused by CAG triplet repeat expansion in the gene CACNA1A, resulting in a polyQ tract of 19-33 in patients. CACNA1A, a bicistronic gene, encodes the α1A calcium channel subunit and the transcription factor, α1ACT. PolyQ expansion in α1ACT causes degeneration in mice. We recently described the first Drosophila models of SCA6 that express α1ACT with a normal (11Q or hyper-expanded (70Q polyQ. Here, we report additional α1ACT transgenic flies, which express full-length α1ACT with a 33Q repeat. We show that α1ACT33Q is toxic in Drosophila, but less so than the 70Q version. When expressed everywhere, α1ACT33Q-expressing adults die earlier than flies expressing the normal allele. α1ACT33Q causes retinal degeneration and leads to aggregated species in an age-dependent manner, but at a slower pace than the 70Q counterpart. According to western blots, α1ACT33Q localizes less readily in the nucleus than α1ACT70Q, providing clues into the importance of polyQ tract length on α1ACT localization and its site of toxicity. We expect that these new lines will be highly valuable for future work on SCA6.

  9. Genes principais e genes predisponentes à doença de Parkinson : estudo sobre os genes PARK2, PARK6, PARK7, PARK8, SCA1, SCA2, SCA3, SCA6, SCA7 e o gene da glucocerebrosidase

    OpenAIRE

    Mariana Peixoto Socal

    2008-01-01

    A doença de Parkinson é freqüente no mundo todo, atingindo indivíduos de todas as idades e etnias. Embora comum e muito estudada, seus mecanismos causais ainda não são plenamente conhecidos e ainda não há tratamento curativo. Atualmente, são conhecidos alguns fatores ambientais e genéticos associados ao desenvolvimento da doença de Parkinson. Dentre os fatores genéticos, foram identificados diversos genes que podem, ou determinar a ocorrência da doença de forma mendeliana (genes principais), ...

  10. Segmentation of the Cerebellar Peduncles Using a Random Forest Classifier and a Multi-object Geometric Deformable Model: Application to Spinocerebellar Ataxia Type 6.

    Science.gov (United States)

    Ye, Chuyang; Yang, Zhen; Ying, Sarah H; Prince, Jerry L

    2015-07-01

    The cerebellar peduncles, comprising the superior cerebellar peduncles (SCPs), the middle cerebellar peduncle (MCP), and the inferior cerebellar peduncles (ICPs), are white matter tracts that connect the cerebellum to other parts of the central nervous system. Methods for automatic segmentation and quantification of the cerebellar peduncles are needed for objectively and efficiently studying their structure and function. Diffusion tensor imaging (DTI) provides key information to support this goal, but it remains challenging because the tensors change dramatically in the decussation of the SCPs (dSCP), the region where the SCPs cross. This paper presents an automatic method for segmenting the cerebellar peduncles, including the dSCP. The method uses volumetric segmentation concepts based on extracted DTI features. The dSCP and noncrossing portions of the peduncles are modeled as separate objects, and are initially classified using a random forest classifier together with the DTI features. To obtain geometrically correct results, a multi-object geometric deformable model is used to refine the random forest classification. The method was evaluated using a leave-one-out cross-validation on five control subjects and four patients with spinocerebellar ataxia type 6 (SCA6). It was then used to evaluate group differences in the peduncles in a population of 32 controls and 11 SCA6 patients. In the SCA6 group, we have observed significant decreases in the volumes of the dSCP and the ICPs and significant increases in the mean diffusivity in the noncrossing SCPs, the MCP, and the ICPs. These results are consistent with a degeneration of the cerebellar peduncles in SCA6 patients.

  11. A Bayesian spatial assimilation scheme for snow coverage observations in a gridded snow model

    Directory of Open Access Journals (Sweden)

    S. Kolberg

    2006-01-01

    Full Text Available A method for assimilating remotely sensed snow covered area (SCA into the snow subroutine of a grid distributed precipitation-runoff model (PRM is presented. The PRM is assumed to simulate the snow state in each grid cell by a snow depletion curve (SDC, which relates that cell's SCA to its snow cover mass balance. The assimilation is based on Bayes' theorem, which requires a joint prior distribution of the SDC variables in all the grid cells. In this paper we propose a spatial model for this prior distribution, and include similarities and dependencies among the grid cells. Used to represent the PRM simulated snow cover state, our joint prior model regards two elevation gradients and a degree-day factor as global variables, rather than describing their effect separately for each cell. This transformation results in smooth normalised surfaces for the two related mass balance variables, supporting a strong inter-cell dependency in their joint prior model. The global features and spatial interdependency in the prior model cause each SCA observation to provide information for many grid cells. The spatial approach similarly facilitates the utilisation of observed discharge. Assimilation of SCA data using the proposed spatial model is evaluated in a 2400 km2 mountainous region in central Norway (61° N, 9° E, based on two Landsat 7 ETM+ images generalized to 1 km2 resolution. An image acquired on 11 May, a week before the peak flood, removes 78% of the variance in the remaining snow storage. Even an image from 4 May, less than a week after the melt onset, reduces this variance by 53%. These results are largely improved compared to a cell-by-cell independent assimilation routine previously reported. Including observed discharge in the updating information improves the 4 May results, but has weak effect on 11 May. Estimated elevation gradients are shown to be sensitive to informational deficits occurring at high altitude, where snowmelt has not started

  12. Gestão do Conhecimento – GC – como recurso estratégico e fonte de Vantagem Competitiva Sustentável – VCS – na perspectiva Resource-based view – RBV – Knowledge Management – KM – used as a strategic resource and source of Sustainable Competitive Advantage – SCA – in the Resource-based view – RBV –

    Directory of Open Access Journals (Sweden)

    Virginia Aparecida Castro

    2012-06-01

    Full Text Available A Gestão do Conhecimento – GC – busca integrar toda a organização ao conhecimento que pode ser criado, compartilhado e armazenado. Desta forma, este trabalho tem por objetivo evidenciar de que maneira a GC é utilizada como recurso estratégico e fonte de Vantagem Competitiva Sustentável – VCS – na perspectiva Resource based view – RBV –. É feito um levantamento na forma de censo junto aos alunos das turmas de pós-graduação lato sensu (MBA da FAGEN – Faculdade de Gestão e Negócios – da UFU – Universidade Federal de Uberlândia –, os quais atuam no mercado como gestores e possuem pelo menos um subordinado sob a sua liderança. Após uma revisão da literatura sobre GC e VCS estruturou-se o instrumento de pesquisa a partir do Diagnóstico de Gestão do Conhecimento criado por Bukowitz e Williams (2002 e do Framework VRIO proposto por Barney (1991,1995. Ao considerar o critério de desempenho global de 55%, o cálculo da média aponta um percentual de 70%. Porém, a GC é utilizada em um nível preliminar, pois nota-se que os gestores necessitam, além de reconhecerem a importância da GC, trabalharem para a sua efetiva implantação. Assim, a GC, alinhada ao plano estratégico global da empresa, poderá ser utilizada como recurso estratégico e fonte de VCS na perspectiva RBV.The Knowledge Management – KM – searches to integrate organization to the knowledge that can be created, shared and stored. This study aims to show how the KM is used as a strategic resource and source of Sustainable Competitive Advantage – SCA – in the Resource based view – RBV – perspective. We made a survey in the form of census with the students of  Master Business Administration – MBA of FAGEN – Faculdade de Gestão e Negócios – da UFU – Universidade Federal de Uberlândia –. This students are managers and have employees with your leadership. After a review of the literature on KM and SCA, we have structured the

  13. Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect and duration after intracisternal injection of magnesium sulfate solution in a canine subarachnoid hemorrhage model.

    Science.gov (United States)

    Mori, Kentaro; Yamamoto, Takuji; Miyazaki, Masahiro; Hara, Yasukazu; Aiko, Yasuhisa; Koike, Nobuhiro; Sakamoto, Shinsuke; Nakao, Yasuaki; Esaki, Takanori

    2011-04-01

    The optimal CSF Mg(++) concentration for vasodilation of spastic cerebral arteries after subarachnoid hemorrhage (SAH) and its duration are unknown. The temporal profile of the vasodilatory effect and optimal CSF Mg(++) concentration after the intracisternal injection of MgSO(4) solution were investigated in an SAH model in canines. Cerebral vasospasm was induced by experimental SAH using a 2-hemorrhage model in 26 female beagles. On Day 7, 0.5 ml/kg of 15, 10, 5, or 0 mmol/L MgSO(4) in Ringer solution was injected into the cerebellomedullary cistern. Angiography was performed on Day 1 (before SAH) and before and 1, 3, and 6 hours after the intracisternal injection on Day 7 to measure arterial diameters of the basilar artery (BA), superior cerebellar artery (SCA), and vertebral artery (VA). Cerebrospinal fluid Mg(++) was also measured at the same time. Arterial diameters of the BA, SCA, and VA were significantly decreased by vasospasm on Day 7. Arterial diameter ratios (ratio of arterial diameter after MgSO(4) injection to diameter before injection on Day 7) of the BA and SCA at 1 and 3 hours after and the VA at 1 hour after intracisternal injection of the MgSO(4) solution were positively correlated with the CSF Mg(++) concentration. All arterial diameter ratios, except 1 point of the SCA, exceeded 1 if the CSF Mg(++) concentration was > 3 mEq/L at 1 hour after injection. Animals with CSF Mg(++) concentrations > 3 mEq/L at 1 hour after injection (11 dogs) showed significantly increased arterial diameters of the BA at 1 and 3 hours after and of the SCA and VA at 1, 3, and 6 hours after injection, as compared with the diameters before injection. The CSF Mg(++) concentration significantly increased at 1 hour (3.73 ± 0.69 mEq/L, p 3 mEq/L. The vasodilatory effect continues for 3-6 hours after injection. These results suggest that the continuous infusion or intermittent intracisternal injection of MgSO(4) is needed to maintain the optimal CSF Mg(++) concentration and

  14. Spinocerebellar ataxia type 7 (SCA7: family princeps’ history, genealogy and geographical distribution Ataxia espinocerebelar do tipo 7 (AEC7: história, genealogia e distribuição geográfica da família princeps

    Directory of Open Access Journals (Sweden)

    Salomão da Cunha Linhares

    2006-06-01

    Full Text Available We conducted a 320 year retrospective survey of the history and genealogy of a large Brazilian family with SCA7. The ancestral couple was from the State of Ceará, Brazil, and the genealogical tree was composed of 577 individuals, including 217 males (37.6%, 255 females (44.1% and 105 individuals of unknown sex (18.1%. Based on collected information, the 118 individuals consistently affected were distributed in generations IV (n=2, V (n=28, VI (n=57, VII (n=25 and VIII (n=6 of the genealogical tree. Sixty affected members are alive, 37 of them (61.6% live in the Northeast region, 12 (20% in the Southeast, 9 (15% in the Center-West and 2 (3.3% in the North. This genealogical survey was based only on 4 of the 10 children of the ancestral couple since the destiny of the remaining 6 is unknown. We propose that other Brazilian families with SCA7 may have the same genetic origin.Avaliamos retrospectivamente 320 anos da história e da genealogia de uma família brasileira portadora de ataxia espinocerebelar do tipo 7 (AEC7. O casal ancestral é oriundo do Estado do Ceará e a árvore genealógica foi composta de 577 indivíduos, sendo 217 do sexo masculino (37,6%, 255 do sexo feminino (44,1% e 105 de sexo ignorado (18,1%. Até o presente momento, 118 indivíduos foram acometidos, distribuídos nas gerações IV (n=2, V (n=28, VI (n=57, VII (n=25 e VIII (n=6 da árvore genealógica. Entre os doentes atualmente vivos (n=60, 37 deles (61,6% encontram-se na região Nordeste, 12 (20% na região Sudeste, 9 (15% na região Centro-Oeste e 2 (3,3% na região Norte. Uma vez que a reconstituição da árvore genealógica foi baseada em apenas 4 dos 10 filhos do casal ancestral devido ao desconhecimento do destino dos outros 6, levantamos a hipótese de que outras famílias brasileiras com AEC7 possam ter a mesma origem genética.

  15. Estimation of the spatiotemporal dynamics of snow covered area by using cellular automata models

    Science.gov (United States)

    Pardo-Igúzquiza, Eulogio; Collados-Lara, Antonio-Juan; Pulido-Velazquez, David

    2017-07-01

    Given the need to consider the cryosphere in water resources management for mountainous regions, the purpose of this paper is to model the daily spatially distributed dynamics of snow covered area (SCA) by using calibrated cellular automata models. For the operational use of the calibrated model, the only data requirements are the altitude of each cell of the spatial discretization of the area of interest and precipitation and temperature indexes for the area of interest. For the calibration step, experimental snow covered area data are needed. Potential uses of the model are to estimate the snow covered area when satellite data are absent, or when they provide a temporal resolution different from the operational resolution, or when the satellite images are useless because they are covered by clouds or because there has been a sensor failure. Another interesting application is the simulation of SCA dynamics for the snow covered area under future climatic scenarios. The model is applied to the Sierra Nevada mountain range, in southern Spain, which is home to significant biodiversity, contains important water resources in its snowpack, and contains the most meridional ski resort in Europe.

  16. Contribution of high resolution remote sensing data to the modeling of the snow cover the in Atlas Mountains

    Science.gov (United States)

    Baba, Wassim; Gascoin, Simon; Hanich, Lahoucine; Kinnard, Christophe

    2017-04-01

    Snow melt from the Atlas Mountains watersheds represent an important water resource for the semi-arid, cultivated, lowlands. Due to the high incoming solar radiation and low precipitation, the spatial-temporal variability of the snowpack is expected to be strongly influenced by the topography. We explore this hypothesis using a distributed energy balance snow model (SnowModel) in the experimental watershed of the Rheraya River in Morocco (225 km2). The digital elevation model (DEM) in SnowModel is used for the computation of the gridded meteorological forcing from the automatic weather stations data. We acquired three Pléiades stereo pairs in to produce an accurate, high resolution DEM of the Rheraya watershed at 4 m posting. Then, the DEM was resampled to different spatial resolutions (8 m, 30 m, 90 m, 250 m and 500 m) to simulate the snowpack evolution over 2008-2009 snow season. As validation data we used a time series of 15 maps of the snow cover area (SCA) from Formosat-2 imagery over the same snow season in the upper Rheraya watershed. These maps have a resolution of 8 m, which enables to capture small-scale variability in the snow cover. We found that the simulations at 90 m, 30 m and 8 m yield similar results at the catchment scale, with significant differences in areas of very steep topography only. From February to April, an overall good agreement was observed between the simulated SCA and the Formosat-2 SCA at 8 m and 90 m. Before the melting season, true positive (TP) column of confusion matrix is close to 1, but it drops to 0.6 during the melting season. Heidke Skill Score is higher than 0.7 for the most of the validation dates and averages 0.8. On the contrary, 500 m simulation underestimates the SCA throughout the snow season and the TP score is always inferior to the one obtained at 8 m and 90 m. We further analyzed the effect of topography by comparing the distribution of meteorological and snowpack variables along north-south and east

  17. Model.

    OpenAIRE

    Zachary Patterson

    2008-01-01

    Social scientists appear to be divided into two camps: those who use models and those who do not. In order to understand this phenomenon, a clear understanding of what a model is is required. Unfortunately, this is more complicated than one might think. To be sure, few social scientists would have trouble identifying what they consider to be a model: defining what a model is, however, is more difficult. To echo Associate Justice Potter Stewart's famous quote about pornography, most social...

  18. BMP-non-responsive Sca1+ CD73+ CD44+ mouse bone marrow derived osteoprogenitor cells respond to combination of VEGF and BMP-6 to display enhanced osteoblastic differentiation and ectopic bone formation.

    Directory of Open Access Journals (Sweden)

    Vedavathi Madhu

    Full Text Available Clinical trials on fracture repair have challenged the effectiveness of bone morphogenetic proteins (BMPs but suggest that delivery of mesenchymal stem cells (MSCs might be beneficial. It has also been reported that BMPs could not increase mineralization in several MSCs populations, which adds ambiguity to the use of BMPs. However, an exogenous supply of MSCs combined with vascular endothelial growth factor (VEGF and BMPs is reported to synergistically enhance fracture repair in animal models. To elucidate the mechanism of this synergy, we investigated the osteoblastic differentiation of cloned mouse bone marrow derived MSCs (D1 cells in vitro in response to human recombinant proteins of VEGF, BMPs (-2, -4, -6, -9 and the combination of VEGF with BMP-6 (most potent BMP. We further investigated ectopic bone formation induced by MSCs pre-conditioned with VEGF, BMP-6 or both. No significant increase in mineralization, phosphorylation of Smads 1/5/8 and expression of the ALP, COL1A1 and osterix genes was observed upon addition of VEGF or BMPs alone to the cells in culture. The lack of CD105, Alk1 and Alk6 expression in D1 cells correlated with poor response to BMPs indicating that a greater care in the selection of MSCs is necessary. Interestingly, the combination of VEGF and BMP-6 significantly increased the expression of ALP, COL1A1 and osterix genes and D1 cells pre-conditioned with VEGF and BMP-6 induced greater bone formation in vivo than the non-conditioned control cells or the cells pre-conditioned with either VEGF or BMP-6 alone. This enhanced bone formation by MSCs correlated with higher CADM1 expression and OPG/RANKL ratio in the implants. Thus, combined action of VEGF and BMP on MSCs enhances osteoblastic differentiation of MSCs and increases their bone forming ability, which cannot be achieved through use of BMPs alone. This strategy can be effectively used for bone repair.

  19. Delay and Disruption Tolerant Networking MACHETE Model

    Science.gov (United States)

    Segui, John S.; Jennings, Esther H.; Gao, Jay L.

    2011-01-01

    To verify satisfaction of communication requirements imposed by unique missions, as early as 2000, the Communications Networking Group at the Jet Propulsion Laboratory (JPL) saw the need for an environment to support interplanetary communication protocol design, validation, and characterization. JPL's Multi-mission Advanced Communications Hybrid Environment for Test and Evaluation (MACHETE), described in Simulator of Space Communication Networks (NPO-41373) NASA Tech Briefs, Vol. 29, No. 8 (August 2005), p. 44, combines various commercial, non-commercial, and in-house custom tools for simulation and performance analysis of space networks. The MACHETE environment supports orbital analysis, link budget analysis, communications network simulations, and hardware-in-the-loop testing. As NASA is expanding its Space Communications and Navigation (SCaN) capabilities to support planned and future missions, building infrastructure to maintain services and developing enabling technologies, an important and broader role is seen for MACHETE in design-phase evaluation of future SCaN architectures. To support evaluation of the developing Delay Tolerant Networking (DTN) field and its applicability for space networks, JPL developed MACHETE models for DTN Bundle Protocol (BP) and Licklider/Long-haul Transmission Protocol (LTP). DTN is an Internet Research Task Force (IRTF) architecture providing communication in and/or through highly stressed networking environments such as space exploration and battlefield networks. Stressed networking environments include those with intermittent (predictable and unknown) connectivity, large and/or variable delays, and high bit error rates. To provide its services over existing domain specific protocols, the DTN protocols reside at the application layer of the TCP/IP stack, forming a store-and-forward overlay network. The key capabilities of the Bundle Protocol include custody-based reliability, the ability to cope with intermittent connectivity

  20. Models

    DEFF Research Database (Denmark)

    Juel-Christiansen, Carsten

    2005-01-01

    Artiklen fremhæver den visuelle rotation - billeder, tegninger, modeller, værker - som det privilligerede medium i kommunikationen af ideer imellem skabende arkitekter......Artiklen fremhæver den visuelle rotation - billeder, tegninger, modeller, værker - som det privilligerede medium i kommunikationen af ideer imellem skabende arkitekter...

  1. [The broad phenotypic spectrum of SCA-3: hereditary spastic paraplegia].

    Science.gov (United States)

    Rodríguez-Quiroga, Sergio A; González-Morón, Dolores; Arakaki, Tomoko; Garreto, Nélida; Kauffman, Marcelo A

    2013-01-01

    Machado-Joseph disease (MJD) is the most frequent dominantly inherited spinocerebellar ataxia. A marked phenotypic variability is a characteristic of this disorder that could involve non-cerebellar presentations. Based on several case reports describing pyramidal dysfunction as the main symptom at onset, a clinical form resembling hereditary spastic paraplegia has been proposed. We report here two further cases of MJD patients whose initial clinical presentation suggested hereditary spastic paraplegia, and a summary of the main findings of previously similar published reports. Our findings lent support to the proposal of a MJD subtype distinguished by a marked pyramidal dysfunction at onset, simulating a clinical picture of hereditary spastic paraplegia.

  2. Bokolo v S 2014 (1) SACR 66 (SCA)

    African Journals Online (AJOL)

    Public Law at the University of Pretoria. The author gratefully acknowledges the insights of Edward M ... prosecution of criminals if it is used in the appropriate context. The relevance of DNA evidence lies in its potential to ... criminal prosecutions, including cases of homicide and sexual offences. Over the years the science.

  3. PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype.

    NARCIS (Netherlands)

    Visser, J.E.; Bloem, B.R.; Warrenburg, B.P.C. van de

    2007-01-01

    Progressive myoclonic ataxia, also referred to as Ramsay Hunt syndrome, is characterized by a combination of myoclonus and cerebellar ataxia, infrequently accompanied by tonic-clonic seizures. Its differential diagnosis overlaps with progressive myoclonic epilepsy, a syndrome with myoclonus,

  4. SCaN Testbed Software Development and Lessons Learned

    Science.gov (United States)

    Kacpura, Thomas J.; Varga, Denise M.

    2012-01-01

    National Aeronautics and Space Administration (NASA) has developed an on-orbit, adaptable, Software Defined Radio (SDR)Space Telecommunications Radio System (STRS)-based testbed facility to conduct a suite of experiments to advance technologies, reduce risk, and enable future mission capabilities on the International Space Station (ISS). The SCAN Testbed Project will provide NASA, industry, other Government agencies, and academic partners the opportunity to develop and field communications, navigation, and networking technologies in the laboratory and space environment based on reconfigurable, SDR platforms and the STRS Architecture.The SDRs are a new technology for NASA, and the support infrastructure they require is different from legacy, fixed function radios. SDRs offer the ability to reconfigure on-orbit communications by changing software for new waveforms and operating systems to enable new capabilities or fix any anomalies, which was not a previous option. They are not stand alone devices, but required a new approach to effectively control them and flow data. This requires extensive software to be developed to utilize the full potential of these reconfigurable platforms. The paper focuses on development, integration and testing as related to the avionics processor system, and the software required to command, control, monitor, and interact with the SDRs, as well as the other communication payload elements. An extensive effort was required to develop the flight software and meet the NASA requirements for software quality and safety. The flight avionics must be radiation tolerant, and these processors have limited capability in comparison to terrestrial counterparts. A big challenge was that there are three SDRs onboard, and interfacing with multiple SDRs simultaneously complicatesd the effort. The effort also includes ground software, which is a key element for both the command of the payload, and displaying data created by the payload. The verification of the software was an extensive effort. The challenges of specifying a suitable test matrix with reconfigurable systems that offer numerous configurations is highlighted. Since the flight system testing requires methodical, controlled testing that limits risk, a nearly identical ground system to the on-orbit flight system was required to develop the software and write verification procedures before it was installed and tested on the flight system. The development of the SCAN testbed was an accelerated effort to meet launch constraints, and this paper discusses tradeoffs made to balance needed software functionality and still maintain the schedule. Future upgrades are discussed that optimize the avionics and allow experimenters to utilize the SCAN testbed potential.

  5. Do we need a dynamic snow depth threshold when comparing hydrological models with remote sensing products in mountain catchments?

    Science.gov (United States)

    Engel, Michael; Bertoldi, Giacomo; Notarnicola, Claudia; Comiti, Francesco

    2017-04-01

    To assess the performance of simulated snow cover of hydrological models, it is common practice to compare simulated data with observed ones derived from satellite images such as MODIS. However, technical and methodological limitations such as data availability of MODIS products, its spatial resolution or difficulties in finding appropriate parameterisations of the model need to be solved previously. Another important assumption usually made is the threshold of minimum simulated snow depth, generally set to 10 mm of snow depth, to respect the MODIS detection thresholds for snow cover. But is such a constant threshold appropriate for complex alpine terrain? How important is the impact of different snow depth thresholds on the spatial and temporal distribution of the pixel-based overall accuracy (OA)? To address this aspect, we compared the snow covered area (SCA) simulated by the GEOtop 2.0 snow model to the daily composite 250 m EURAC MODIS SCA in the upper Saldur basin (61 km2, Eastern Italian Alps) during the period October 2011 - October 2013. Initially, we calibrated the snow model against snow depths and snow water equivalents at point scale, taken from measurements at different meteorological stations. We applied different snow depth thresholds (0 mm, 10 mm, 50 mm, and 100 mm) to obtain the simulated snow cover and assessed the changes in OA both in time (during the entire evaluation period, accumulation and melting season) and space (entire catchment and specific areas of topographic characteristics such as elevation, slope, aspect, landcover, and roughness). Results show remarkable spatial and temporal differences in OA with respect to different snow depth thresholds. Inaccuracies of simulated and observed SCA during the accumulation season September to November 2012 were located in areas with north-west aspect, slopes of 30° or little elevation differences at sub-pixel scale (-0.25 to 0 m). We obtained best agreements with MODIS SCA for a snow depth

  6. Modelling

    CERN Document Server

    Spädtke, P

    2013-01-01

    Modeling of technical machines became a standard technique since computer became powerful enough to handle the amount of data relevant to the specific system. Simulation of an existing physical device requires the knowledge of all relevant quantities. Electric fields given by the surrounding boundary as well as magnetic fields caused by coils or permanent magnets have to be known. Internal sources for both fields are sometimes taken into account, such as space charge forces or the internal magnetic field of a moving bunch of charged particles. Used solver routines are briefly described and some bench-marking is shown to estimate necessary computing times for different problems. Different types of charged particle sources will be shown together with a suitable model to describe the physical model. Electron guns are covered as well as different ion sources (volume ion sources, laser ion sources, Penning ion sources, electron resonance ion sources, and H$^-$-sources) together with some remarks on beam transport.

  7. Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

    OpenAIRE

    Elsayed, Solaf M.; Heller, Raoul; Thoenes, Michaela; Zaki, Maha S; Swan, Daniel; Elsobky, Ezzat; Zühlke, Christine; Ebermann, Inga; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno J.

    2014-01-01

    Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate w...

  8. Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations.

    Science.gov (United States)

    Elsayed, Solaf M; Heller, Raoul; Thoenes, Michaela; Zaki, Maha S; Swan, Daniel; Elsobky, Ezzat; Zühlke, Christine; Ebermann, Inga; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno J

    2014-02-01

    Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.

  9. The autophagy/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in mice

    NARCIS (Netherlands)

    Alves, Sandro; Cormier-Dequaire, Florence; Marinello, Martina; Marais, Thibaut; Muriel, Marie-Paule; Beaumatin, Florian; Charbonnier-Beaupel, Fanny; Tahiri, Khadija; Seilhean, Danielle; El Hachimi, Khalid; Ruberg, Merle; Stevanin, Giovanni; Barkats, Martine; den Dunnen, Wilfred; Priault, Muriel; Brice, Alexis; Durr, Alexandra; Corvol, Jean-Christophe; Sittler, Annie

    2014-01-01

    There is still no treatment for polyglutamine disorders, but clearance of mutant proteins might represent a potential therapeutic strategy. Autophagy, the major pathway for organelle and protein turnover, has been implicated in these diseases. To determine whether the autophagy/lysosome system

  10. Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia.

    Science.gov (United States)

    Stefanescu, Maria R; Dohnalek, Moritz; Maderwald, Stefan; Thürling, Markus; Minnerop, Martina; Beck, Andreas; Schlamann, Marc; Diedrichsen, Joern; Ladd, Mark E; Timmann, Dagmar

    2015-05-01

    Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values ataxia type 3. Within the cerebellar nuclei, reductions were significant when comparing spinocerebellar ataxia type 6 and Friedreich's ataxia to matched controls (P cerebellar nuclei in patients with Friedreich's ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia type 6, pathology was not restricted to the cerebellar cortex but also involved the cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand, revealed that pathology in Friedreich's ataxia and spinocerebellar ataxia type 3 is not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar cortex despite no or little structural changes. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. model

    African Journals Online (AJOL)

    distress, or culture—bound syndrome, not listed in DSM—lV. It may correspond to various DS/Vl-ll/ disorders, depending on its exact clinical presentation, e.g. dissociative disorder, adiustment disorder, or schizophrenia.1g As with other local idioms ot distress, the explanatory model takes precedence over the descriptive ...

  12. Chromosomal regions involved in hybrid performance and heterosis: their AFLP(R)-based identification and practical use in prediction models.

    Science.gov (United States)

    Vuylsteke, M; Kuiper, M; Stam, P

    2000-09-01

    In this paper, a novel approach towards the prediction of hybrid performance and heterosis is presented. Here, we describe an approach based on: (i) the assessment of associations between AFLP(R) markers and hybrid performance and specific combining ability (SCA) across a set of hybrids; and (ii) the assumption that the joint effect of genetic factors (loci) determined this way can be obtained by addition. Estimated gene effects for grain yield varied from additive, partial dominance to overdominance. This procedure was applied to 53 interheterotic hybrids out of a 13 by 13 half-diallel among maize inbreds, evaluated for grain yield. The hybrid value, representing the joint effect of the genetic factors, accounted for up to 62.4% of the variation in the hybrid performance observed, whereas the corresponding efficiency of the SCA model was 36.8%. Efficiency of the prediction for hybrid performance was evaluated by means of a cross-validation procedure for grain yield of (i) the 53 interheterotic hybrids and (ii) 16 hybrids partly related to the 13 by 13 half-diallel. Comparisons in prediction efficiency with the 'distance' model were made. Because the map position of the selected markers is known, putative quantitative trait loci (QTL) affecting grain yield, in terms of hybrid performance or heterosis, are identified. Some QTL of grain yield detected in the present study were located in the vicinity of loci reported earlier as having quantitative effects on grain yield.

  13. A model for the spatial distribution of snow water equivalent parameterized from the spatial variability of precipitation

    Directory of Open Access Journals (Sweden)

    T. Skaugen

    2016-09-01

    Full Text Available Snow is an important and complicated element in hydrological modelling. The traditional catchment hydrological model with its many free calibration parameters, also in snow sub-models, is not a well-suited tool for predicting conditions for which it has not been calibrated. Such conditions include prediction in ungauged basins and assessing hydrological effects of climate change. In this study, a new model for the spatial distribution of snow water equivalent (SWE, parameterized solely from observed spatial variability of precipitation, is compared with the current snow distribution model used in the operational flood forecasting models in Norway. The former model uses a dynamic gamma distribution and is called Snow Distribution_Gamma, (SD_G, whereas the latter model has a fixed, calibrated coefficient of variation, which parameterizes a log-normal model for snow distribution and is called Snow Distribution_Log-Normal (SD_LN. The two models are implemented in the parameter parsimonious rainfall–runoff model Distance Distribution Dynamics (DDD, and their capability for predicting runoff, SWE and snow-covered area (SCA is tested and compared for 71 Norwegian catchments. The calibration period is 1985–2000 and validation period is 2000–2014. Results show that SD_G better simulates SCA when compared with MODIS satellite-derived snow cover. In addition, SWE is simulated more realistically in that seasonal snow is melted out and the building up of "snow towers" and giving spurious positive trends in SWE, typical for SD_LN, is prevented. The precision of runoff simulations using SD_G is slightly inferior, with a reduction in Nash–Sutcliffe and Kling–Gupta efficiency criterion of 0.01, but it is shown that the high precision in runoff prediction using SD_LN is accompanied with erroneous simulations of SWE.

  14. Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging.

    Science.gov (United States)

    Li, Jing; Cai, Dachuan; Yao, Xin; Zhang, Yanyan; Chen, Linbo; Jing, Pengwei; Wang, Lu; Wang, Yaping

    2016-06-09

    Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1⁺ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1⁺ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16(Ink4a), Rb, p21(Cip1/Waf1) and p53 in senescent Sca-1⁺ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1⁺ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16(Ink4a)-Rb and p53-p21(Cip1/Waf1) signaling.

  15. Improving daily streamflow forecasts in mountainous Upper Euphrates basin by multi-layer perceptron model with satellite snow products

    Science.gov (United States)

    Uysal, Gökçen; Şensoy, Aynur; Şorman, A. Arda

    2016-12-01

    This paper investigates the contribution of Moderate Resolution Imaging Spectroradiometer (MODIS) satellite Snow Cover Area (SCA) product and in-situ snow depth measurements to Artificial Neural Network model (ANN) based daily streamflow forecasting in a mountainous river basin. In order to represent non-linear structure of the snowmelt process, Multi-Layer Perceptron (MLP) Feed-Forward Backpropagation (FFBP) architecture is developed and applied in Upper Euphrates River Basin (10,275 km2) of Turkey where snowmelt constitutes approximately 2/3 of total annual volume of runoff during spring and early summer months. Snowmelt season is evaluated between March and July; 7 years (2002-2008) seasonal daily data are used during training while 3 years (2009-2011) seasonal daily data are split for forecasting. One of the fastest ANN training algorithms, the Levenberg-Marquardt, is used for optimization of the network weights and biases. The consistency of the network is checked with four performance criteria: coefficient of determination (R2), Nash-Sutcliffe model efficiency (ME), root mean square error (RMSE) and mean absolute error (MAE). According to the results, SCA observations provide useful information for developing of a neural network model to predict snowmelt runoff, whereas snow depth data alone are not sufficient. The highest performance is experienced when total daily precipitation, average air temperature data are combined with satellite snow cover data. The data preprocessing technique of Discrete Wavelet Analysis (DWA) is coupled with MLP modeling to further improve the runoff peak estimates. As a result, Nash-Sutcliffe model efficiency is increased from 0.52 to 0.81 for training and from 0.51 to 0.75 for forecasting. Moreover, the results are compared with that of a conceptual model, Snowmelt Runoff Model (SRM), application using SCA as an input. The importance and the main contribution of this study is to use of satellite snow products and data

  16. Refining Distributed Snowmelt Models in a Mountain Environment

    Science.gov (United States)

    Deems, J. S.; Lott, F. C.; Lundquist, J. D.

    2008-12-01

    In the radiation-dominated snowmelt environment of the Tuolumne River basin in Yosemite National Park, California, we have observed that snowmelt models using explicit representations of the snow surface energy balance are superior to bulk temperature-index models for capturing spatial and temporal variations in snowmelt. In comparing a temperature-index model (Snow-17) with two energy-balance models (the Utah Energy Balance model - UEB and the Distributed Hydrology Soil Vegetation Model - DHSVM), we found that the details in melt timing necessary for ecosystem studies are best simulated using the energy balance models. Additionally, two model-derived variables, namely shortwave albedo and snowpack surface and internal temperatures, are critical to accurate estimation of snowmelt onset, spring melt volumes, and the timing of hydrograph recessions, including when ephemeral streams go dry. We examine model representations of these variables as implemented in UEB and DHSVM using comparisons with observed streamflow and MODIS snow-covered area (SCA) and albedo derived from the MODSCAG algorithms.

  17. Incorporation of a glacier and snow melting model with CREST to resolve alpine glaciers and snow melting

    Science.gov (United States)

    Chen, X.; Long, D.; Zeng, C.; Hong, Y.

    2016-12-01

    Dynamics of alpine glaciers and snow cover respond to global climate change notably, particularly over the Tibetan Plateau (TP) as the world's third pole where complex topography and lack of ground-based observations result in knowledge gaps in cryospheric processes and large uncertainties in model output. This study develops a snow and glacier melt model and coupled with a distributed hydrological model (Coupled Routing and Excess Storage model, CREST) using the upper Brahmaputra River basin in the TP as a case study. Satellite-based precipitation and land surface temperature are used as primary model forcing and a progressive two-stage calibration strategy is designed to derive model parameters by two steps, i.e., (1) the processes of snow melting and (2) glacier melting and runoff generation using multi-source remote sensing data. Calibration for the snow melting model is performed using snow cover area (SCA) and snow water equivalent (SWE) products combined with some in situ measurements. Calibration for glacier melting and runoff generation is based on remotely sensed total water storage (TWS) and observational streamflow records. Results indicate that sole consideration of the SCA or streamflow performance would result in significant degradation of the performance of SWE simulation and vice versa. The overestimated glacier and snow melting rates and their contribution to streamflow in previous studies were reexamined. This study could be valuable in studying the impacts of climate change on cryospheric regions and providing an improved approach for calibrating and simulating more accurate melting rates over the study basin and potentially similar regions globally.

  18. Dust Cloud Modeling and Propagation Effects for Radar and Communications Codes

    Science.gov (United States)

    1978-11-01

    more effort to include the mlt iple scatter build-’.) f’ctor, B Ii(_,) . ’Ihe current dust model assumes that the si z di str i but ion of the dust...I .I ~ IF r VJ Tr~ H’ T Hr C - IPL E x 1 J)Fy ;IF P EF ACT TIij I S £sSS’"F 1: 1 r N -N I *Iil -J r c Q SCA = SC AT T F P If FFICIfoCy, .1 TC H F L...Grant Office stu Space Science tab ATTN: K. BakerTr ’-, acn i ItjtjtFeATTN: L. Jensen n-.c A[ a. l claior’s Visidyne, Inc. _T 1 LeeATTIi: C. Humphrey

  19. Certification Study of a Derivative Model of a Small Jet Transport Airplane Using a Piloted Research Simulator

    Science.gov (United States)

    1977-06-01

    lation are compared in figure 5. Thrust was computed by the engine model progr am as a f un ct ion of Mach number, altitude , and throttle position . The...at the flight condition selected. The Model 758 was disturbed in yaw at a 1 tad/sec rate to determine Ct ~ and Cnr (fig. 8(b), “ROLL” and “YAW” boxes...The sca t te r in the s imula t ion data was due p r imar i ly to the p i lo ts ’ d i f f i - c u l t y in precisely m a i n t a i n i n g a s t

  20. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2011-11-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs. Our group has previously demonstrated that calcium (Ca2+ signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128. Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2 and spinocerebellar ataxia 3 (SCA3 mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that Ryan

  1. Modeling and Simulation of Phased Array Antennas to Support Next-Generation Satellite Design

    Science.gov (United States)

    Tchorowski, Nicole; Murawski, Robert; Manning, Robert; Fuentes, Michael

    2016-01-01

    Developing enhanced simulation capabilities has become a significant priority for the Space Communications and Navigation (SCaN) project at NASA as new space communications technologies are proposed to replace aging NASA communications assets, such as the Tracking and Data Relay Satellite System (TDRSS). When developing the architecture for these new space communications assets, it is important to develop updated modeling and simulation methodologies, such that competing architectures can be weighed against one another and the optimal path forward can be determined. There have been many simulation tools developed here at NASA for the simulation of single RF link budgets, or for the modeling and simulation of an entire network of spacecraft and their supporting SCaN network elements. However, the modeling capabilities are never fully complete and as new technologies are proposed, gaps are identified. One such gap is the ability to rapidly develop high fidelity simulation models of electronically steerable phased array systems. As future relay satellite architectures are proposed that include optical communications links, electronically steerable antennas will become more desirable due to the reduction in platform vibration introduced by mechanically steerable devices. In this research, we investigate how modeling of these antennas can be introduced into out overall simulation and modeling structure. The ultimate goal of this research is two-fold. First, to enable NASA engineers to model various proposed simulation architectures and determine which proposed architecture meets the given architectural requirements. Second, given a set of communications link requirements for a proposed satellite architecture, determine the optimal configuration for a phased array antenna. There is a variety of tools available that can be used to model phased array antennas. To meet our stated goals, the first objective of this research is to compare the subset of tools available to us

  2. Use of satellite-derived data for characterization of snow cover and simulation of snowmelt runoff through a distributed physically based model of runoff generation

    Directory of Open Access Journals (Sweden)

    L. S. Kuchment

    2010-02-01

    Full Text Available A technique of using satellite-derived data for constructing continuous snow characteristics fields for distributed snowmelt runoff simulation is presented. The satellite-derived data and the available ground-based meteorological measurements are incorporated in a physically based snowpack model. The snowpack model describes temporal changes of the snow depth, density and water equivalent (SWE, accounting for snow melt, sublimation, refreezing melt water and snow metamorphism processes with a special focus on forest cover effects. The remote sensing data used in the model consist of products include the daily maps of snow covered area (SCA and SWE derived from observations of MODIS and AMSR-E instruments onboard Terra and Aqua satellites as well as available maps of land surface temperature, surface albedo, land cover classes and tree cover fraction. The model was first calibrated against available ground-based snow measurements and then applied to calculate the spatial distribution of snow characteristics using satellite data and interpolated ground-based meteorological data. The satellite-derived SWE data were used for assigning initial conditions and the SCA data were used for control of snow cover simulation. The simulated spatial distributions of snow characteristics were incorporated in a distributed physically based model of runoff generation to calculate snowmelt runoff hydrographs. The presented technique was applied to a study area of approximately 200 000 km2 including the Vyatka River basin with catchment area of 124 000 km2. The correspondence of simulated and observed hydrographs in the Vyatka River are considered as an indicator of the accuracy of constructed fields of snow characteristics and as a measure of effectiveness of utilizing satellite-derived SWE data for runoff simulation.

  3. MODEL EVALUASI REFLEKTIF KURIKULUM PENDIDIKAN BAHASA INGGRIS DALAM PENGEMBANGAN KARAKTER BANGSA

    Directory of Open Access Journals (Sweden)

    Monika Gultom

    2014-06-01

    Abstract This study aimed to develop a model of reflective curriculum evaluation at the English Education Study Program that portrayed the delivery of the values of national character in the classroom. This development study used mixed approach carried out in five phases:  initial study, defining, designing, demonstrating, and developing.  The constructs of instruments were developed based on expert judgments; the subjects were lecturers and students of English Language Education Study Program in four universities in Yogyakarta Special Territory. The composite reliability coefficient of the instruments was analyzed by SEM program of SmartPLS Version 2.0.M3 and test of fit model by GeSCA. The result of the study concluded: 1 the developed model evaluation was supported by five instruments of evaluation; 2 validity, reliability, and its implementation had been verified through FGD, Delphy techniques, and non-parametric confirmatory factor analysis; 3 the composite reliability coefficient of the five instruments was 0.93, 0.91, 0.95, 0.95, and 0.86; 4 the result of the test of fit model indicated that  model was supported by the data with GFI 0.99 and SRMR 0.06; 5 The guidelines of using the developed model consisted of background, rational, components of assessment, guidelines, and application sample.Keywords: developing model of curriculum evaluation, national character

  4. The Joint Space-Time Statistics Of Macroweather Precipitation, Space-Time Statistical Factorization And Macroweather Models

    Science.gov (United States)

    Lovejoy, S.; de Lima, I. P.

    2015-12-01

    Over the range of time scales from about 10 days to 30-100 years, in addition to the familiar weather and climate regimes, there is an intermediate "macroweather" regime characterized by negative temporal fluctuation exponents: implying that fluctuations tend to cancel each other out, that averages tend to converge. We show theoretically and numerically that macroweather precipitation can be modeled by a stochastic weather-climate model (the Climate Extended Fractionally Integrated Flux, model, CEFIF) first proposed for macroweather temperatures and we show numerically that a four parameter space-time CEFIF model can approximately reproduce eight or so empirical space-time exponents. In spite of this success, CEFIF is theoretically and numerically difficult to manage. We therefore propose a simplified stochastic model in which the temporal behavior is modeled as a fractional Gaussian noise but the spatial behaviour as a multifractal (climate) cascade: a spatial extension of the recently introduced ScaLIng Macroweather Model, SLIMM. Both the CEFIF and this spatial SLIMM model have a property often implicitly assumed by climatologists: that climate statistics can be "homogenized" by normalizing them with the standard deviation of the anomalies. Physically, it means that the spatial macroweather variability corresponds to different climate zones that multiplicatively modulate the local, temporal statistics. This simplified macroweather model provides a framework for macroweather forecasting that exploits the system's long range memory and spatial correlations. We test factorization and the model with the help of three centennial, global scale precipitation products that we analyze jointly in space-time.

  5. The eXtraordinarY Kids Clinic: an interdisciplinary model of care for children and adolescents with sex chromosome aneuploidy

    Directory of Open Access Journals (Sweden)

    Tartaglia N

    2015-07-01

    Full Text Available Nicole Tartaglia,1,2 Susan Howell,1,2 Rebecca Wilson,2 Jennifer Janusz,1,2 Richard Boada,1,2 Sydney Martin,2 Jacqueline B Frazier,2 Michelle Pfeiffer,2 Karen Regan,2 Sarah McSwegin,2 Philip Zeitler1,2 1Department of Pediatrics, University of Colorado School of Medicine, 2Child Development Unit, Children's Hospital Colorado, Aurora, CO, USA Purpose: Individuals with sex chromosome aneuploidies (SCAs are born with an atypical number of X and/or Y chromosomes, and present with a range of medical, developmental, educational, behavioral, and psychological concerns. Rates of SCA diagnoses in infants and children are increasing, and there is a need for specialized interdisciplinary care to address associated risks. The eXtraordinarY Kids Clinic was established to provide comprehensive and experienced care for children and adolescents with SCA, with an interdisciplinary team composed of developmental–behavioral pediatrics, endocrinology, genetic counseling, child psychology, pediatric neuropsychology, speech–language pathology, occupational therapy, nursing, and social work. The clinic model includes an interdisciplinary approach to care, where assessment results by each discipline are integrated to develop unified diagnostic impressions and treatment plans individualized for each patient. Additional objectives of the eXtraordinarY Kids Clinic program include prenatal genetic counseling, research, education, family support, and advocacy. Methods: Satisfaction surveys were distributed to 496 patients, and responses were received from 168 unique patients. Results: Satisfaction with the overall clinic visit was ranked as “very satisfied” in 85%, and as “satisfied” in another 9.8%. Results further demonstrate specific benefits from the clinic experience, the importance of a knowledgeable clinic coordinator, and support the need for similar clinics across the country. Three case examples of the interdisciplinary approach to assessment and

  6. Applying Model Based Systems Engineering to NASA's Space Communications Networks

    Science.gov (United States)

    Bhasin, Kul; Barnes, Patrick; Reinert, Jessica; Golden, Bert

    2013-01-01

    System engineering practices for complex systems and networks now require that requirement, architecture, and concept of operations product development teams, simultaneously harmonize their activities to provide timely, useful and cost-effective products. When dealing with complex systems of systems, traditional systems engineering methodology quickly falls short of achieving project objectives. This approach is encumbered by the use of a number of disparate hardware and software tools, spreadsheets and documents to grasp the concept of the network design and operation. In case of NASA's space communication networks, since the networks are geographically distributed, and so are its subject matter experts, the team is challenged to create a common language and tools to produce its products. Using Model Based Systems Engineering methods and tools allows for a unified representation of the system in a model that enables a highly related level of detail. To date, Program System Engineering (PSE) team has been able to model each network from their top-level operational activities and system functions down to the atomic level through relational modeling decomposition. These models allow for a better understanding of the relationships between NASA's stakeholders, internal organizations, and impacts to all related entities due to integration and sustainment of existing systems. Understanding the existing systems is essential to accurate and detailed study of integration options being considered. In this paper, we identify the challenges the PSE team faced in its quest to unify complex legacy space communications networks and their operational processes. We describe the initial approaches undertaken and the evolution toward model based system engineering applied to produce Space Communication and Navigation (SCaN) PSE products. We will demonstrate the practice of Model Based System Engineering applied to integrating space communication networks and the summary of its

  7. Temporal profile of the effects of intracisternal injection of magnesium sulfate solution on vasodilation of spastic cerebral arteries in the canine SAH model.

    Science.gov (United States)

    Mori, Kentaro; Miyazaki, Masahiro; Hara, Yasukazu; Aiko, Yasuhisa; Yamamoto, Takuji; Nakao, Yasuaki; Esaki, Takanori

    2011-01-01

    the temporal profiles of the effects of intracisternal injection of magnesium sulfate (MgSO(4)) on vasodilation and cerebrospinal fluid (CSF) magnesium ion (Mg(2+)) concentration were investigated in the canine subarachnoid hemorrhage (SAH) model. cerebral vasospasm was induced using the two-hemorrhage model in seven female beagles. On day 7, 0.5 ml/kg of 15 mmol/l MgSO(4) in Ringer solution was injected into the cerebellomedullary cistern. Angiography was performed on day 1 (before SAH), and before and 1, 3, and 6 h after the intracisternal injection on day 7. CSF Mg(2+) was measured at the same time. the diameters of the basilar artery (BA), vertebral artery (VA), and superior cerebellar artery (SCA) before the intracisternal injection on day 7 were 0.59 ± 0.15, 0.41 ± 0.17, and 0.35 ± 0.17 mm, respectively, and were significantly decreased (p < 0.01) compared with the baseline diameters on day 1. The BA diameters at 1 h (0.74 ± 0.16 mm) and 3 h (0.73 ± 0.13 mm), the VA diameter at 1 h (0.64 ± 0.14 mm), and the SCA diameter at 3 h (0.54 ± 0.08 mm) after the injection were significantly increased (p < 0.05). The CSF Mg(2+) concentration was significantly increased (p < 0.01) at 1 h (3.59 ± 0.76 mEq/l) and 3 h (2.00 ± 0.31 mEq/l) after the injection compared with the baseline value (1.35 ± 0.23 mEq/l). the reversible effect of intracisternal MgSO(4) solution injection on the spastic artery depends on maintenance of the optimal CSF Mg(2+) concentration.

  8. Effect of intrathecal magnesium sulfate solution injection via a microcatheter in the cisterna magna on cerebral vasospasm in the canine subarachnoid haemorrhage model.

    Science.gov (United States)

    Mori, Kentaro; Yamamoto, Takuji; Miyazaki, Masahiro; Hara, Yasukazu; Aiko, Yasuhisa; Koike, Nobuhiro; Sakamoto, Shinsuke; Nakao, Yasuaki; Esaki, Takanori

    2012-02-01

    To evaluate intracisternal injection of magnesium sulfate (MgSO(4)) solution via a lumbar catheter for the treatment of cerebral vasospasm in the canine subarachnoid haemorrhage (SAH) model. SAH was induced in 7 beagle dogs using the dual haemorrhage model. Vertebral angiography was repeated on Day 1 (before SAH), and on Day 7 (during cerebral vasospasm) before and 1.5 hours after injection of 0.5 mL/kg of 15 mmol/L MgSO(4) in Ringer solution via the tip of a microcatheter placed in the cisterna magna from the lumbar spine. After injection of MgSO(4) solution, the cerebrospinal fluid magnesium ion concentration significantly increased to 3.89 ± 0.97 mEq/L (P < 0.01) from the baseline value (1.49 ± 0.07 mEq/L). The arterial diameters of the basilar artery (BA), vertebral artery (VA), and superior cerebral artery (SCA) on Day 1 were 1.26 ± 0.19 mm, 1.10 ± 0.13 mm, and 0.74 ± 0.21 mm, respectively. On Day 7 before injection, the arterial diameters of the BA, VA, and SCA significantly decreased to 0.75 ± 0.27 mm, 0.74 ± 0.25 mm, and 0.36 ± 0.21 mm, respectively (P < 0.01), due to vasospasm, and were significantly increased to 0.91 ± 0.27 mm (P < 0.01), 0.91 ± 0.31 mm (P < 0.05), and 0.54 ± 0.14 mm (P < 0.01), respectively, after intracisternal injection of MgSO(4) solution. Intracisternal MgSO(4) therapy using a microcatheter from the lumbar spine may be effective against vasospasm in the clinical setting of endovascular treatment of ruptured aneurysm.

  9. Spheroid-plug model as a tool to study tumor development, angiogenesis, and heterogeneity in vivo.

    Science.gov (United States)

    Szade, Krzysztof; Zukowska, Monika; Szade, Agata; Collet, Guillaume; Kloska, Damian; Kieda, Claudine; Jozkowicz, Alicja; Dulak, Jozef

    2016-02-01

    Subcutaneous injection of the tumor cell suspension is a simple and commonly used tool for studying tumor development in vivo. However, subcutaneous models poorly resemble tumor complexity due to the fast growth not reflecting the natural course. Here, we describe an application of the new spheroid-plug model to combine the simplicity of subcutaneous injection with improved resemblance to natural tumor progression. Spheroid-plug model relies on in vitro formation of tumor spheroids, followed by injection of single tumor spheroid subcutaneously in Matrigel matrix. In spheroid-plug model, tumors grow slower in comparison to tumors formed by injection of cell suspension as assessed by 3D ultrasonography (USG) and in vivo bioluminescence measurements. The slower tumor growth rate in spheroid-plug model is accompanied by reduced necrosis. The spheroid-plug model ensures increased and more stable vascularization of tumor than classical subcutaneous tumor model as demonstrated by 3D USG Power Doppler examination. Flow cytometry analysis showed that tumors formed from spheroids have enhanced infiltration of endothelial cells as well as hematopoietic and progenitor cells with stem cell phenotype (c-Kit(+) and Sca-1(+)). They also contain more tumor cells expressing cancer stem cell marker CXCR4. Here, we show that spheroid-plug model allows investigating efficiency of anticancer drugs. Treatment of spheroid-plug tumors with known antiangiogenic agent axitinib decreased their size and viability. The antiangiogenic activity of axitinib was higher in spheroid-plug model than in classical model. Our results indicate that spheroid-plug model imitates natural tumor growth and can become a valuable tool for cancer research.

  10. Bokolo v S 2014 (1) sacr 66 (sca): The practicality of challenging ...

    African Journals Online (AJOL)

    Drawing from the Supreme Court of Appeal decision in Bokolo v S(Bokolo case), this case note discusses how DNA evidence can be placed in its proper forensic context. The article sets out the ideal role of expert witnesses, the role of opposing or neutral experts, and the active role of judicial officers in evaluating DNA ...

  11. Immunomagnetic Separation of Fat Depot-Specific Sca1high Adipose-Derived Stem Cells (Ascs)

    OpenAIRE

    Barnes, Richard H.; Chun, Tae-Hwa

    2016-01-01

    The isolation of adipose-derived stem cells (ASCs) is an important method in the field of adipose tissue biology, adipogenesis, and extracellular matrix (ECM) remodeling. In vivo, ECM-rich environment consisting of fibrillar collagens provides a structural support to adipose tissues during the progression and regression of obesity. Physiological ECM remodeling mediated by matrix metalloproteinases (MMPs) plays a major role in regulating adipose tissue size and function1, 2. The loss of physio...

  12. Exploration of CAG triplet repeat in nontranslated region of SCA12 ...

    Indian Academy of Sciences (India)

    ... Kingdom of Saudi Arabia; Department of Genetics and Molecular Medicine, Kamineni Hospitals, LB Nagar, Hyderabad 500 068, India; Department of Genetic Medicine, Faculty of Medicine, Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders, King Abdul-Aziz University, Jeddah 21589, Kingdom ...

  13. Infantile onset spinocerebellar ataxia 2 (SCA2): a clinical report with review of previous cases.

    Science.gov (United States)

    Singh, Ankur; Faruq, Mohammed; Mukerji, Mitali; Dwivedi, Manish Kumar; Pruthi, Sumit; Kapoor, Seema

    2014-01-01

    Autosomal dominant cerebellar ataxia type I is a heterogeneous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.

  14. ScaMo: Realisation of an OO-functional DSL for cross platform mobile applications development

    Science.gov (United States)

    Macos, Dragan; Solymosi, Andreas

    2013-10-01

    The software market is dynamically changing: the Internet is going mobile, the software applications are shifting from the desktop hardware onto the mobile devices. The largest markets are the mobile applications for iOS, Android and Windows Phone and for the purpose the typical programming languages include Objective-C, Java and C ♯. The realization of the native applications implies the integration of the developed software into the environments of mentioned mobile operating systems to enable the access to different hardware components of the devices: GPS module, display, GSM module, etc. This paper deals with the definition and possible implementation of an environment for the automatic application generation for multiple mobile platforms. It is based on a DSL for mobile application development, which includes the programming language Scala and a DSL defined in Scala. As part of a multi-stage cross-compiling algorithm, this language is translated into the language of the affected mobile platform. The advantage of our method lies in the expressiveness of the defined language and the transparent source code translation between different languages, which implies, for example, the advantages of debugging and development of the generated code.

  15. Study on the Dynamic Biological Characteristics of Sca-1+ Hematopoietic Stem and Progenitor Cell Senescence

    Directory of Open Access Journals (Sweden)

    Shan Geng

    2015-01-01

    Full Text Available The researches in the dynamic changes of the progress of HSCs aging are very limited and necessary. In this study, male C57BL/6 mice were divided into 5 groups by age. We found that the superoxide damage of HSPCs started to increase from the middle age (6 months old, with notably reduced antioxidation ability. In accordance with that, the senescence of HSPCs also started from the middle age, since the self-renewal and differentiation ability remarkably decreased, and senescence-associated markers SA-β-GAL increased in the 6-month-old and the older groups. Interestingly, the telomere length and telomerase activity increased to a certain degree in the 6-month-old group. It suggested an intrinsic spontaneous ability of HSPCs against aging. It may provide a theoretical and experimental foundation for better understanding the senescence progress of HSPCs. And the dynamic biological characteristics of HSPCs senescence may also contribute to the clinical optimal time for antiaging drug intervention.

  16. S v Litako 2014 SACR 431 (SCA): a clarification on extra curial ...

    African Journals Online (AJOL)

    Potchefstroom Electronic Law Journal/Potchefstroomse Elektroniese Regsblad. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 18, No 2 (2015) >. Log in or Register to get access to full text downloads.

  17. Performing DISCO-SCA to search for distinctive and common information in linked data

    NARCIS (Netherlands)

    Schouteden, Martijn; Van Deun, Katrijn; Wilderjans, Tom F.; Van Mechelen, Iven

    2014-01-01

    Behavioral researchers often obtain information about the same set of entities from different sources. A main challenge in the analysis of such data is to reveal, on the one hand, the mechanisms underlying all of the data blocks under study and, on the other hand, the mechanisms underlying a single

  18. DISCO-SCA and Properly Applied GSVD as Swinging Methods to Find Common and Distinctive Processes

    National Research Council Canada - National Science Library

    Van Deun, Katrijn; Van Mechelen, Iven; Thorrez, Lieven; Schouteden, Martijn; De Moor, Bart; van der Werf, Mariet J; De Lathauwer, Lieven; Smilde, Age K; Kiers, Henk A. L

    2012-01-01

    .... A major challenge is to find the important biological processes underlying the data and to disentangle therein processes common to all data sources and processes distinctive for a specific source...

  19. DISCO-SCA and properly applied GSVD as swinging methods to find common and distinctive processes

    National Research Council Canada - National Science Library

    van Deun, K; van Mechelen, I; Thorrez, L; Schouteden, M; de Moor, B; van der Werf, M.J; de Lathauwer, L; Smilde, A.K; Kiers, H.A.L

    2012-01-01

    .... A major challenge is to find the important biological processes underlying the data and to disentangle therein processes common to all data sources and processes distinctive for a specific source...

  20. Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

    2015-03-01

    The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  1. The joint space-time statistics of macroweather precipitation, space-time statistical factorization and macroweather models

    Energy Technology Data Exchange (ETDEWEB)

    Lovejoy, S., E-mail: lovejoy@physics.mcgill.ca [Physics Department, McGill University, Montreal, Quebec H3A 2T8 (Canada); Lima, M. I. P. de [Institute of Marine Research (IMAR) and Marine and Environmental Sciences Centre (MARE), Coimbra (Portugal); Department of Civil Engineering, University of Coimbra, 3030-788 Coimbra (Portugal)

    2015-07-15

    Over the range of time scales from about 10 days to 30–100 years, in addition to the familiar weather and climate regimes, there is an intermediate “macroweather” regime characterized by negative temporal fluctuation exponents: implying that fluctuations tend to cancel each other out so that averages tend to converge. We show theoretically and numerically that macroweather precipitation can be modeled by a stochastic weather-climate model (the Climate Extended Fractionally Integrated Flux, model, CEFIF) first proposed for macroweather temperatures and we show numerically that a four parameter space-time CEFIF model can approximately reproduce eight or so empirical space-time exponents. In spite of this success, CEFIF is theoretically and numerically difficult to manage. We therefore propose a simplified stochastic model in which the temporal behavior is modeled as a fractional Gaussian noise but the spatial behaviour as a multifractal (climate) cascade: a spatial extension of the recently introduced ScaLIng Macroweather Model, SLIMM. Both the CEFIF and this spatial SLIMM model have a property often implicitly assumed by climatologists that climate statistics can be “homogenized” by normalizing them with the standard deviation of the anomalies. Physically, it means that the spatial macroweather variability corresponds to different climate zones that multiplicatively modulate the local, temporal statistics. This simplified macroweather model provides a framework for macroweather forecasting that exploits the system's long range memory and spatial correlations; for it, the forecasting problem has been solved. We test this factorization property and the model with the help of three centennial, global scale precipitation products that we analyze jointly in space and in time.

  2. Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050: Modelling Based on Demographics, Excess Mortality, and Interventions

    Science.gov (United States)

    Piel, Frédéric B.; Hay, Simon I.; Gupta, Sunetra; Weatherall, David J.; Williams, Thomas N.

    2013-01-01

    Background The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions. Methods and Findings First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400–398,800) in 2010 to 404,200 (CI: 242,500–657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900–106,100]; 2050: 140,800 [CI: 95,500–200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600–48,800]; 2050: 44,700 [CI: 27,100–70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700–59,100]; 2050: 33,900 [CI: 15,900–64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5

  3. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions.

    Science.gov (United States)

    Piel, Frédéric B; Hay, Simon I; Gupta, Sunetra; Weatherall, David J; Williams, Thomas N

    2013-01-01

    The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions. First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns with

  4. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions.

    Directory of Open Access Journals (Sweden)

    Frédéric B Piel

    Full Text Available The global burden of sickle cell anaemia (SCA is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800 in 2010 to 404,200 (CI: 242,500-657,600 in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600] and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500] will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]. The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3

  5. Dystonia and ataxia progression in spinocerebellar ataxias.

    Science.gov (United States)

    Kuo, Pei-Hsin; Gan, Shi-Rui; Wang, Jie; Lo, Raymond Y; Figueroa, Karla P; Tomishon, Darya; Pulst, Stefan M; Perlman, Susan; Wilmot, George; Gomez, Christopher M; Schmahmann, Jeremy D; Paulson, Henry; Shakkottai, Vikram G; Ying, Sarah H; Zesiewicz, Theresa; Bushara, Khalaf; Geschwind, Michael D; Xia, Guangbin; Subramony, S H; Ashizawa, Tetsuo; Kuo, Sheng-Han

    2017-10-23

    Dystonia is a common feature in spinocerebellar ataxias (SCAs). Whether the presence of dystonia is associated with different rate of ataxia progression is not known. To study clinical characteristics and ataxia progression in SCAs with and without dystonia. We studied 334 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and compared the clinical characteristics of SCAs with and without dystonia. We repeatedly measured ataxia progression by the Scale for Assessment and Rating of Ataxia every 6 months for 2 years. Regression models were employed to study the association between dystonia and ataxia progression after adjusting for age, sex and pathological CAG repeats. We used logistic regression to analyze the impact of different repeat expansion genes on dystonia in SCAs. Dystonia was most commonly observed in SCA3, followed by SCA2, SCA1, and SCA6. Dystonia was associated with longer CAG repeats in SCA3. The CAG repeat number in TBP normal alleles appeared to modify the presence of dystonia in SCA1. The presence of dystonia was associated with higher SARA scores in SCA1, 2, and 3. Although relatively rare in SCA6, the presence of dystonia was associated with slower progression of ataxia. The presence of dystonia is associated with greater severity of ataxia in SCA1, 2, and 3, but predictive of a slower progression in SCA6. Complex genetic interactions among repeat expansion genes can lead to diverse clinical symptoms and progression in SCAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Photo-Realistic 3D Modelling of Sculptures on Open-Air Museums

    Directory of Open Access Journals (Sweden)

    Francesca Duca

    2011-12-01

    Full Text Available Laser scanning is a high-end technology with possibilities far ahead the well-known civil engineering and industrial applications. The actual geomatic technologies and methodologies for cultural heritage documentation allow the generation of very realistic 3D results used for many scopes like archaeological documentation, digital conservation, 3D repositories, etc. The fast acquisition times of large number of point clouds in 3D opens up the world of capabilities to document and keep alive cultural heritage, moving forward the generation of virtual animated replicas of great value and smooth multimedia dissemination. This paper presents the use of a terrestrial laser sca nning (TLS as a valuable tool for 3D documentation of large outdoor cultural heritage sculptures such as two of the existing ones inside the “Campus de Vera” of the UPV: “Defensas I” and “Mentoring”. The processing of the TLS data is discussed in detail in order to create photo-realistic digital models. Data acquisition is conducted with a time-of-flight scanner, characterized by its high accuracy, small beam, and ultra-fine scanning. Data processing is performed using Leica Geosystems Cyclone Software for the data registration and 3DReshaper Software for modelling and texturing.  High-resolution images after calibration and orientation of an off-the-shelf digital camera are draped onto the models to achieve right appearance in colour and texture. A discussion on the differences found out when modelling sculptures with different deviation errors will be presented. Processing steps such as normal smoothing and vertices recalculation are found appropriate to achieve continuous meshes around the objects.

  7. Models and Modeling.

    Science.gov (United States)

    Lesh, Richard; Carmona, Guadalupe; Post, Thomas

    In this workshop, we will continue to reflect on a models and modeling perspective to understand how students and teachers learn and reason about real life situations encountered in a mathematics and science classroom. We will discuss the idea of a model as a conceptual system that is expressed by using external representational media, and that is…

  8. Moving horizon estimation for assimilating H-SAF remote sensing data into the HBV hydrological model

    Science.gov (United States)

    Montero, Rodolfo Alvarado; Schwanenberg, Dirk; Krahe, Peter; Lisniak, Dmytro; Sensoy, Aynur; Sorman, A. Arda; Akkol, Bulut

    2016-06-01

    Remote sensing information has been extensively developed over the past few years including spatially distributed data for hydrological applications at high resolution. The implementation of these products in operational flow forecasting systems is still an active field of research, wherein data assimilation plays a vital role on the improvement of initial conditions of streamflow forecasts. We present a novel implementation of a variational method based on Moving Horizon Estimation (MHE), in application to the conceptual rainfall-runoff model HBV, to simultaneously assimilate remotely sensed snow covered area (SCA), snow water equivalent (SWE), soil moisture (SM) and in situ measurements of streamflow data using large assimilation windows of up to one year. This innovative application of the MHE approach allows to simultaneously update precipitation, temperature, soil moisture as well as upper and lower zones water storages of the conceptual model, within the assimilation window, without an explicit formulation of error covariance matrixes and it enables a highly flexible formulation of distance metrics for the agreement of simulated and observed variables. The framework is tested in two data-dense sites in Germany and one data-sparse environment in Turkey. Results show a potential improvement of the lead time performance of streamflow forecasts by using perfect time series of state variables generated by the simulation of the conceptual rainfall-runoff model itself. The framework is also tested using new operational data products from the Satellite Application Facility on Support to Operational Hydrology and Water Management (H-SAF) of EUMETSAT. This study is the first application of H-SAF products to hydrological forecasting systems and it verifies their added value. Results from assimilating H-SAF observations lead to a slight reduction of the streamflow forecast skill in all three cases compared to the assimilation of streamflow data only. On the other hand

  9. Evaluating the Influence of Motor Control on Selective Attention through a Stochastic Model: The Paradigm of Motor Control Dysfunction in Cerebellar Patient

    Directory of Open Access Journals (Sweden)

    Giacomo Veneri

    2014-01-01

    Full Text Available Attention allows us to selectively process the vast amount of information with which we are confronted, prioritizing some aspects of information and ignoring others by focusing on a certain location or aspect of the visual scene. Selective attention is guided by two cognitive mechanisms: saliency of the image (bottom up and endogenous mechanisms (top down. These two mechanisms interact to direct attention and plan eye movements; then, the movement profile is sent to the motor system, which must constantly update the command needed to produce the desired eye movement. A new approach is described here to study how the eye motor control could influence this selection mechanism in clinical behavior: two groups of patients (SCA2 and late onset cerebellar ataxia LOCA with well-known problems of motor control were studied; patients performed a cognitively demanding task; the results were compared to a stochastic model based on Monte Carlo simulations and a group of healthy subjects. The analytical procedure evaluated some energy functions for understanding the process. The implemented model suggested that patients performed an optimal visual search, reducing intrinsic noise sources. Our findings theorize a strict correlation between the “optimal motor system” and the “optimal stimulus encoders.”

  10. Modelling Practice

    DEFF Research Database (Denmark)

    Cameron, Ian; Gani, Rafiqul

    2011-01-01

    requirements; model construction; model solution; model verification; model validation and finally model deployment and maintenance. Within the adopted methodology, each step is discussedthrough the consideration of key issues and questions relevant to the modelling activity. Practical advice, based on many...

  11. Research progress of spinocerebellar ataxia type 1

    Directory of Open Access Journals (Sweden)

    Lin-wei ZHANG

    2014-05-01

    Full Text Available Spinocerebellar ataxia type 1 (SCA1 is a kind of autosomal dominant genetic neurodegenerative disorder. To date, the pathogenesis of SCA1 remains unclear. Studies in numerous SCA1 experimental models, including transgenic mice, transgenic drosophila and induced pluripotent stem cells, have shown that phosphorylation of S776 in mutant ataxin-1, molecular chaperones, ubiquitin-proteasome system and down-regulation of several components of RAS-MAPK-MSK1 pathway may involve in the pathogenesis of SCA1. In this review, the clinical and pathological features of SCA1, and the latest advances of pathogenesis, model systems and therapeutic exploration will be briefly summarized. doi: 10.3969/j.issn.1672-6731.2014.05.017

  12. Models and role models

    NARCIS (Netherlands)

    ten Cate, J.M.

    2015-01-01

    Developing experimental models to understand dental caries has been the theme in our research group. Our first, the pH-cycling model, was developed to investigate the chemical reactions in enamel or dentine, which lead to dental caries. It aimed to leverage our understanding of the fluoride mode of

  13. Model(ing) Law

    DEFF Research Database (Denmark)

    Carlson, Kerstin

    The International Criminal Tribunal for the former Yugoslavia (ICTY) was the first and most celebrated of a wave of international criminal tribunals (ICTs) built in the 1990s designed to advance liberalism through international criminal law. Model(ing) Justice examines the case law of the ICTY...

  14. Modelling business models

    NARCIS (Netherlands)

    Simonse, W.L.

    2014-01-01

    Business model design does not always produce a “design” or “model” as the expected result. However, when designers are involved, a visual model or artifact is produced. To assist strategic managers in thinking about how they can act, the designers’ challenge is to combine both strategy and design

  15. Parabolic Trough Collector Cost Update for the System Advisor Model (SAM)

    Energy Technology Data Exchange (ETDEWEB)

    Kurup, Parthiv [National Renewable Energy Lab. (NREL), Golden, CO (United States); Turchi, Craig S. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-11-01

    This report updates the baseline cost for parabolic trough solar fields in the United States within NREL's System Advisor Model (SAM). SAM, available at no cost at https://sam.nrel.gov/, is a performance and financial model designed to facilitate decision making for people involved in the renewable energy industry. SAM is the primary tool used by NREL and the U.S. Department of Energy (DOE) for estimating the performance and cost of concentrating solar power (CSP) technologies and projects. The study performed a bottom-up build and cost estimate for two state-of-the-art parabolic trough designs -- the SkyTrough and the Ultimate Trough. The SkyTrough analysis estimated the potential installed cost for a solar field of 1500 SCAs as $170/m2 +/- $6/m2. The investigation found that SkyTrough installed costs were sensitive to factors such as raw aluminum alloy cost and production volume. For example, in the case of the SkyTrough, the installed cost would rise to nearly $210/m2 if the aluminum alloy cost was $1.70/lb instead of $1.03/lb. Accordingly, one must be aware of fluctuations in the relevant commodities markets to track system cost over time. The estimated installed cost for the Ultimate Trough was only slightly higher at $178/m2, which includes an assembly facility of $11.6 million amortized over the required production volume. Considering the size and overall cost of a 700 SCA Ultimate Trough solar field, two parallel production lines in a fully covered assembly facility, each with the specific torque box, module and mirror jigs, would be justified for a full CSP plant.

  16. Investigation of lightning flash morphologies along the entire supercell life cycle using a numerical 3D cloud resolving model(CRM).

    Science.gov (United States)

    Molinié, G.; Escobar, J.; Gazin, D.

    2008-12-01

    A stochastic lightning flash scheme has been implemented in line in a meso-sca le CRM. It is fully parallelized and vectorized. In this model, a lightning flash is schematized as two single conducting channels (single tracks) propagating in opposite directions from the lightning ignition point. Branch patterns propagate from the single channels. On the base of scale similarities between discharges in dielectrics at centimeter scales and lightning flashes, the stochastic scheme has been designed to compute branch trajec tories. Physical considerations and branch fractal dimensions compel branch trajectories. The charge neutralization operates along the single tracks and branches to threshold the cloud electrical charge. First, an assessment of the scheme will be presented in simple 2D configurations. Second, we will describe comprehensive 3D-thundercloud life-cycle simulations including cloud electrification and lightning discharges. Lightning flash patterns are analyzed through statistics of their effective fractal dimension. It is shown that paradoxically, lightning flashes with quasi-plane branch propagation (fractal dimension close to 2) lead to more steady electrical behavior than those completely filling volumes (fractal dimension close to 3).

  17. Modelling SDL, Modelling Languages

    Directory of Open Access Journals (Sweden)

    Michael Piefel

    2007-02-01

    Full Text Available Today's software systems are too complex to implement them and model them using only one language. As a result, modern software engineering uses different languages for different levels of abstraction and different system aspects. Thus to handle an increasing number of related or integrated languages is the most challenging task in the development of tools. We use object oriented metamodelling to describe languages. Object orientation allows us to derive abstract reusable concept definitions (concept classes from existing languages. This language definition technique concentrates on semantic abstractions rather than syntactical peculiarities. We present a set of common concept classes that describe structure, behaviour, and data aspects of high-level modelling languages. Our models contain syntax modelling using the OMG MOF as well as static semantic constraints written in OMG OCL. We derive metamodels for subsets of SDL and UML from these common concepts, and we show for parts of these languages that they can be modelled and related to each other through the same abstract concepts.

  18. Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

    Directory of Open Access Journals (Sweden)

    Xinyi Mu

    2017-01-01

    Full Text Available Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP, a major active ingredient in dong quai (Chinese Angelica Sinensis, on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1 ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS, 8-OHdG, and 4-HNE were declined, (2 ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3 ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

  19. Partial Characterization of the Sox2+ Cell Population in an Adult Murine Model of Digit Amputation

    Science.gov (United States)

    Agrawal, Vineet; Siu, Bernard F.; Chao, Hsu; Hirschi, Karen K.; Raborn, Eric; Johnson, Scott A.; Tottey, Stephen; Hurley, Katherine B.; Medberry, Chris J.

    2012-01-01

    Tissue regeneration in response to injury in adult mammals is generally limited to select tissues. Nonmammalian species such as newts and axolotls undergo regeneration of complex tissues such as limbs and digits via recruitment and accumulation of local and circulating multipotent progenitors preprogrammed to recapitulate the missing tissue. Directed recruitment and activation of progenitor cells at a site of injury in adult mammals may alter the default wound-healing response from scar tissue toward regeneration. Bioactive molecules derived from proteolytic degradation of extracellular matrix (ECM) proteins have been shown to recruit a variety of progenitor cells in vitro and in vivo to the site of injury. The present study further characterized the population of cells accumulating at the site of injury after treatment with ECM degradation products in a well-established model of murine digit amputation. After a mid-second phalanx digit amputation in 6–8-week-old adult mice, treatment with ECM degradation products resulted in the accumulation of a heterogeneous population of cells, a subset of which expressed the transcription factor Sox2, a marker of pluripotent and adult progenitor cells. Sox2+ cells were localized lateral to the amputated P2 bone and coexpressed progenitor cell markers CD90 and Sca1. Transgenic Sox2 eGFP/+ and bone marrow chimeric mice showed that the bone marrow and blood circulation did not contribute to the Sox2+ cell population. The present study showed that, in addition to circulating progenitor cells, resident tissue-derived cells also populate at the site of injury after treatment with ECM degradation products. Although future work is necessary to determine the contribution of Sox2+ cells to functional tissue at the site of injury, recruitment and/or activation of local tissue-derived cells may be a viable approach to tissue engineering of more complex tissues in adult mammals. PMID:22530556

  20. Model-model Evaluasi Pendidikan

    OpenAIRE

    Qomari, Rohmad

    2008-01-01

    On learning literature, there many kind of learning model design, for example model developed by Winarno Surakhmad, Winkel, Hisyam Zaini et al., Briggs and Wager, Gerlach and Ely, and Kemp. Those models design have component and pattern that different each other, from model that have dominant quantitative measure like measurement model and model that using qualitative approach as illuminative model. By studying many models and broaden view not only to one model approach, and even combine (m...

  1. Actant Models

    DEFF Research Database (Denmark)

    Poulsen, Helle

    1996-01-01

    This paper presents a functional modelling method called Actant Modelling rooted in linguistics and semiotics. Actant modelling can be integrated with Multilevel Flow Modelling (MFM) in order to give an interpretation of actants.......This paper presents a functional modelling method called Actant Modelling rooted in linguistics and semiotics. Actant modelling can be integrated with Multilevel Flow Modelling (MFM) in order to give an interpretation of actants....

  2. Modelling the models

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    By analysing the production of mesons in the forward region of LHC proton-proton collisions, the LHCf collaboration has provided key information needed to calibrate extremely high-energy cosmic ray models.   Average transverse momentum (pT) as a function of rapidity loss ∆y. Black dots represent LHCf data and the red diamonds represent SPS experiment UA7 results. The predictions of hadronic interaction models are shown by open boxes (sibyll 2.1), open circles (qgsjet II-03) and open triangles (epos 1.99). Among these models, epos 1.99 shows the best overall agreement with the LHCf data. LHCf is dedicated to the measurement of neutral particles emitted at extremely small angles in the very forward region of LHC collisions. Two imaging calorimeters – Arm1 and Arm2 – take data 140 m either side of the ATLAS interaction point. “The physics goal of this type of analysis is to provide data for calibrating the hadron interaction models – the well-known &...

  3. The insulin-like growth factor pathway is altered in Spinocerebellar ataxia type 1 and type 7

    Energy Technology Data Exchange (ETDEWEB)

    Gatchel, Jennifer R.; Watase, Kei; Thaller, Christina; Carson, James P.; Jafar-Nejad, Paymaan; Shaw, Chad A.; Zu, Tao; Orr, Harry T.; Zoghbi, Huda Yahya

    2008-01-29

    Polyglutamine diseases are inherited neurodegenerative disorders caused by expansion of CAG trinucleotide repeats encoding a polyglutamine tract in the disease-causing proteins. There are nine of these disorders each having distinct features but also clinical and pathological similarities. In particular, spinocerebellar ataxia type 1 and 7 (SCA1 and SCA7) patients manifest cerebellar ataxia with corresponding degeneration of Purkinje cells. Given this common phenotype, we asked whether the two disorders share common molecular pathogenic events. To address this question we studied two genetically accurate mouse models of SCA1 and SCA7—Sca1154Q/2Q and Sca7266Q/5Q knock-in mice—that express the glutamine-expanded proteins from the respective endogenous loci. We found common transcriptional changes in early symptomatic mice, with downregulation of Insulin-like growth factor binding protein 5 (Igfbp5) representing one of the most robust transcriptional changes that closely correlates with disease state. Interestingly, down-regulation of Igfbp5 occurred in granule neurons through a non-cell autonomous mechanism and was concomitant with activation of the Insulin-like growth factor I (Igf-I) pathway, and, in particular, the Igf-I receptor, expressed in part on Purkinje cells (PC). These data define a possible common pathogenic response in SCA1 and SCA7 and reveal the importance of neuron-neuron interactions in SCA1 and SCA7 pathogenesis. The sensitivity of Igfbp5 levels to disease state could render it and other components of its effector pathway useful as biomarkers in this class of diseases.

  4. Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

    Directory of Open Access Journals (Sweden)

    C.M. Lopes-Ramos

    Full Text Available Machado-Joseph disease (MJD or spinocerebellar ataxia type 3 (SCA3 is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3 protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84. In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

  5. Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease.

    Science.gov (United States)

    Lopes-Ramos, C M; Pereira, T C; Dogini, D B; Gilioli, R; Lopes-Cendes, I

    2016-11-21

    Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

  6. SCA resistant Parallel Explicit Formula for Addition and Doubling of Divisors in the Jacobian of Hyperelliptic Curves of Genus 2

    DEFF Research Database (Denmark)

    Lange, Tanja; Mishra, Pradeep Kumar

    2005-01-01

    Hyperelliptic curve cryptosystems (HECC) can be implemented on a variety of computing devices, starting from smart cards to high end workstations. Side-channel attacks are one of the most potential threats against low genus HECC. Thus efficient algorithms resistant against side channel attacks...

  7. MORA DEBITORIS AND THE PRINCIPLE OF STRICT LIABILITY: SCOIN TRADING (PTY LTD V BERNSTEIN 2011 2 SA 118 (SCA

    Directory of Open Access Journals (Sweden)

    SJ Cornelius

    2012-12-01

    Full Text Available Parties generally enter into contractual relations with the sincere intention to fulfil all the obligations created in terms of their contract. However, for various reasons, parties sometimes do not comply with the terms of their contract. Where a party fails to perform at the agreed date and time or after receiving a demand from the creditor, the debtor commits breach of contract in the form of mora debitoris. The question then arises whether or not a debtor would also commit breach in the form of mora debitoris if the delay in performance cannot be attributed to wilful disregard of the contract or a negligent failure to perform on time. This was the question which the court had to determine in Scoin Trading (Pty Ltd v Bernstein.

  8. Evidence of linkage disequilibrium between schizophrenia and the SCA1 CAG repeat on chromosome 6p23

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.; Sun, Cui-E; Diehl, S.R. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1996-09-01

    Schizophrenia and the closely related phenotype schizoaffective disorder are severe mental illnesses that affect >1.0% of the population. The major role that genetic factors contribute to disease susceptibility is very well established. Schizophrenia appears to be a highly complex and heterogeneous disorder, however, and gene-mapping efforts also face challenges in assigning diagnoses and in delineating the disease`s phenotypic boundary. Several recently reported studies indicate that a schizophrenia-susceptibility gene may reside on the distal short arm of chromosome 6. Wang et al. reported a strong suggestion of linkage to chromosome 6pter-p22, using a resource based on 186 Irish families that was developed by K. S, Kendler, D. Walsh and colleagues, and one of us (S.R.D.), as described elsewhere. In that study, locus D6S260 gave the highest pairwise LOD score, 3.5, allowing for locus heterogeneity. Analysis with D6S260 and the distal locus F13A1 yielded a multipoint LOD score of 3.9, which maximized by allowing for locus heterogeneity and assuming that 50% of families are linked to this region. Nonparametric affected-pedigree-member analyses also supported this finding. Several other groups have recently reported additional evidence suggesting linkage to this region, both in an expanded collection of Irish families and in families from a variety of other geographic locations. However, none of these studies succeed in narrowing the location of the putative disease gene beyond the {approximately}30-cM region first identified by Wang et al. 44 refs., 1 fig., 1 tab.

  9. Advances in SCA and RF-DNA Fingerprinting Through Enhanced Linear Regression Attacks and Application of Random Forest Classifiers

    Science.gov (United States)

    2014-09-18

    when 3 or more images were used for classification. All three easily outperform the Naive Bayes Maximum Likelihood method. In [85], the Random Forest is...Maximum Likelihood (MDA/ML) . . . . . . . . . . . . . . . . . . . . . . . . 22 2.5.1.2 Naive Bayes . . . . . . . . . . . . . . . . . . . . . . . . 24...probabilities [59], log-likelihood is used here. Given a known distribution, ML provides optimal classification performance [125]. 2.5.1.2 Naive Bayes If N

  10. Two Distally Located Right SCA Aneurysms: Endovascular Treatment by Parent Artery Occlusion with GDC Coils and N-BCA Injection

    Science.gov (United States)

    Szajner, M.; Obszaska, K.; Nestorowicz, A.; Szczerbo-Trojanowska, M.

    2003-01-01

    Summary Peripheral aneurysms of the superior cerebellar artery are considered difficult to treat surgically and endovascularly because of their inaccessibility. Parent artery occlusion is therefore frequently the preferred method. Embolic materials previously reported in this situation are either GDC coils or a polymerizing agent (n-BCA). We report a patient with two distally located, wide-neck aneurysms of the right superior cerebellar artery who presented with hemorrhage and was treated by endovascular embolization of the parent artery using a combination of GDC coils and n-BCA. PMID:20591270

  11. DISCO-SCA and Properly Applied GSVD as Swinging Methods to Find Common and Distinctive Processes: e37840

    National Research Council Canada - National Science Library

    Katrijn Van Deun; Iven Van Mechelen; Lieven Thorrez; Martijn Schouteden; Bart De Moor; J van der Werf; Lieven De Lathauwer; Age K Smilde; Henk A L Kiers

    2012-01-01

    .... A major challenge is to find the important biological processes underlying the data and to disentangle therein processes common to all data sources and processes distinctive for a specific source...

  12. Increased adhesive and inflammatory properties in blood outgrowth endothelial cells from sickle cell anemia patients.

    Science.gov (United States)

    Sakamoto, Tatiana Mary; Lanaro, Carolina; Ozelo, Margareth Castro; Garrido, Vanessa Tonin; Olalla-Saad, Sara Teresinha; Conran, Nicola; Costa, Fernando Ferreira

    2013-11-01

    The endothelium plays an important role in sickle cell anemia (SCA) pathophysiology, interacting with red cells, leukocytes and platelets during the vaso-occlusive process and undergoing activation and dysfunction as a result of intravascular hemolysis and chronic inflammation. Blood outgrowth endothelial cells (BOECs) can be isolated from adult peripheral blood and have been used in diverse studies, since they have a high proliferative capacity and a stable phenotype during in vitro culture. This study aimed to establish BOEC cultures for use as an in vitro study model for endothelial function in sickle cell anemia. Once established, BOECs from steady-state SCA individuals (SCA BOECs) were characterized for their adhesive and inflammatory properties, in comparison to BOECs from healthy control individuals (CON BOECs). Cell adhesion assays demonstrated that control individual red cells adhered significantly more to SCA BOEC than to CON BOEC. Despite these increased adhesive properties, SCA BOECs did not demonstrate significant differences in their expression of major endothelial adhesion molecules, compared to CON BOECs. SCA BOECs were also found to be pro-inflammatory, producing a significantly higher quantity of the cytokine, IL-8, than CON BOECs. From the results obtained, we suggest that BOEC may be a good model for the in vitro study of SCA. Data indicate that endothelial cells of sickle cell anemia patients may have abnormal inflammatory and adhesive properties even outside of the chronic inflammatory and vaso-occlusive environment of patients. © 2013.

  13. STRUCTURAL MODELLING

    Directory of Open Access Journals (Sweden)

    Tea Ya. Danelyan

    2014-01-01

    Full Text Available The article states the general principles of structural modeling in aspect of the theory of systems and gives the interrelation with other types of modeling to adjust them to the main directions of modeling. Mathematical methods of structural modeling, in particular method of expert evaluations are considered.

  14. Constitutive Models

    DEFF Research Database (Denmark)

    Sales-Cruz, Mauricio; Piccolo, Chiara; Heitzig, Martina

    2011-01-01

    This chapter presents various types of constitutive models and their applications. There are 3 aspects dealt with in this chapter, namely: creation and solution of property models, the application of parameter estimation and finally application examples of constitutive models. A systematic...... procedure is introduced for the analysis and solution of property models. Models that capture and represent the temperature dependent behaviour of physical properties are introduced, as well as equation of state models (EOS) such as the SRK EOS. Modelling of liquid phase activity coefficients are also...... covered, illustrating several models such as the Wilson equation and NRTL equation, along with their solution strategies. A section shows how to use experimental data to regress the property model parameters using a least squares approach. A full model analysis is applied in each example that discusses...

  15. Model theory

    CERN Document Server

    Chang, CC

    2012-01-01

    Model theory deals with a branch of mathematical logic showing connections between a formal language and its interpretations or models. This is the first and most successful textbook in logical model theory. Extensively updated and corrected in 1990 to accommodate developments in model theoretic methods - including classification theory and nonstandard analysis - the third edition added entirely new sections, exercises, and references. Each chapter introduces an individual method and discusses specific applications. Basic methods of constructing models include constants, elementary chains, Sko

  16. Subcellular preconditioning of stem cells: mito-Cx43 gene targeting is cytoprotective via shift of mitochondrial Bak and Bcl-xL balance.

    Science.gov (United States)

    Lu, Gang; Jiang, Shujia; Ashraf, Muhammad; Haider, Khawaja Husnain

    2012-05-01

    To achieve mitochondria-specific expression of connexin-43 (Cx43) transgene for mitochondrial preconditioning in stem cells to improve their survival post-transplantation during heart cell therapy. Cx43- or GFP-encoding adenoviral vectors with a mitochondrial targeting sequence were constructed for transduction of bone marrow Sca-1(+) cells (>90% transduction efficiency). Double-fluorescence immunostaining for cytochrome-c and Cx43 supported by western blotting confirmed mitochondria-specific Cx43 expression in adenoviral-mito-Cx43-transduced cells ((Cx43)Sca-1(+)). (Cx43)Sca-1(+) showed improved survival under lethal oxygen-glucose deprivation culture conditions. (Cx43)Sca-1(+) showed an increased mitochondrial Bcl-xL:Bak ratio and reduced cytochrome-c release into cytosol with concomitantly abolished caspase-3 activity. An in vivo study was performed such that 2 × 10(6) male (Cx43)Sca-1(+) or (GFP)Sca-1(+) cells were injected into a female rat model of acute myocardial infarction. DMEM-injected rats served as controls. On day 7 post-transplantation, 4.3-fold higher survival of (Cx43)Sca-1(+) cells (p targeted Cx43 expression is a novel approach to improve stem cell survival in the infarcted heart.

  17. Massive CAG repeat expansion and somatic instability in maternally transmitted infantile spinocerebellar ataxia type 7.

    Science.gov (United States)

    Trang, Heather; Stanley, Sabrina Y; Thorner, Paul; Faghfoury, Hannaneh; Schulze, Andreas; Hawkins, Cynthia; Pearson, Christopher E; Yoon, Grace

    2015-02-01

    We report the first case to date of maternally transmitted infantile spinocerebellar ataxia type 7 (SCA7), in which a tract of (CAG)45 expands to lengths as large as (CAG)92-250. A 38-year-old woman with classic SCA7 (and a son, who died at age 3 years) had pronounced cerebellar atrophy and a renal biopsy specimen that showed focal segmental glomerulosclerosis with abnormal podocytes containing cytoplasmic inclusions. Polymerase chain reaction amplification across the SCA7 repeat tract assessed expansion levels in tissues of the affected son. High levels of somatic CAG instability were observed in blood, kidney, and skeletal muscle. This transmitted expansion is considerably larger than previously reported maternal transmission expansions of 5 to 10 gained repeats. We document the first intertissue CAG instability reported to date in patients with SCA7, similar to SCA7 mouse models. Infantile SCA7, which is often paternally transmitted, can rarely arise by maternal transmission, which has implications for diagnosis and counseling among families of patients with SCA7.

  18. Modeling Methods

    Science.gov (United States)

    Healy, Richard W.; Scanlon, Bridget R.

    2010-01-01

    Simulation models are widely used in all types of hydrologic studies, and many of these models can be used to estimate recharge. Models can provide important insight into the functioning of hydrologic systems by identifying factors that influence recharge. The predictive capability of models can be used to evaluate how changes in climate, water use, land use, and other factors may affect recharge rates. Most hydrological simulation models, including watershed models and groundwater-flow models, are based on some form of water-budget equation, so the material in this chapter is closely linked to that in Chapter 2. Empirical models that are not based on a water-budget equation have also been used for estimating recharge; these models generally take the form of simple estimation equations that define annual recharge as a function of precipitation and possibly other climatic data or watershed characteristics.Model complexity varies greatly. Some models are simple accounting models; others attempt to accurately represent the physics of water movement through each compartment of the hydrologic system. Some models provide estimates of recharge explicitly; for example, a model based on the Richards equation can simulate water movement from the soil surface through the unsaturated zone to the water table. Recharge estimates can be obtained indirectly from other models. For example, recharge is a parameter in groundwater-flow models that solve for hydraulic head (i.e. groundwater level). Recharge estimates can be obtained through a model calibration process in which recharge and other model parameter values are adjusted so that simulated water levels agree with measured water levels. The simulation that provides the closest agreement is called the best fit, and the recharge value used in that simulation is the model-generated estimate of recharge.

  19. Physical modeling versus numerical modeling

    NARCIS (Netherlands)

    Blacquière, G.; Veldhuizen, E. van

    2003-01-01

    Despite the widespread use of numerical modeling, there is still room for physical modeling today for many reasons. E.g., physical modeling is based on real wave propagation whereas numerical modeling is based on algorithms which are by necessity simplified and discretized versions of the 'real

  20. Model-model Perencanaan Strategik

    OpenAIRE

    Tatang M Amirin

    2005-01-01

    The process of strategic planning, used to be called as long-term planning, consists of several components, including strategic analysis, setting strategic direction (covering of mission, vision, and values), and action planning. Many writers develop models representing the steps of the strategic planning process, i.e. basic planning model, problem-based planning model, scenario model, and organic or self-organizing model.

  1. Event Modeling

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2001-01-01

    The purpose of this chapter is to discuss conceptual event modeling within a context of information modeling. Traditionally, information modeling has been concerned with the modeling of a universe of discourse in terms of information structures. However, most interesting universes of discourse...... are dynamic and we present a modeling approach that can be used to model such dynamics.We characterize events as both information objects and change agents (Bækgaard 1997). When viewed as information objects events are phenomena that can be observed and described. For example, borrow events in a library can...

  2. Numerical models

    Digital Repository Service at National Institute of Oceanography (India)

    Unnikrishnan, A.S.; Manoj, N.T.

    Various numerical models used to study the dynamics and horizontal distribution of salinity in Mandovi-Zuari estuaries, Goa, India is discussed in this chapter. Earlier, a one-dimensional network model was developed for representing the complex...

  3. Watershed models

    National Research Council Canada - National Science Library

    Singh, V.P; Frevert, D.K

    2006-01-01

    This book spans a variety of modeling areas, outlining 24 models that represent a variety of characteristics, such as physical bases, comprehensiveness, broad-based applicability, and use of modern tools...

  4. An ontology-aware integration of clinical models, terminologies and guidelines: an exploratory study of the Scale for the Assessment and Rating of Ataxia (SARA).

    Science.gov (United States)

    Maarouf, Haitham; Taboada, María; Rodriguez, Hadriana; Arias, Manuel; Sesar, Ángel; Sobrido, María Jesús

    2017-12-06

    Electronic rating scales represent an important resource for standardized data collection. However, the ability to exploit reasoning on rating scale data is still limited. The objective of this work is to facilitate the integration of the semantics required to automatically interpret collections of standardized clinical data. We developed an electronic prototype for the Scale of the Assessment and Rating of Ataxia (SARA), broadly used in neurology. In order to address the modeling challenges of the SARA, we propose to combine the best performances from OpenEHR clinical archetypes, guidelines and ontologies. A scaled-down version of the Human Phenotype Ontology (HPO) was built, extracting the terms that describe the SARA tests from free-text sources. This version of the HPO was then used as backbone to normalize the content of the SARA through clinical archetypes. The knowledge required to exploit reasoning on the SARA data was modeled as separate information-processing units interconnected via the defined archetypes. Each unit used the most appropriate technology to formally represent the required knowledge. Based on this approach, we implemented a prototype named SARA Management System, to be used for both the assessment of cerebellar syndrome and the production of a clinical synopsis. For validation purposes, we used recorded SARA data from 28 anonymous subjects affected by Spinocerebellar Ataxia Type 36 (SCA36). When comparing the performance of our prototype with that of two independent experts, weighted kappa scores ranged from 0.62 to 0.86. The combination of archetypes, phenotype ontologies and electronic information-processing rules can be used to automate the extraction of relevant clinical knowledge from plain scores of rating scales. Our results reveal a substantial degree of agreement between the results achieved by an ontology-aware system and the human experts.

  5. Computable models

    CERN Document Server

    Turner, Raymond

    2009-01-01

    Computational models can be found everywhere in present day science and engineering. In providing a logical framework and foundation for the specification and design of specification languages, Raymond Turner uses this framework to introduce and study computable models. In doing so he presents the first systematic attempt to provide computational models with a logical foundation. Computable models have wide-ranging applications from programming language semantics and specification languages, through to knowledge representation languages and formalism for natural language semantics. They are al

  6. Zeebrugge Model

    DEFF Research Database (Denmark)

    Sclütter, Flemming; Frigaard, Peter; Liu, Zhou

    This report presents the model test results on wave run-up on the Zeebrugge breakwater under the simulated prototype storms. The model test was performed in January 2000 at the Hydraulics & Coastal Engineering Laboratory, Aalborg University. The detailed description of the model is given...

  7. Marginal Models

    CERN Document Server

    Bergsma, Wicher; Hagenaars, Jacques A

    2009-01-01

    Presents an overview of the basic principles of marginal modeling and offers a range of possible applications. This book includes many real world examples, explains the types of research questions for which marginal modeling is useful, and provides a description of how to apply marginal models for a great diversity of research questions.

  8. On the angular dependence and scattering model of polar mesospheric summer echoes at VHF

    Science.gov (United States)

    Sommer, Svenja; Stober, Gunter; Chau, Jorge L.

    2016-01-01

    We present measurements of the angular dependence of polar mesospheric summer echoes (PMSE) with the Middle Atmosphere Alomar Radar System in Northern Norway (69.30° N, 16.04° E). Our results are based on multireceiver and multibeam observations using beam pointing directions with off-zenith angles up to 25° as well as on spatial correlation analysis (SCA) from vertical beam observations. We consider a beam filling effect at the upper and lower boundaries of PMSE in tilted beams, which determines the effective mean angle of arrival. Comparing the average power of the vertical beam to the oblique beams suggests that PMSE are mainly not as aspect sensitive as in contrast to previous studies. However, from SCA, times of enhanced correlation are found, indicating aspect sensitivity or a localized scattering mechanism. Our results suggest that PMSE consist of nonhomogeneous isotropic scattering and previously reported aspect sensitivity values might have been influenced by the inhomogeneous nature of PMSE.

  9. Mathematical modelling

    DEFF Research Database (Denmark)

    Blomhøj, Morten

    2004-01-01

    modelling, however, can be seen as a practice of teaching that place the relation between real life and mathematics into the centre of teaching and learning mathematics, and this is relevant at all levels. Modelling activities may motivate the learning process and help the learner to establish cognitive...... roots for the construction of important mathematical concepts. In addition competences for setting up, analysing and criticising modelling processes and the possible use of models is a formative aim in this own right for mathematics teaching in general education. The paper presents a theoretical...... framework, which has been used for designing modelling courses, analysing students’ modelling activities, identifying learning obstacles in the modelling process and to guide the teachers interaction with the students during their work. This will be illustrated with an example from a developmental project...

  10. Non-model model organisms

    OpenAIRE

    Russell, James J.; Theriot, Julie A.; Sood, Pranidhi; Marshall, Wallace F.; Laura F Landweber; Fritz-Laylin, Lillian; Polka, Jessica K.; Oliferenko, Snezhana; Gerbich, Therese; Gladfelter, Amy; Umen, James; Bezanilla, Magdalena; Lancaster, Madeline A.; He, Shuonan; Matthew C Gibson

    2017-01-01

    Model organisms are widely used in research as accessible and convenient systems to study a particular area or question in biology. Traditionally only a handful of organisms have been widely studied, but modern research tools are enabling researchers to extend the set of model organisms to include less-studied and more unusual systems. This Forum highlights a range of 'non-model model organisms' as emerging systems for tackling questions across the whole spectrum of biology (and beyond), the ...

  11. Integrating stomach content and stable isotope analyses to quantify the diets of pygoscelid penguins.

    Directory of Open Access Journals (Sweden)

    Michael J Polito

    Full Text Available Stomach content analysis (SCA and more recently stable isotope analysis (SIA integrated with isotopic mixing models have become common methods for dietary studies and provide insight into the foraging ecology of seabirds. However, both methods have drawbacks and biases that may result in difficulties in quantifying inter-annual and species-specific differences in diets. We used these two methods to simultaneously quantify the chick-rearing diet of Chinstrap (Pygoscelis antarctica and Gentoo (P. papua penguins and highlight methods of integrating SCA data to increase accuracy of diet composition estimates using SIA. SCA biomass estimates were highly variable and underestimated the importance of soft-bodied prey such as fish. Two-source, isotopic mixing model predictions were less variable and identified inter-annual and species-specific differences in the relative amounts of fish and krill in penguin diets not readily apparent using SCA. In contrast, multi-source isotopic mixing models had difficulty estimating the dietary contribution of fish species occupying similar trophic levels without refinement using SCA-derived otolith data. Overall, our ability to track inter-annual and species-specific differences in penguin diets using SIA was enhanced by integrating SCA data to isotopic mixing modes in three ways: 1 selecting appropriate prey sources, 2 weighting combinations of isotopically similar prey in two-source mixing models and 3 refining predicted contributions of isotopically similar prey in multi-source models.

  12. Modelling in Business Model design

    NARCIS (Netherlands)

    Simonse, W.L.

    2013-01-01

    It appears that business model design might not always produce a design or model as the expected result. However when designers are involved, a visual model or artefact is produced. To assist strategic managers in thinking about how they can act, the designers challenge is to combine strategy and

  13. Mathematical modelling

    CERN Document Server

    2016-01-01

    This book provides a thorough introduction to the challenge of applying mathematics in real-world scenarios. Modelling tasks rarely involve well-defined categories, and they often require multidisciplinary input from mathematics, physics, computer sciences, or engineering. In keeping with this spirit of modelling, the book includes a wealth of cross-references between the chapters and frequently points to the real-world context. The book combines classical approaches to modelling with novel areas such as soft computing methods, inverse problems, and model uncertainty. Attention is also paid to the interaction between models, data and the use of mathematical software. The reader will find a broad selection of theoretical tools for practicing industrial mathematics, including the analysis of continuum models, probabilistic and discrete phenomena, and asymptotic and sensitivity analysis.

  14. Phenomenological models

    Energy Technology Data Exchange (ETDEWEB)

    Braby, L.A.

    1990-09-01

    The biological effects of ionizing radiation exposure are the result of a complex sequence of physical, chemical, biochemical, and physiological interactions. One way to begin a search for an understanding of health effects of radiation is through the development of phenomenological models of the response. Many models have been presented and tested in the slowly evolving process of characterizing cellular response. A range of models covering different endpoints and phenomena has developed in parallel. Many of these models employ similar assumptions about some underlying processes while differing about the nature of others. An attempt is made to organize many of the models into groups with similar features and to compare the consequences of those features with the actual experimental observations. It is assumed that by showing that some assumptions are inconsistent with experimental observations, the job of devising and testing mechanistic models can be simplified. 43 refs., 13 figs.

  15. Modelling Overview

    DEFF Research Database (Denmark)

    Larsen, Lars Bjørn; Vesterager, Johan

    This report provides an overview of the existing models of global manufacturing, describes the required modelling views and associated methods and identifies tools, which can provide support for this modelling activity.The model adopted for global manufacturing is that of an extended enterprise....... One or more units from beyond the network may complement the extended enterprise. The common reference model for this extended enterprise will utilise GERAM (Generalised Enterprise Reference Architecture and Methodology) to provide an architectural framework for the modelling carried out within...... sharing many of the characteristics of a virtual enterprise. This extended enterprise will have the following characteristics: The extended enterprise is focused on satisfying the current customer requirement so that it has a limited life expectancy, but should be capable of being recreated to deal...

  16. Event Modeling

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2001-01-01

    are dynamic and we present a modeling approach that can be used to model such dynamics. We characterize events as both information objects and change agents (Bækgaard 1997). When viewed as information objects events are phenomena that can be observed and described. For example, borrow events in a library can......The purpose of this chapter is to discuss conceptual event modeling within a context of information modeling. Traditionally, information modeling has been concerned with the modeling of a universe of discourse in terms of information structures. However, most interesting universes of discourse...... be characterized by their occurrence times and the participating books and borrowers. When we characterize events as information objects we focus on concepts like information structures. When viewed as change agents events are phenomena that trigger change. For example, when borrow event occurs books are moved...

  17. Mental models

    OpenAIRE

    Marco Antonio Moreira

    1996-01-01

    The mental models subject is presented particularly in the light of Johnson-Laird’s theory. Views from different authors are also presented but the emphasis lies in Johson-Laird’s approach, proposing mental models as a third path in the images x propositions debate. In this perspective, the nature, content, and typology of mental models are discussed, as well as the issue of conciousness and computability. In addition, the methodology of research studies are provided. Essentially, the aim of ...

  18. Spherical models

    CERN Document Server

    Wenninger, Magnus J

    2012-01-01

    Well-illustrated, practical approach to creating star-faced spherical forms that can serve as basic structures for geodesic domes. Complete instructions for making models from circular bands of paper with just a ruler and compass. Discusses tessellation, or tiling, and how to make spherical models of the semiregular solids and concludes with a discussion of the relationship of polyhedra to geodesic domes and directions for building models of domes. "". . . very pleasant reading."" - Science. 1979 edition.

  19. Zeebrugge Model

    DEFF Research Database (Denmark)

    Liu, Zhou; Frigaard, Peter

    This report presents the model on wave run-up and run-down on the Zeebrugge breakwater under short-crested oblique wave attacks. The model test was performed in March-April 2000 at the Hydraulics & Coastal Engineering Laboratory, Aalborg University.......This report presents the model on wave run-up and run-down on the Zeebrugge breakwater under short-crested oblique wave attacks. The model test was performed in March-April 2000 at the Hydraulics & Coastal Engineering Laboratory, Aalborg University....

  20. Mental models

    Directory of Open Access Journals (Sweden)

    Marco Antonio Moreira

    1996-12-01

    Full Text Available The mental models subject is presented particularly in the light of Johnson-Laird’s theory. Views from different authors are also presented but the emphasis lies in Johson-Laird’s approach, proposing mental models as a third path in the images x propositions debate. In this perspective, the nature, content, and typology of mental models are discussed, as well as the issue of conciousness and computability. In addition, the methodology of research studies are provided. Essentially, the aim of the paper is to provide an introduction to the mental models topic, having science education research in mind.

  1. Turbulence Model

    DEFF Research Database (Denmark)

    Nielsen, Mogens Peter; Shui, Wan; Johansson, Jens

    2011-01-01

    In this report a new turbulence model is presented.In contrast to the bulk of modern work, the model is a classical continuum model with a relatively simple constitutive equation. The constitutive equation is, as usual in continuum mechanics, entirely empirical. It has the usual Newton or Stokes...... term with stresses depending linearly on the strain rates. This term takes into account the transfer of linear momentum from one part of the fluid to another. Besides there is another term, which takes into account the transfer of angular momentum. Thus the model implies a new definition of turbulence...

  2. Modeling Documents with Event Model

    Directory of Open Access Journals (Sweden)

    Longhui Wang

    2015-08-01

    Full Text Available Currently deep learning has made great breakthroughs in visual and speech processing, mainly because it draws lessons from the hierarchical mode that brain deals with images and speech. In the field of NLP, a topic model is one of the important ways for modeling documents. Topic models are built on a generative model that clearly does not match the way humans write. In this paper, we propose Event Model, which is unsupervised and based on the language processing mechanism of neurolinguistics, to model documents. In Event Model, documents are descriptions of concrete or abstract events seen, heard, or sensed by people and words are objects in the events. Event Model has two stages: word learning and dimensionality reduction. Word learning is to learn semantics of words based on deep learning. Dimensionality reduction is the process that representing a document as a low dimensional vector by a linear mode that is completely different from topic models. Event Model achieves state-of-the-art results on document retrieval tasks.

  3. Virtual modeling

    NARCIS (Netherlands)

    Flores, J.; Kiss, S.; Cano, P.; Nijholt, Antinus; Zwiers, Jakob

    2003-01-01

    We concentrate our efforts on building virtual modelling environments where the content creator uses controls (widgets) as an interactive adjustment modality for the properties of the edited objects. Besides the advantage of being an on-line modelling approach (visualised just like any other on-line

  4. Education models

    NARCIS (Netherlands)

    Poortman, Sybilla; Sloep, Peter

    2006-01-01

    Educational models describes a case study on a complex learning object. Possibilities are investigated for using this learning object, which is based on a particular educational model, outside of its original context. Furthermore, this study provides advice that might lead to an increase in

  5. Battery Modeling

    NARCIS (Netherlands)

    Jongerden, M.R.; Haverkort, Boudewijn R.H.M.

    2008-01-01

    The use of mobile devices is often limited by the capacity of the employed batteries. The battery lifetime determines how long one can use a device. Battery modeling can help to predict, and possibly extend this lifetime. Many different battery models have been developed over the years. However,

  6. Scribe modeller

    DEFF Research Database (Denmark)

    Løssing, Ulrik

    1986-01-01

    Ulrik Løssing har redigeret, illustreret og oversat: "Scribe Modeller System, Sheffield, november 1985" af forfatterne: Cedric Green, David Cooper og John Wells.......Ulrik Løssing har redigeret, illustreret og oversat: "Scribe Modeller System, Sheffield, november 1985" af forfatterne: Cedric Green, David Cooper og John Wells....

  7. Interface models

    DEFF Research Database (Denmark)

    Ravn, Anders P.; Staunstrup, Jørgen

    1994-01-01

    This paper proposes a model for specifying interfaces between concurrently executing modules of a computing system. The model does not prescribe a particular type of communication protocol and is aimed at describing interfaces between both software and hardware modules or a combination of the two...

  8. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...... pathology, to biomarkers in diagnosis and prognostic evaluation, to drug testing and targeted medicine....

  9. Didactical modelling

    DEFF Research Database (Denmark)

    Højgaard, Tomas; Hansen, Rune

    The purpose of this paper is to introduce Didactical Modelling as a research methodology in mathematics education. We compare the methodology with other approaches and argue that Didactical Modelling has its own specificity. We discuss the methodological “why” and explain why we find it useful...

  10. Modelling Constructs

    DEFF Research Database (Denmark)

    Kindler, Ekkart

    2009-01-01

    , these notations have been extended in order to increase expressiveness and to be more competitive. This resulted in an increasing number of notations and formalisms for modelling business processes and in an increase of the different modelling constructs provided by modelling notations, which makes it difficult...... to compare modelling notations and to make transformations between them. One of the reasons is that, in each notation, the new concepts are introduced in a different way by extending the already existing constructs. In this chapter, we go the opposite direction: We show that it is possible to add most...... constructs and how they can be combined with more advanced constructs. Second, it will help combining different modelling notations with each other. Note that, though we introduce a notation for blocks in this chapter, we are not so much interested in promoting this notation here. The notation should just...

  11. OSPREY Model

    Energy Technology Data Exchange (ETDEWEB)

    Veronica J. Rutledge

    2013-01-01

    The absence of industrial scale nuclear fuel reprocessing in the U.S. has precluded the necessary driver for developing the advanced simulation capability now prevalent in so many other countries. Thus, it is essential to model complex series of unit operations to simulate, understand, and predict inherent transient behavior and feedback loops. A capability of accurately simulating the dynamic behavior of advanced fuel cycle separation processes will provide substantial cost savings and many technical benefits. The specific fuel cycle separation process discussed in this report is the off-gas treatment system. The off-gas separation consists of a series of scrubbers and adsorption beds to capture constituents of interest. Dynamic models are being developed to simulate each unit operation involved so each unit operation can be used as a stand-alone model and in series with multiple others. Currently, an adsorption model has been developed within Multi-physics Object Oriented Simulation Environment (MOOSE) developed at the Idaho National Laboratory (INL). Off-gas Separation and REcoverY (OSPREY) models the adsorption of off-gas constituents for dispersed plug flow in a packed bed under non-isothermal and non-isobaric conditions. Inputs to the model include gas, sorbent, and column properties, equilibrium and kinetic data, and inlet conditions. The simulation outputs component concentrations along the column length as a function of time from which breakthrough data is obtained. The breakthrough data can be used to determine bed capacity, which in turn can be used to size columns. It also outputs temperature along the column length as a function of time and pressure drop along the column length. Experimental data and parameters were input into the adsorption model to develop models specific for krypton adsorption. The same can be done for iodine, xenon, and tritium. The model will be validated with experimental breakthrough curves. Customers will be given access to

  12. Análisis molecular de las ataxias espinocerebelosas para los genes 1,2,3,6,7,8 y FRDA en la población colombiana

    Directory of Open Access Journals (Sweden)

    Durán C.

    2001-06-01

    Full Text Available Las ataxias son un grupo de enfermedades neurodegenerativas que afectan el cerebelo, el tallo y los tractos espinocerebelosos. 10 genes para las ataxias espinocerebelosas (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12, SCA13, y DRPLA han sido clonados y han permitido la clasificación genética de estas patologías.

  13. Graphical Rasch models

    DEFF Research Database (Denmark)

    Kreiner, Svend; Christensen, Karl Bang

    Rasch models; Partial Credit models; Rating Scale models; Item bias; Differential item functioning; Local independence; Graphical models......Rasch models; Partial Credit models; Rating Scale models; Item bias; Differential item functioning; Local independence; Graphical models...

  14. Modeling complexes of modeled proteins.

    Science.gov (United States)

    Anishchenko, Ivan; Kundrotas, Petras J; Vakser, Ilya A

    2017-03-01

    Structural characterization of proteins is essential for understanding life processes at the molecular level. However, only a fraction of known proteins have experimentally determined structures. This fraction is even smaller for protein-protein complexes. Thus, structural modeling of protein-protein interactions (docking) primarily has to rely on modeled structures of the individual proteins, which typically are less accurate than the experimentally determined ones. Such "double" modeling is the Grand Challenge of structural reconstruction of the interactome. Yet it remains so far largely untested in a systematic way. We present a comprehensive validation of template-based and free docking on a set of 165 complexes, where each protein model has six levels of structural accuracy, from 1 to 6 Å C α RMSD. Many template-based docking predictions fall into acceptable quality category, according to the CAPRI criteria, even for highly inaccurate proteins (5-6 Å RMSD), although the number of such models (and, consequently, the docking success rate) drops significantly for models with RMSD > 4 Å. The results show that the existing docking methodologies can be successfully applied to protein models with a broad range of structural accuracy, and the template-based docking is much less sensitive to inaccuracies of protein models than the free docking. Proteins 2017; 85:470-478. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Correct Models

    OpenAIRE

    Blacher, René

    2010-01-01

    Ce rapport complete les deux rapports précédents et apporte une explication plus simple aux résultats précédents : à savoir la preuve que les suites obtenues sont aléatoires.; In previous reports, we have show how to transform a text $y_n$ in a random sequence by using functions of Fibonacci $T_q$. Now, in this report, we obtain a clearer result by proving that $T_q(y_n)$ has the IID model as correct model. But, it is necessary to define correctly a correct model. Then, we study also this pro...

  16. Model theory

    CERN Document Server

    Hodges, Wilfrid

    1993-01-01

    An up-to-date and integrated introduction to model theory, designed to be used for graduate courses (for students who are familiar with first-order logic), and as a reference for more experienced logicians and mathematicians.

  17. Paleoclimate Modeling

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Computer simulations of past climate. Variables provided as model output are described by parameter keyword. In some cases the parameter keywords are a subset of all...

  18. Linear Models

    CERN Document Server

    Searle, Shayle R

    2012-01-01

    This 1971 classic on linear models is once again available--as a Wiley Classics Library Edition. It features material that can be understood by any statistician who understands matrix algebra and basic statistical methods.

  19. Environmental Modeling

    Science.gov (United States)

    EPA's modeling community is working to gain insights into certain parts of a physical, biological, economic, or social system by conducting environmental assessments for Agency decision making to complex environmental issues.

  20. Stream Modelling

    DEFF Research Database (Denmark)

    Vestergaard, Kristian

    The development of the digital computer has been of great importance for the hydraulic engineer. Through many centuries hydraulic engineering was based on practical know-how, obtained through many hundred years experience. Gradually mathematical theories were introduced and accepted among...... the engineers, but as the scale and the complexity of the hydraulic works increased, the mathematical models became so complex that a mathematical solution could not be obtained. This created a demand for new methods and again the experimental investigation became popular, but this time as measurements on small......-scale models. But still the scale and complexity of hydraulic works were increasing, and soon even small-scale models reached a natural limit for some applications. In the mean time the modern computer was developed, and it became possible to solve complex mathematical models by use of computer-based numerical...

  1. Anchor Modeling

    Science.gov (United States)

    Regardt, Olle; Rönnbäck, Lars; Bergholtz, Maria; Johannesson, Paul; Wohed, Petia

    Maintaining and evolving data warehouses is a complex, error prone, and time consuming activity. The main reason for this state of affairs is that the environment of a data warehouse is in constant change, while the warehouse itself needs to provide a stable and consistent interface to information spanning extended periods of time. In this paper, we propose a modeling technique for data warehousing, called anchor modeling, that offers non-destructive extensibility mechanisms, thereby enabling robust and flexible management of changes in source systems. A key benefit of anchor modeling is that changes in a data warehouse environment only require extensions, not modifications, to the data warehouse. This ensures that existing data warehouse applications will remain unaffected by the evolution of the data warehouse, i.e. existing views and functions will not have to be modified as a result of changes in the warehouse model.

  2. Trends in Sierra Nevada snowmelt based on 10 years of MODIS fractional snow covered area data: the apparent and the missing (Invited)

    Science.gov (United States)

    Bales, R. C.; Rice, R.; Rittger, K. E.; Painter, T. H.

    2009-12-01

    The availability of accurate, fractional snow covered area (SCA) from MODIS and follow-on satellites on a daily basis offers unprecedented detail on snow accumulation and melt across variable terrain. Despite differences in elevation, latitude and accumulation, there is a remarkable consistency to snowmelt patterns with elevation across the Sierra Nevada. In the spring, melt out of the landscape, defined here as SCA MODSCAG (MODIS Snow Covered Area and Grain size/albedo) model provides a daily estimate of SCA across complex terrain that avoids some of the inherent biases in a binary SCA product. In addition, interpolation methods have been introduced to account for missing data; however forest cover and complex terrain introduce potential biases. Use of MODIS in basin-scale hydrologic modeling, i.e. 100’s to 1,000’s of km2, can safely ignore these biases at larger scales and lighter forest cover. But in smaller basins where many pixels are only partly in the basin and vegetation may obscure significant snow on the ground, these negative biases need to be addressed. For example, in dense canopy MODIS fractional SCA was observed to reach zero when on-the-ground snow surveys still showed on the order of 5-15% SCA. With a 30-m pixel size, LANDSAT pushes the limits of the scale-dependent biases to much smaller basins; however snow under the canopy cannot be captured directly by any optical sensor. It should also be noted that the MODSCAG and LANDSAT products currently available have a cutoff of 15% SCA for any given pixel. Empirical corrections provide low-SCA estimates and canopy corrections.

  3. Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi

    2016-01-01

    effects, unicausal reduction, and case specificity. Based on the developments in set theoretical thinking in social sciences and employing methods like Qualitative Comparative Analysis (QCA), Necessary Condition Analysis (NCA), and set visualization techniques, in this position paper, we propose...... and demonstrate a new approach to maturity models in the domain of Information Systems. This position paper describes the set-theoretical approach to maturity models, presents current results and outlines future research work....

  4. Association of a 62 Variant Type 2 Diabetes Genetic Risk Score with Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study

    Science.gov (United States)

    Dauriz, Marco; Porneala, Bianca C.; Guo, Xiuqing; Bielak, Lawrence F.; Peyser, Patricia A.; Durant, Nefertiti H.; Carnethon, Mercedes R.; Bonadonna, Riccardo C.; Bonora, Enzo; Bowden, Donald W.; Florez, Jose C.; Fornage, Myriam; Hivert, Marie-France; Jacobs, David R.; Kabagambe, Edmond K.; Lewis, Cora E.; Murabito, Joanne M.; Rasmussen-Torvik, Laura J.; Rich, Stephen S.; Vassy, Jason L.; Yao, Jie; Carr, Jeffrey J.; Kardia, Sharon L.R.; Siscovick, David; O'Donnell, Christopher J.; Rotter, Jerome I.; Dupuis, Josée; Meigs, James B.

    2015-01-01

    Background Type 2 diabetes (T2D) and cardiovascular disease (CVD) share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results In a cross-sectional analysis including up to 9,210 European Americans, 3,773 African Americans, 1,446 Hispanic Americans and 773 Chinese Americans without known CVD and enrolled in the FHS, CARDIA, MESA and GENOA studies, we tested a 62 T2D-loci genetic risk score (GRS62) for association with measures of SCA, including coronary artery (CACS) or abdominal aortic calcium score, common (CCA-IMT) and internal carotid artery intima-media thickness, and ankle-brachial index (ABI). We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors adjusted model (significance = pidentified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and CVD risk loci. PMID:25805414

  5. Accelerated life models modeling and statistical analysis

    CERN Document Server

    Bagdonavicius, Vilijandas

    2001-01-01

    Failure Time DistributionsIntroductionParametric Classes of Failure Time DistributionsAccelerated Life ModelsIntroductionGeneralized Sedyakin's ModelAccelerated Failure Time ModelProportional Hazards ModelGeneralized Proportional Hazards ModelsGeneralized Additive and Additive-Multiplicative Hazards ModelsChanging Shape and Scale ModelsGeneralizationsModels Including Switch-Up and Cycling EffectsHeredity HypothesisSummaryAccelerated Degradation ModelsIntroductionDegradation ModelsModeling the Influence of Explanatory Varia

  6. Mechanistic models

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, S.B.

    1990-09-01

    Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (1) interaction'' of lesions produced by statistically independent particle tracks; (2) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (3) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the RMR and LPL models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.

  7. Mechanistic models

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, S.B.

    1990-09-01

    Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (1) ``interaction`` of lesions produced by statistically independent particle tracks; (2) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (3) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the RMR and LPL models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.

  8. Mathematical modeling

    CERN Document Server

    Eck, Christof; Knabner, Peter

    2017-01-01

    Mathematical models are the decisive tool to explain and predict phenomena in the natural and engineering sciences. With this book readers will learn to derive mathematical models which help to understand real world phenomena. At the same time a wealth of important examples for the abstract concepts treated in the curriculum of mathematics degrees are given. An essential feature of this book is that mathematical structures are used as an ordering principle and not the fields of application. Methods from linear algebra, analysis and the theory of ordinary and partial differential equations are thoroughly introduced and applied in the modeling process. Examples of applications in the fields electrical networks, chemical reaction dynamics, population dynamics, fluid dynamics, elasticity theory and crystal growth are treated comprehensively.

  9. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident...... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....

  10. Lens Model

    DEFF Research Database (Denmark)

    Nash, Ulrik William

    2014-01-01

    Firms consist of people who make decisions to achieve goals. How do these people develop the expectations which underpin the choices they make? The lens model provides one answer to this question. It was developed by cognitive psychologist Egon Brunswik (1952) to illustrate his theory of probabil......Firms consist of people who make decisions to achieve goals. How do these people develop the expectations which underpin the choices they make? The lens model provides one answer to this question. It was developed by cognitive psychologist Egon Brunswik (1952) to illustrate his theory...... of probabilistic functionalism, and concerns the environment and the mind, and adaptation by the latter to the former. This entry is about the lens model, and probabilistic functionalism more broadly. Focus will mostly be on firms and their employees, but, to fully appreciate the scope, we have to keep in mind...

  11. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary...

  12. Modelling osteomyelitis

    Science.gov (United States)

    2012-01-01

    Background This work focuses on the computational modelling of osteomyelitis, a bone pathology caused by bacteria infection (mostly Staphylococcus aureus). The infection alters the RANK/RANKL/OPG signalling dynamics that regulates osteoblasts and osteoclasts behaviour in bone remodelling, i.e. the resorption and mineralization activity. The infection rapidly leads to severe bone loss, necrosis of the affected portion, and it may even spread to other parts of the body. On the other hand, osteoporosis is not a bacterial infection but similarly is a defective bone pathology arising due to imbalances in the RANK/RANKL/OPG molecular pathway, and due to the progressive weakening of bone structure. Results Since both osteoporosis and osteomyelitis cause loss of bone mass, we focused on comparing the dynamics of these diseases by means of computational models. Firstly, we performed meta-analysis on a gene expression data of normal, osteoporotic and osteomyelitis bone conditions. We mainly focused on RANKL/OPG signalling, the TNF and TNF receptor superfamilies and the NF-kB pathway. Using information from the gene expression data we estimated parameters for a novel model of osteoporosis and of osteomyelitis. Our models could be seen as a hybrid ODE and probabilistic verification modelling framework which aims at investigating the dynamics of the effects of the infection in bone remodelling. Finally we discuss different diagnostic estimators defined by formal verification techniques, in order to assess different bone pathologies (osteopenia, osteoporosis and osteomyelitis) in an effective way. Conclusions We present a modeling framework able to reproduce aspects of the different bone remodeling defective dynamics of osteomyelitis and osteoporosis. We report that the verification-based estimators are meaningful in the light of a feed forward between computational medicine and clinical bioinformatics. PMID:23095605

  13. Modelling language

    CERN Document Server

    Cardey, Sylviane

    2013-01-01

    In response to the need for reliable results from natural language processing, this book presents an original way of decomposing a language(s) in a microscopic manner by means of intra/inter‑language norms and divergences, going progressively from languages as systems to the linguistic, mathematical and computational models, which being based on a constructive approach are inherently traceable. Languages are described with their elements aggregating or repelling each other to form viable interrelated micro‑systems. The abstract model, which contrary to the current state of the art works in int

  14. Model SIR

    OpenAIRE

    Koprivnikar, Teja

    2017-01-01

    Epidemiološki modeli širjenja nalezljivih bolezni so matematični modeli, ki poskušajo pojasniti, kako se širijo nalezljive bolezni. Eden najbolj znanih modelov je model SIR. Leta 1927 sta ga oblikovala Kermack in McKendrick, zapišemo pa ga lahko s sistemom treh diferencialnih enačb. Proučevanje le-teh nam omogoča napovedovanje obnašanja določene bolezni v populaciji in s tem napoved, ali bo epidemija izbruhnila ali ne. V diplomskem delu predstavimo in analiziramo omenjeni model ter poskušamo ...

  15. Molecular Modeling

    Science.gov (United States)

    Holmes, Jon L.

    1999-06-01

    Molecular modeling has trickled down from the realm of pharmaceutical and research laboratories into the realm of undergraduate chemistry instruction. It has opened avenues for the visualization of chemical concepts that previously were difficult or impossible to convey. I am sure that many of you have developed exercises using the various molecular modeling tools. It is the desire of this Journal to become an avenue for you to share these exercises among your colleagues. It is to this end that Ron Starkey has agreed to edit such a column and to publish not only the description of such exercises, but also the software documents they use. The WWW is the obvious medium to distribute this combination and so accepted submissions will appear online as a feature of JCE Internet. Typical molecular modeling exercise: finding conformation energies. Molecular Modeling Exercises and Experiments is the latest feature column of JCE Internet, joining Conceptual Questions and Challenge Problems, Hal's Picks, and Mathcad in the Chemistry Curriculum. JCE Internet continues to seek submissions in these areas of interest and submissions of general interest. If you have developed materials and would like to submit them, please see our Guide to Submissions for more information. The Chemical Education Resource Shelf, Equipment Buyers Guide, and WWW Site Review would also like to hear about chemistry textbooks and software, equipment, and WWW sites, respectively. Please consult JCE Internet Features to learn more about these resources at JCE Online. Email Announcements Would you like to be informed by email when the latest issue of the Journal is available online? when a new JCE Software title is shipping? when a new JCE Internet article has been published or is available for Open Review? when your subscription is about to expire? A new feature of JCE Online makes this possible. Visit our Guestbook to learn how. When you submit the form on this page, which includes your email address

  16. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  17. Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3

    Directory of Open Access Journals (Sweden)

    Susanne K. Hansen

    2016-09-01

    Full Text Available The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3 is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method and the resulting SCA3 iPSCs were differentiated into neurons. These neuronal lines harbored the disease causing mutation, expressed comparable levels of several neuronal markers and responded to the neurotransmitters, glutamate/glycine, GABA and acetylcholine. Additionally, all neuronal cultures formed networks displaying synchronized spontaneous calcium oscillations within 28 days of maturation, and expressed the mature neuronal markers NeuN and Synapsin 1 implying a relatively advanced state of maturity, although not comparable to that of the adult human brain. Interestingly, we were not able to recapitulate the glutamate-induced ataxin-3 aggregation shown in a previously published iPSC-derived SCA3 model. In conclusion, we have generated a panel of SCA3 patient iPSCs and a robust protocol to derive neurons of relatively advanced maturity, which could potentially be valuable for the study of SCA3 disease mechanisms.

  18. Isentropic transport and the seasonal cycle amplitude of CO2

    Science.gov (United States)

    Parazoo, N.; Barnes, E. A.; Orbe, C.; Denning, A. S.

    2016-12-01

    Carbon-concentration feedbacks and carbon-climate feedbacks constitute one of the largest sources of uncertainty in future climate. Since the beginning of the modern atmospheric CO2 record, seasonal variations in CO2 have been recognized as a signal of the metabolism of land ecosystems, and quantitative attribution of changes in the seasonal cycle amplitude (SCA) of CO2 to ecosystem processes is critical for understanding and projecting carbon-climate feedbacks far into the 21st Century. Here the impact of surface carbon fluxes on the SCA of CO2 throughout the Northern Hemisphere troposphere is investigated, paying particular attention to isentropic transport across latitudes. The analysis includes both a chemical transport model GOES-Chem and an idealized tracer in a gray-radiation aquaplanet. The results of the study can be summarized by two main conclusions: (1) the SCA of CO2 roughly follows surfaces of constant potential temperature, which can explain the observed increase in SCA with latitude along pressure surfaces and (2) increasing seasonal fluxes in lower latitudes have a larger impact on the SCA of CO2 throughout most of the troposphere compared to increasing seasonal fluxes in higher latitudes. These results provide strong evidence that recently observed changes in the SCA of CO2 at high northern latitudes (poleward of 60N) are likely driven by changes in midlatitude surface fluxes, rather than changes in Arctic fluxes.

  19. Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair

    Science.gov (United States)

    Kumar, Varsha Suresh; Zhang, Wei; Rehman, Jalees; Malik, Asrar B.

    2015-01-01

    The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa–induced lung injury, we identified a population of stem cell antigen (Sca)-1–expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1–expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C+Sca-1+ cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C+Sca-1+ cells in vitro. Thus, P. aeruginosa–mediated lung injury induces the generation of a Sca-1+ subset of type II cells. The progenitor phenotype of the Sp-C+Sca-1+ cells that mediates alveolar epithelial repair might involve Wnt signaling. PMID:25474582

  20. Building Models and Building Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Kaj; Skauge, Jørn

    2008-01-01

    I rapportens indledende kapitel beskrives de primære begreber vedrørende bygningsmodeller og nogle fundamentale forhold vedrørende computerbaseret modulering bliver opstillet. Desuden bliver forskellen mellem tegneprogrammer og bygnings­model­lerings­programmer beskrevet. Vigtige aspekter om......­lering og bygningsmodeller. Det bliver understreget at modellering bør udføres på flere abstraktions­niveauer og i to dimensioner i den såkaldte modelleringsmatrix. Ud fra dette identificeres de primære faser af bygningsmodel­lering. Dernæst beskrives de basale karakteristika for bygningsmodeller. Heri...... inkluderes en præcisering af begreberne objektorienteret software og objektorienteret modeller. Det bliver fremhævet at begrebet objektbaseret modellering giver en tilstrækkelig og bedre forståelse. Endelig beskrives forestillingen om den ideale bygningsmodel som værende én samlet model, der anvendes gennem...

  1. Modeling Muscles

    Science.gov (United States)

    Goodwyn, Lauren; Salm, Sarah

    2007-01-01

    Teaching the anatomy of the muscle system to high school students can be challenging. Students often learn about muscle anatomy by memorizing information from textbooks or by observing plastic, inflexible models. Although these mediums help students learn about muscle placement, the mediums do not facilitate understanding regarding integration of…

  2. Zeebrugge Model

    DEFF Research Database (Denmark)

    Jensen, Morten S.; Frigaard, Peter

    In the following, results from model tests with Zeebrugge breakwater are presented. The objective with these tests is partly to investigate the influence on wave run-up due to a changing waterlevel during a storm. Finally, the influence on wave run-up due to an introduced longshore current...

  3. Model Checking

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 7. Model Checking - Automated Verification of Computational Systems. Madhavan Mukund. General Article Volume 14 Issue 7 July 2009 pp 667-681. Fulltext. Click here to view fulltext PDF. Permanent link:

  4. Cosmological models

    Energy Technology Data Exchange (ETDEWEB)

    Hajj-Boutros, J. (Lebanese Univ., Mansourieh-El-Maten (Lebanon))

    1989-04-01

    An LRS Bianchi type II cosmological model is built with a state equation that is a function of the cosmic time t. The ratio p/{mu} is 1/3 when t {yields} 0 and is insignificant when t {yields} {infinity}. Thus, the matter content behaves like radiation for small t and like dust for large t.

  5. Painting models

    Science.gov (United States)

    Baart, F.; Donchyts, G.; van Dam, A.; Plieger, M.

    2015-12-01

    The emergence of interactive art has blurred the line between electronic, computer graphics and art. Here we apply this art form to numerical models. Here we show how the transformation of a numerical model into an interactive painting can both provide insights and solve real world problems. The cases that are used as an example include forensic reconstructions, dredging optimization, barrier design. The system can be fed using any source of time varying vector fields, such as hydrodynamic models. The cases used here, the Indian Ocean (HYCOM), the Wadden Sea (Delft3D Curvilinear), San Francisco Bay (3Di subgrid and Delft3D Flexible Mesh), show that the method used is suitable for different time and spatial scales. High resolution numerical models become interactive paintings by exchanging their velocity fields with a high resolution (>=1M cells) image based flow visualization that runs in a html5 compatible web browser. The image based flow visualization combines three images into a new image: the current image, a drawing, and a uv + mask field. The advection scheme that computes the resultant image is executed in the graphics card using WebGL, allowing for 1M grid cells at 60Hz performance on mediocre graphic cards. The software is provided as open source software. By using different sources for a drawing one can gain insight into several aspects of the velocity fields. These aspects include not only the commonly represented magnitude and direction, but also divergence, topology and turbulence .

  6. Markov model

    Indian Academy of Sciences (India)

    Improper practices of land use and land cover (LULC) including deforestation, expansion of agriculture and infrastructure development are deteriorating watershed conditions. Here, we have utilized remote sensing and GIS tools to study LULC dynamics using Cellular Automata (CA)–Markov model and pre- dicted the ...

  7. Modelling Defiguration

    DEFF Research Database (Denmark)

    Bork Petersen, Franziska

    2013-01-01

    catwalks. Vibskov’s catwalk induces what the dance scholar Gabriele Brandstetter has labelled a ‘defigurative choregoraphy’: a straying from definitions, which exist in ballet as in other movement-based genres, of how a figure should move and appear (1998). The catwalk scenography in this instance...... focus centres on how the catwalk scenography evokes a ‘defiguration’ of the walking models and to what effect. Vibskov’s mobile catwalk draws attention to the walk, which is a key element of models’ performance but which usually functions in fashion shows merely to present clothes in the most...... advantageous manner. Stepping on the catwalk’s sloping, moving surfaces decelerates the models’ walk and makes it cautious, hesitant and shaky: suddenly the models lack exactly the affirmative, staccato, striving quality of motion, and the condescending expression that they perform on most contemporary...

  8. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....... on this subject, this book makes essential reading for anyone considering new ways of thinking about architecture. In drawing upon both historical and contemporary perspectives this book provides evidence of the ways in which relations between representation and the represented continue to be reconsidered...

  9. Acyclic models

    CERN Document Server

    Barr, Michael

    2002-01-01

    Acyclic models is a method heavily used to analyze and compare various homology and cohomology theories appearing in topology and algebra. This book is the first attempt to put together in a concise form this important technique and to include all the necessary background. It presents a brief introduction to category theory and homological algebra. The author then gives the background of the theory of differential modules and chain complexes over an abelian category to state the main acyclic models theorem, generalizing and systemizing the earlier material. This is then applied to various cohomology theories in algebra and topology. The volume could be used as a text for a course that combines homological algebra and algebraic topology. Required background includes a standard course in abstract algebra and some knowledge of topology. The volume contains many exercises. It is also suitable as a reference work for researchers.

  10. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  11. Modelling Behaviour

    DEFF Research Database (Denmark)

    This book reflects and expands on the current trend in the building industry to understand, simulate and ultimately design buildings by taking into consideration the interlinked elements and forces that act on them. This approach overcomes the traditional, exclusive focus on building tasks, while....... The chapter authors were invited speakers at the 5th Symposium "Modelling Behaviour", which took place at the CITA in Copenhagen in September 2015....

  12. Cheating models

    DEFF Research Database (Denmark)

    Arnoldi, Jakob

    The article discusses the use of algorithmic models for so-called High Frequency Trading (HFT) in finance. HFT is controversial yet widespread in modern financial markets. It is a form of automated trading technology which critics among other things claim can lead to market manipulation. Drawing....... The article analyses these challenges and argues that we witness a new post-social form of human-technology interaction that will lead to a reconfiguration of professional codes for financial trading....

  13. Modeling biomembranes.

    Energy Technology Data Exchange (ETDEWEB)

    Plimpton, Steven James; Heffernan, Julieanne; Sasaki, Darryl Yoshio; Frischknecht, Amalie Lucile; Stevens, Mark Jackson; Frink, Laura J. Douglas

    2005-11-01

    Understanding the properties and behavior of biomembranes is fundamental to many biological processes and technologies. Microdomains in biomembranes or ''lipid rafts'' are now known to be an integral part of cell signaling, vesicle formation, fusion processes, protein trafficking, and viral and toxin infection processes. Understanding how microdomains form, how they depend on membrane constituents, and how they act not only has biological implications, but also will impact Sandia's effort in development of membranes that structurally adapt to their environment in a controlled manner. To provide such understanding, we created physically-based models of biomembranes. Molecular dynamics (MD) simulations and classical density functional theory (DFT) calculations using these models were applied to phenomena such as microdomain formation, membrane fusion, pattern formation, and protein insertion. Because lipid dynamics and self-organization in membranes occur on length and time scales beyond atomistic MD, we used coarse-grained models of double tail lipid molecules that spontaneously self-assemble into bilayers. DFT provided equilibrium information on membrane structure. Experimental work was performed to further help elucidate the fundamental membrane organization principles.

  14. MODEL-MODEL PENILAIAN SEKURITAS

    OpenAIRE

    Imron Rosyadi

    2006-01-01

    The valuation of securities is very important, it caused by the target of financial management that was to maximize the wealth of stockholder by means of maximize value of the firm. In this article, the writer showed the valuation models of securities such as, obligation, common stock, and preference stock. The obligation value is present value from annuity (payment of fixed interest rate each period) and added by present value of principal loan. Whereas in valuation of stock, at ...

  15. From Reference Model to Component Model

    OpenAIRE

    Albani, Antonia; Zaha, Johannes Maria

    2005-01-01

    Stable component models are an essential prerequisite for developingcustomer-individual business applications. Thereby the information for theidentification and specification of their components is gained from domainmodels. Reference models constitute a potential source for building enterprisespecificdomain models. Based on the analysis of existing reference models,this article shows how information available through reference models can beused for the development of stable component models. ...

  16. Cadastral Modeling

    DEFF Research Database (Denmark)

    Stubkjær, Erik

    2005-01-01

    to the modeling of an industrial sector, as it aims at rendering the basic concepts that relate to the domain of real estate and the pertinent human activities. The palpable objects are pieces of land and buildings, documents, data stores and archives, as well as persons in their diverse roles as owners, holders...... of assets, experts, and holders of authority. More subtle objects are rights and restrictions, which relate persons through enforceable rules and commitments. The objective of this fabric of complex relations is to provide a stable and yet flexible frame for legal-economic dispositions that are related...

  17. Relationship between the clinical global impression of severity for schizoaffective disorder scale and established mood scales for mania and depression.

    Science.gov (United States)

    Turkoz, Ibrahim; Fu, Dong-Jing; Bossie, Cynthia A; Sheehan, John J; Alphs, Larry

    2013-08-15

    This analysis explored the relationship between ratings on HAM-D-17 or YMRS and those on the depressive or manic subscale of CGI-S for schizoaffective disorder (CGI-S-SCA). This post hoc analysis used the database (N=614) from two 6-week, randomized, placebo-controlled studies of paliperidone ER versus placebo in symptomatic subjects with schizoaffective disorder assessed using HAM-D-17, YMRS, and CGI-S-SCA scales. Parametric and nonparametric regression models explored the relationships between ratings on YMRS and HAM-D-17 and on depressive and manic domains of the CGI-S-SCA from baseline to the 6-week end point. A clinically meaningful improvement was defined as a change of 1 point in the CGI-S-SCA score. No adjustment was made for multiplicity. Multiple linear regression models suggested that a 1-point change in the depressive domain of CGI-S-SCA corresponded to an average 3.6-point (SE=0.2) change in HAM-D-17 score. Similarly, a 1-point change in the manic domain of CGI-S-SCA corresponded to an average 5.8-point (SE=0.2) change in YMRS score. Results were confirmed using local and cumulative logistic regression models in addition to equipercentile linking. Lack of subjects scoring over the complete range of possible scores may limit broad application of the analyses. Clinically meaningful score changes in depressive and manic domains of CGI-S-SCA corresponded to approximately 4- and 6-point score changes on HAM-D-17 and YMRS, respectively, in symptomatic subjects with schizoaffective disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. ALEPH model

    CERN Multimedia

    1989-01-01

    A wooden model of the ALEPH experiment and its cavern. ALEPH was one of 4 experiments at CERN's 27km Large Electron Positron collider (LEP) that ran from 1989 to 2000. During 11 years of research, LEP's experiments provided a detailed study of the electroweak interaction. Measurements performed at LEP also proved that there are three – and only three – generations of particles of matter. LEP was closed down on 2 November 2000 to make way for the construction of the Large Hadron Collider in the same tunnel. The cavern and detector are in separate locations - the cavern is stored at CERN and the detector is temporarily on display in Glasgow physics department. Both are available for loan.

  19. Discrete choice models

    Directory of Open Access Journals (Sweden)

    Boštjan Kerbler

    2006-01-01

    Full Text Available The paper systematically describes special regression methods – discrete choice models – known as probability models. The meaning of models and their methodological characteristics are described, as well as different types of models, especially binary-choice models and censored regression models. We considered three most commonly used approaches to estimating such models – logit, probit and tobit model.

  20. The ARCON modeling framework

    NARCIS (Netherlands)

    Afsarmanesh, H.; Camarinha-Matos, L.M.; Camarinha-Matos, L.M.; Afsarmanesh, H.

    2008-01-01

    A framework is defined for ARCON reference modeling, introducing multiple modeling perspectives of: Environment characteristics, life cycle stages, and modeling intents. This novel modeling framework takes into account contributions from previous related works, mainly on enterprise modeling, and

  1. Disease: H00063 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ia, brain stem, spinal cord (SCA3); cerebellum (SCA5); cerebellum, dentate nucleus, inferior olive... (SCA6); cerebellum, inferior olive, dentate nucleus, pontine nuclei (also the retina) (SCA...7); cerebral cortex, cerebellum (SCA12); cerebellum, inferior olive (SCA17) Microscopic lesion: neuronal inc

  2. Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study.

    Science.gov (United States)

    Dauriz, Marco; Porneala, Bianca C; Guo, Xiuqing; Bielak, Lawrence F; Peyser, Patricia A; Durant, Nefertiti H; Carnethon, Mercedes R; Bonadonna, Riccardo C; Bonora, Enzo; Bowden, Donald W; Florez, Jose C; Fornage, Myriam; Hivert, Marie-France; Jacobs, David R; Kabagambe, Edmond K; Lewis, Cora E; Murabito, Joanne M; Rasmussen-Torvik, Laura J; Rich, Stephen S; Vassy, Jason L; Yao, Jie; Carr, Jeffrey J; Kardia, Sharon L R; Siscovick, David; O'Donnell, Christopher J; Rotter, Jerome I; Dupuis, Josée; Meigs, James B

    2015-06-01

    Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. In a cross-sectional analysis, including ≤9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors-adjusted model (significance, PAtherosclerosis Europeans (fully-adjusted P=0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study (P=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults. SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci. © 2015 American Heart Association, Inc.

  3. Model Manipulation for End-User Modelers

    DEFF Research Database (Denmark)

    Acretoaie, Vlad

    , and proposes the VM* family of model manipulation languages addressing them. This family consists of the Visual Model Query Language (VMQL), the Visual Model Constraint Language (VMCL), and the Visual Model Transformation Language (VMTL). They allow modelers to specify and execute queries, constraints......End-user modelers are domain experts who create and use models as part of their work. They are typically not Software Engineers, and have little or no programming and meta-modeling experience. However, using model manipulation languages developed in the context of Model-Driven Engineering often...... integration, the VM* Runtime is deployed as a collection of lightweight Web Services. The claim that VM* languages offer end-user modelers superior learnability compared to existing model manipulation languages is verified empirically via user experiments complemented by qualitative evidence....

  4. The IMACLIM model; Le modele IMACLIM

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-07-01

    This document provides annexes to the IMACLIM model which propose an actualized description of IMACLIM, model allowing the design of an evaluation tool of the greenhouse gases reduction policies. The model is described in a version coupled with the POLES, technical and economical model of the energy industry. Notations, equations, sources, processing and specifications are proposed and detailed. (A.L.B.)

  5. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells

    Directory of Open Access Journals (Sweden)

    Ma Wei-Hsien

    2011-08-01

    Full Text Available Abstract Background Spinocerebellar ataxia (SCA refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model. Method Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain. Results Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice. Conclusion Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor

  6. Bank-based investing RoSCA for Islamic finance: a new alternative to drain households savings and reduce financial exclusion

    OpenAIRE

    BOUSALAM, Issam; HAMZAOUI, Moustapha

    2015-01-01

    On the arrival of the new banking law in Morocco, in august 2015, conventional banks and their foreign rivals will finally have the possibility to create their subsidiaries dedicated to microcredit, participative finance and payment, and hence, supply the market with new Islamic financial solutions for money saving and financing. In order to drain the substantial households savings escaping to classic banks, and consequently, gain ground among these latter, we think that those ...

  7. Prep1 (pKnox1 regulates mouse embryonic HSC cycling and self-renewal affecting the Stat1-Sca1 IFN-dependent pathway.

    Directory of Open Access Journals (Sweden)

    Livia Modica

    Full Text Available A hypomorphic Prep1 mutation results in embryonic lethality at late gestation with a pleiotropic embryonic phenotype that includes defects in all hematopoietic lineages. Reduced functionality of the hematopoietic stem cells (HSCs compartment might be responsible for the hematopoietic phenotype observed at mid-gestation. In this paper we demonstrate that Prep1 regulates the number of HSCs in fetal livers (FLs, their clonogenic potential and their ability to de novo generate the hematopoietic system in ablated hosts. Furthermore, we show that Prep1 controls the self-renewal ability of the FL HSC compartment as demonstrated by serial transplantation experiments. The premature exhaustion of Prep1 mutant HSCs correlates with the reduced quiescent stem cell pool thus suggesting that Prep1 regulates the self-renewal ability by controlling the quiescence/proliferation balance. Finally, we show that in FL HSCs Prep1 absence induces the interferon signaling pathway leading to premature cycling and exhaustion of fetal HSCs.

  8. Our De-Urbanized Cities and Other Obvious Paradoxes--An Outsider's Contributions to an Action Caucus of the SCA (Speech Communication Association).

    Science.gov (United States)

    Shaw, Eugene F.

    Despite large rural areas, the United States is basically an urban nation, particularly since the extensiveness and variety of communication networks, rather than open spaces, determine the true degree of urbanization of a region or community. A region is urban to the extent that its interpersonal and media channels are developed. The metropolitan…

  9. Two Distally Located Right SCA Aneurysms: Endovascular Treatment by Parent Artery Occlusion with GDC Coils and N-BCA Injection. Case Report and Review of the Literature.

    Science.gov (United States)

    Szajner, M; Obszaska, K; Nestorowicz, A; Szczerbo-Trojanowska, M

    2003-06-30

    Peripheral aneurysms of the superior cerebellar artery are considered difficult to treat surgically and endovascularly because of their inaccessibility. Parent artery occlusion is therefore frequently the preferred method. Embolic materials previously reported in this situation are either GDC coils or a polymerizing agent (n- BCA). We report a patient with two distally located, wide-neck aneurysms of the right superior cerebellar artery who presented with hemorrhage and was treated by endovascular embolization of the parent artery using a combination of GDC coils and n-BCA.

  10. Modelling live forensic acquisition

    CSIR Research Space (South Africa)

    Grobler, MM

    2009-06-01

    Full Text Available This paper discusses the development of a South African model for Live Forensic Acquisition - Liforac. The Liforac model is a comprehensive model that presents a range of aspects related to Live Forensic Acquisition. The model provides forensic...

  11. Concept Modeling vs. Data modeling in Practice

    DEFF Research Database (Denmark)

    Madsen, Bodil Nistrup; Erdman Thomsen, Hanne

    2015-01-01

    This chapter shows the usefulness of terminological concept modeling as a first step in data modeling. First, we introduce terminological concept modeling with terminological ontologies, i.e. concept systems enriched with characteristics modeled as feature specifications. This enables a formal...... account of the inheritance of characteristics and allows us to introduce a number of principles and constraints which render concept modeling more coherent than earlier approaches. Second, we explain how terminological ontologies can be used as the basis for developing conceptual and logical data models....... We also show how to map from the various elements in the terminological ontology to elements in the data models, and explain the differences between the models. Finally the usefulness of terminological ontologies as a prerequisite for IT development and data modeling is illustrated with examples from...

  12. Model-to-model interface for multiscale materials modeling

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Perry Edward [Iowa State Univ., Ames, IA (United States)

    2017-12-17

    A low-level model-to-model interface is presented that will enable independent models to be linked into an integrated system of models. The interface is based on a standard set of functions that contain appropriate export and import schemas that enable models to be linked with no changes to the models themselves. These ideas are presented in the context of a specific multiscale material problem that couples atomistic-based molecular dynamics calculations to continuum calculations of fluid ow. These simulations will be used to examine the influence of interactions of the fluid with an adjacent solid on the fluid ow. The interface will also be examined by adding it to an already existing modeling code, Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and comparing it with our own molecular dynamics code.

  13. Computational analysis of calcium signaling and membrane electrophysiology in cerebellar Purkinje neurons associated with ataxia

    Directory of Open Access Journals (Sweden)

    Brown Sherry-Ann

    2012-06-01

    Full Text Available Abstract Background Mutations in the smooth endoplasmic reticulum (sER calcium channel Inositol Trisphosphate Receptor type 1 (IP3R1 in humans with the motor function coordination disorders Spinocerebellar Ataxia Types 15 and 16 (SCA15/16 and in a corresponding mouse model, the IP3R1delta18/delta18 mice, lead to reduced IP3R1 levels. We posit that increasing IP3R1 sensitivity to IP3 in ataxias with reduced IP3R1 could restore normal calcium response. On the other hand, in mouse models of the human polyglutamine (polyQ ataxias, SCA2, and SCA3, the primary finding appears to be hyperactive IP3R1-mediated calcium release. It has been suggested that the polyQ SCA1 mice may also show hyperactive IP3R1. Yet, SCA1 mice show downregulated gene expression of IP3R1, Homer, metabotropic glutamate receptor (mGluR, smooth endoplasmic reticulum Ca-ATP-ase (SERCA, calbindin, parvalbumin, and other calcium signaling proteins. Results We create a computational model of pathological alterations in calcium signaling in cerebellar Purkinje neurons to investigate several forms of spinocerebellar ataxia associated with changes in the abundance, sensitivity, or activity of the calcium channel IP3R1. We find that increasing IP3R1 sensitivity to IP3 in computational models of SCA15/16 can restore normal calcium response if IP3R1 abundance is not too low. The studied range in IP3R1 levels reflects variability found in human and mouse ataxic models. Further, the required fold increases in sensitivity are within experimental ranges from experiments that use IP3R1 phosphorylation status to adjust its sensitivity to IP3. Results from our simulations of polyglutamine SCAs suggest that downregulation of some calcium signaling proteins may be partially compensatory. However, the downregulation of calcium buffer proteins observed in the SCA1 mice may contribute to pathology. Finally, our model suggests that the calcium-activated voltage-gated potassium channels may provide an

  14. Modeling cholera outbreaks

    Science.gov (United States)

    Longini, Ira M.; Morris, J. Glenn

    2014-01-01

    Mathematical modeling can be a valuable tool for studying infectious disease outbreak dynamics and simulating the effects of possible interventions. Here, we describe approaches to modeling cholera outbreaks and how models have been applied to explore intervention strategies, particularly in Haiti. Mathematical models can play an important role in formulating and evaluating complex cholera outbreak response options. Major challenges to cholera modeling are insufficient data for calibrating models and the need to tailor models for different outbreak scenarios. PMID:23412687

  15. Latent tree models

    OpenAIRE

    Zwiernik, Piotr

    2017-01-01

    Latent tree models are graphical models defined on trees, in which only a subset of variables is observed. They were first discussed by Judea Pearl as tree-decomposable distributions to generalise star-decomposable distributions such as the latent class model. Latent tree models, or their submodels, are widely used in: phylogenetic analysis, network tomography, computer vision, causal modeling, and data clustering. They also contain other well-known classes of models like hidden Markov models...

  16. Air Quality Dispersion Modeling - Alternative Models

    Science.gov (United States)

    Models, not listed in Appendix W, that can be used in regulatory applications with case-by-case justification to the Reviewing Authority as noted in Section 3.2, Use of Alternative Models, in Appendix W.

  17. Wake modelling combining mesoscale and microscale models

    DEFF Research Database (Denmark)

    Badger, Jake; Volker, Patrick; Prospathospoulos, J.

    2013-01-01

    In this paper the basis for introducing thrust information from microscale wake models into mesocale model wake parameterizations will be described. A classification system for the different types of mesoscale wake parameterizations is suggested and outlined. Four different mesoscale wake...

  18. Uncertainty Modeling Via Frequency Domain Model Validation

    Science.gov (United States)

    Waszak, Martin R.; Andrisani, Dominick, II

    1999-01-01

    Abstract The majority of literature on robust control assumes that a design model is available and that the uncertainty model bounds the actual variations about the nominal model. However, methods for generating accurate design models have not received as much attention in the literature. The influence of the level of accuracy of the uncertainty model on closed loop performance has received even less attention. The research reported herein is an initial step in applying and extending the concept of model validation to the problem of obtaining practical uncertainty models for robust control analysis and design applications. An extension of model validation called 'sequential validation' is presented and applied to a simple spring-mass-damper system to establish the feasibility of the approach and demonstrate the benefits of the new developments.

  19. From Numeric Models to Granular System Modeling

    OpenAIRE

    Pedrycz, Witold

    2015-01-01

    In the era of advanced methodologies and practices of system modeling, we are faced with ever growing challenges of building models of complex systems that are in full rapport with reality. These challenges are multifaceted. Human centricity becomes of paramount relevance in system modeling and because of this models need to be customized and easily interpretable. More and more visibly, experimental data and knowledge of varying quality being directly acquired from experts have to be efficien...

  20. A Model of Trusted Measurement Model

    OpenAIRE

    Ma Zhili; Wang Zhihao; Dai Liang; Zhu Xiaoqin

    2017-01-01

    A model of Trusted Measurement supporting behavior measurement based on trusted connection architecture (TCA) with three entities and three levels is proposed, and a frame to illustrate the model is given. The model synthesizes three trusted measurement dimensions including trusted identity, trusted status and trusted behavior, satisfies the essential requirements of trusted measurement, and unified the TCA with three entities and three levels.

  1. Molecular Models: Construction of Models with Magnets

    Directory of Open Access Journals (Sweden)

    Kalinovčić P.

    2015-07-01

    Full Text Available Molecular models are indispensable tools in teaching chemistry. Beside their high price, commercially available models are generally too small for classroom demonstration. This paper suggests how to make space-filling (callote models from Styrofoam with magnetic balls as connectors and disc magnets for showing molecular polarity

  2. Modelling binary data

    CERN Document Server

    Collett, David

    2002-01-01

    INTRODUCTION Some Examples The Scope of this Book Use of Statistical Software STATISTICAL INFERENCE FOR BINARY DATA The Binomial Distribution Inference about the Success Probability Comparison of Two Proportions Comparison of Two or More Proportions MODELS FOR BINARY AND BINOMIAL DATA Statistical Modelling Linear Models Methods of Estimation Fitting Linear Models to Binomial Data Models for Binomial Response Data The Linear Logistic Model Fitting the Linear Logistic Model to Binomial Data Goodness of Fit of a Linear Logistic Model Comparing Linear Logistic Models Linear Trend in Proportions Comparing Stimulus-Response Relationships Non-Convergence and Overfitting Some other Goodness of Fit Statistics Strategy for Model Selection Predicting a Binary Response Probability BIOASSAY AND SOME OTHER APPLICATIONS The Tolerance Distribution Estimating an Effective Dose Relative Potency Natural Response Non-Linear Logistic Regression Models Applications of the Complementary Log-Log Model MODEL CHECKING Definition of Re...

  3. ASME XI stroke time testing of solenoid valves at Connecticut Yankee Station

    Energy Technology Data Exchange (ETDEWEB)

    Martin, C.W.

    1996-12-01

    Connecticut Yankee Atomic Power Company has developed the capability of measuring the stroke times of AC and DC solenoid valves. This allows the station to measure the stroke time of any solenoid valve in the plant, even those valves which do not have valve stem position indicators. Connecticut Yankee has adapted the ITI MOVATS Checkmate 3 system, using a signal input from a Bruel and Kjaer (B&K) Model 4382 acoustic accelerometer and the Schaumberg Campbell Associates (SCA) Model SCA-1148 dual sensor, which is a combined accelerometer and gaussmeter.

  4. Modelling of Hydraulic Robot

    DEFF Research Database (Denmark)

    Madsen, Henrik; Zhou, Jianjun; Hansen, Lars Henrik

    1997-01-01

    This paper describes a case study of identifying the physical model (or the grey box model) of a hydraulic test robot. The obtained model is intended to provide a basis for model-based control of the robot. The physical model is formulated in continuous time and is derived by application...

  5. Elastic Appearance Models

    DEFF Research Database (Denmark)

    Hansen, Mads Fogtmann; Fagertun, Jens; Larsen, Rasmus

    2011-01-01

    This paper presents a fusion of the active appearance model (AAM) and the Riemannian elasticity framework which yields a non-linear shape model and a linear texture model – the active elastic appearance model (EAM). The non-linear elasticity shape model is more flexible than the usual linear...

  6. Modelling Foundations and Applications

    DEFF Research Database (Denmark)

    and selected from 81 submissions. Papers on all aspects of MDE were received, including topics such as architectural modelling and product lines, code generation, domain-specic modeling, metamodeling, model analysis and verication, model management, model transformation and simulation. The breadth of topics...

  7. Forest-fire models

    Science.gov (United States)

    Haiganoush Preisler; Alan Ager

    2013-01-01

    For applied mathematicians forest fire models refer mainly to a non-linear dynamic system often used to simulate spread of fire. For forest managers forest fire models may pertain to any of the three phases of fire management: prefire planning (fire risk models), fire suppression (fire behavior models), and postfire evaluation (fire effects and economic models). In...

  8. Numerical Modelling of Streams

    DEFF Research Database (Denmark)

    Vestergaard, Kristian

    In recent years there has been a sharp increase in the use of numerical water quality models. Numeric water quality modeling can be divided into three steps: Hydrodynamic modeling for the determination of stream flow and water levels. Modelling of transport and dispersion of a conservative dissol...... dissolved substance. Modeling of chemical and biological turnover of substances....

  9. "Bohr's Atomic Model."

    Science.gov (United States)

    Willden, Jeff

    2001-01-01

    "Bohr's Atomic Model" is a small interactive multimedia program that introduces the viewer to a simplified model of the atom. This interactive simulation lets students build an atom using an atomic construction set. The underlying design methodology for "Bohr's Atomic Model" is model-centered instruction, which means the central model of the…

  10. Model-Independent Diffs

    DEFF Research Database (Denmark)

    Könemann, Patrick

    just contain a list of strings, one for each line, whereas the structure of models is defined by their meta models. There are tools available which are able to compute the diff between two models, e.g. RSA or EMF Compare. However, their diff is not model-independent, i.e. it refers to the models...

  11. Dynamical cluster approximation plus semiclassical approximation study for a Mott insulator and d-wave pairing

    Science.gov (United States)

    Kim, SungKun; Lee, Hunpyo

    2017-06-01

    Via a dynamical cluster approximation with N c = 4 in combination with a semiclassical approximation (DCA+SCA), we study the doped two-dimensional Hubbard model. We obtain a plaquette antiferromagnetic (AF) Mott insulator, a plaquette AF ordered metal, a pseudogap (or d-wave superconductor) and a paramagnetic metal by tuning the doping concentration. These features are similar to the behaviors observed in copper-oxide superconductors and are in qualitative agreement with the results calculated by the cluster dynamical mean field theory with the continuous-time quantum Monte Carlo (CDMFT+CTQMC) approach. The results of our DCA+SCA differ from those of the CDMFT+CTQMC approach in that the d-wave superconducting order parameters are shown even in the high doped region, unlike the results of the CDMFT+CTQMC approach. We think that the strong plaquette AF orderings in the dynamical cluster approximation (DCA) with N c = 4 suppress superconducting states with increasing doping up to strongly doped region, because frozen dynamical fluctuations in a semiclassical approximation (SCA) approach are unable to destroy those orderings. Our calculation with short-range spatial fluctuations is initial research, because the SCA can manage long-range spatial fluctuations in feasible computational times beyond the CDMFT+CTQMC tool. We believe that our future DCA+SCA calculations should supply information on the fully momentum-resolved physical properties, which could be compared with the results measured by angle-resolved photoemission spectroscopy experiments.

  12. From Numeric Models to Granular System Modeling

    Directory of Open Access Journals (Sweden)

    Witold Pedrycz

    2015-03-01

    To make this study self-contained, we briefly recall the key concepts of granular computing and demonstrate how this conceptual framework and its algorithmic fundamentals give rise to granular models. We discuss several representative formal setups used in describing and processing information granules including fuzzy sets, rough sets, and interval calculus. Key architectures of models dwell upon relationships among information granules. We demonstrate how information granularity and its optimization can be regarded as an important design asset to be exploited in system modeling and giving rise to granular models. With this regard, an important category of rule-based models along with their granular enrichments is studied in detail.

  13. Modelling ECG signals with hidden Markov models.

    Science.gov (United States)

    Koski, A

    1996-10-01

    In this paper, we have studied the use of continuous probability density function hidden Markov models for the ECG signal analysis problem. Our previous work has focused on syntactic pattern recognition methods in signal processing. Hidden Markov model is basically a non-deterministic probabilistic finite state machine, which can be constructed inductively. It has been widely used in speech recognition and DNA modelling. We have found that hidden Markov models are very suitable for ECG recognition and analysis problems and that they are able to model accurately segmented ECG signals.

  14. Modeling regional wind erosion using different model

    Science.gov (United States)

    Guo, Zhongling; Chang, Chunping; Wang, Rende; Li, Jifeng; Li, Qing

    2017-04-01

    Wind erosion is an important factor causing soil degradation in arid and semi-arid regions. The need to quantitatively evaluate wind induced soil erosion yields many wind erosion models. These models include Wind Erosion Equation (WEQ), Revised Wind Erosion Equation (RWEQ),Wind Erosion Predicted System (WEPS) etc. at a field scale and Wind Erosion Assessment Model (WEAM), Integrated Wind Erosion Modeling System (IWEMS), AUStralian Land Erodibility Model (AUSLEM) etc. at a regional scale. The challenge of precisely estimating wind erosion at a regional scale still remain to date. To assess regional wind erosion, WEQ, RWEQ and WEPS have been scaled up to regional versions. However, no attempt is performed to compare these models for regional wind erosion modeling. In this study, the regional versions of WEQ, RWEQ, WEPS and WEAM, IWEMS, AUSLEM will be selected to model regional wind erosion of farmlands in the Kangbao County of northern China with annual soil loss by wind erosion based on 137 Cs analysis. Remote sensing image is used to determine the size and shape of local farmlands. Weather data of 2000-2010, China Soil Survey and published soil data, crops rotations etc. are compiled to generate raster layers of inputs for selected models using ArcGIS 10.2. These models were rebuilt based on ArcGIS Model-builder Module. Spatial distribution of annual soil loss by wind erosion determined from different model will be tested using annual soil loss data by 137 Cs analysis. Performances of these models will be investigated, and restrictions of these models will be further ascertained.

  15. Geologic Framework Model Analysis Model Report

    Energy Technology Data Exchange (ETDEWEB)

    R. Clayton

    2000-12-19

    The purpose of this report is to document the Geologic Framework Model (GFM), Version 3.1 (GFM3.1) with regard to data input, modeling methods, assumptions, uncertainties, limitations, and validation of the model results, qualification status of the model, and the differences between Version 3.1 and previous versions. The GFM represents a three-dimensional interpretation of the stratigraphy and structural features of the location of the potential Yucca Mountain radioactive waste repository. The GFM encompasses an area of 65 square miles (170 square kilometers) and a volume of 185 cubic miles (771 cubic kilometers). The boundaries of the GFM were chosen to encompass the most widely distributed set of exploratory boreholes (the Water Table or WT series) and to provide a geologic framework over the area of interest for hydrologic flow and radionuclide transport modeling through the unsaturated zone (UZ). The depth of the model is constrained by the inferred depth of the Tertiary-Paleozoic unconformity. The GFM was constructed from geologic map and borehole data. Additional information from measured stratigraphy sections, gravity profiles, and seismic profiles was also considered. This interim change notice (ICN) was prepared in accordance with the Technical Work Plan for the Integrated Site Model Process Model Report Revision 01 (CRWMS M&O 2000). The constraints, caveats, and limitations associated with this model are discussed in the appropriate text sections that follow. The GFM is one component of the Integrated Site Model (ISM) (Figure l), which has been developed to provide a consistent volumetric portrayal of the rock layers, rock properties, and mineralogy of the Yucca Mountain site. The ISM consists of three components: (1) Geologic Framework Model (GFM); (2) Rock Properties Model (RPM); and (3) Mineralogic Model (MM). The ISM merges the detailed project stratigraphy into model stratigraphic units that are most useful for the primary downstream models and the

  16. Wildfire Risk Main Model

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — The model combines three modeled fire behavior parameters (rate of spread, flame length, crown fire potential) and one modeled ecological health measure (fire regime...

  17. Energy modelling software

    CSIR Research Space (South Africa)

    Osburn, L

    2010-01-01

    Full Text Available The construction industry has turned to energy modelling in order to assist them in reducing the amount of energy consumed by buildings. However, while the energy loads of buildings can be accurately modelled, energy models often under...

  18. Mathematical Modeling Using MATLAB

    National Research Council Canada - National Science Library

    Phillips, Donovan

    1998-01-01

    .... Mathematical Modeling Using MA MATLAB acts as a companion resource to A First Course in Mathematical Modeling with the goal of guiding the reader to a fuller understanding of the modeling process...

  19. Models of Magnetism.

    Science.gov (United States)

    Borges, A. Tarciso; Gilbert, John K.

    1998-01-01

    Investigates the mental models that people construct about magnetic phenomena. Involves students, physics teachers, engineers, and practitioners. Proposes five models following a progression from simple description to a field model. Contains 28 references. (DDR)

  20. Collaborative networks: Reference modeling

    NARCIS (Netherlands)

    Camarinha-Matos, L.M.; Afsarmanesh, H.

    2008-01-01

    Collaborative Networks: Reference Modeling works to establish a theoretical foundation for Collaborative Networks. Particular emphasis is put on modeling multiple facets of collaborative networks and establishing a comprehensive modeling framework that captures and structures diverse perspectives of

  1. N-Gram models

    OpenAIRE

    Hiemstra, Djoerd; Lui, Ling; Özsu, M. Tamer

    2017-01-01

    In language modeling, n-gram models are probabilistic models of text that use some limited amount of history, or word dependencies, where n refers to the number of words that participate in the dependence relation.

  2. Computational neurogenetic modeling

    CERN Document Server

    Benuskova, Lubica

    2010-01-01

    Computational Neurogenetic Modeling is a student text, introducing the scope and problems of a new scientific discipline - Computational Neurogenetic Modeling (CNGM). CNGM is concerned with the study and development of dynamic neuronal models for modeling brain functions with respect to genes and dynamic interactions between genes. These include neural network models and their integration with gene network models. This new area brings together knowledge from various scientific disciplines, such as computer and information science, neuroscience and cognitive science, genetics and molecular biol

  3. Computer Security Models

    Science.gov (United States)

    1984-09-01

    September 1984 MTR9S31 " J. K. Millen Computer Security C. M. Cerniglia Models * 0 Ne c - ¢- C. S• ~CONTRACT SPONSOR OUSDRE/C31 & ESO/ALEE...given in Section 5, in the form of questions and answers about security modeling. A glossary of terms used in the context of computer security is...model, so we will not be able to pursue it in this report. MODEL CHARACTERISTICS Computer security models are engineering models, giving them somewhat

  4. Understandings of 'Modelling'

    DEFF Research Database (Denmark)

    Andresen, Mette

    2007-01-01

    This paper meets the common critique of the teaching of non-authentic modelling in school mathematics. In the paper, non-authentic modelling is related to a change of view on the intentions of modelling from knowledge about applications of mathematical models to modelling for concept formation. Non......-authentic modelling is also linked with the potentials of exploration of ready-made models as a forerunner for more authentic modelling processes. The discussion includes analysis of an episode of students? work in the classroom, which serves to illustrate how concept formation may be linked to explorations of a non...

  5. Global Business Models

    DEFF Research Database (Denmark)

    Rask, Morten

    insight from the literature about business models, international product policy, international entry modes and globalization into a conceptual model of relevant design elements of global business models, enabling global business model innovation to deal with differences in a downstream perspective...... regarding the customer interface and in an upstream perspective regarding the supply infrastructure. The paper offers a coherent conceptual dynamic meta-model of global business model innovation. Students, scholars and managers within the field of international business can use this conceptualization...... to understand, to study, and to create global business model innovation. Managerial and research implications draw on the developed ideal type of global business model innovation....

  6. Environmental Modeling Center

    Data.gov (United States)

    Federal Laboratory Consortium — The Environmental Modeling Center provides the computational tools to perform geostatistical analysis, to model ground water and atmospheric releases for comparison...

  7. Overuse Injury Assessment Model

    National Research Council Canada - National Science Library

    Stuhmiller, James H; Shen, Weixin; Sih, Bryant

    2005-01-01

    .... Previously, we developed a preliminary model that predicted the stress fracture rate and used biomechanical modeling, nonlinear optimization for muscle force, and bone structural analysis to estimate...

  8. TRACKING CLIMATE MODELS

    Data.gov (United States)

    National Aeronautics and Space Administration — CLAIRE MONTELEONI*, GAVIN SCHMIDT, AND SHAILESH SAROHA* Climate models are complex mathematical models designed by meteorologists, geophysicists, and climate...

  9. Validated dynamic flow model

    DEFF Research Database (Denmark)

    Knudsen, Torben

    2011-01-01

    model structure suggested by University of Lund the WP4 leader. This particular model structure has the advantages that it fits better into the control design frame work used by WP3-4 compared to the model structures previously developed in WP2. The different model structures are first summarised....... Then issues dealing with optimal experimental design is considered. Finally the parameters are estimated in the chosen static and dynamic models and a validation is performed. Two of the static models, one of them the additive model, explains the data well. In case of dynamic models the suggested additive...... model turns out not to be useful for prediction of the flow. Moreover, standard Box Jenkins model structures and multiple output auto regressive models proves to be superior as they can give useful predictions of the flow....

  10. Product and Process Modelling

    DEFF Research Database (Denmark)

    Cameron, Ian T.; Gani, Rafiqul

    This book covers the area of product and process modelling via a case study approach. It addresses a wide range of modelling applications with emphasis on modelling methodology and the subsequent in-depth analysis of mathematical models to gain insight via structural aspects of the models....... These approaches are put into the context of life cycle modelling, where multiscale and multiform modelling is increasingly prevalent in the 21st century. The book commences with a discussion of modern product and process modelling theory and practice followed by a series of case studies drawn from a variety...... of process industries. The book builds on the extensive modelling experience of the authors, who have developed models for both research and industrial purposes. It complements existing books by the authors in the modelling area. Those areas include the traditional petroleum and petrochemical industries...

  11. ROCK PROPERTIES MODEL ANALYSIS MODEL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Clinton Lum

    2002-02-04

    The purpose of this Analysis and Model Report (AMR) is to document Rock Properties Model (RPM) 3.1 with regard to input data, model methods, assumptions, uncertainties and limitations of model results, and qualification status of the model. The report also documents the differences between the current and previous versions and validation of the model. The rock properties models are intended principally for use as input to numerical physical-process modeling, such as of ground-water flow and/or radionuclide transport. The constraints, caveats, and limitations associated with this model are discussed in the appropriate text sections that follow. This work was conducted in accordance with the following planning documents: WA-0344, ''3-D Rock Properties Modeling for FY 1998'' (SNL 1997, WA-0358), ''3-D Rock Properties Modeling for FY 1999'' (SNL 1999), and the technical development plan, Rock Properties Model Version 3.1, (CRWMS M&O 1999c). The Interim Change Notice (ICNs), ICN 02 and ICN 03, of this AMR were prepared as part of activities being conducted under the Technical Work Plan, TWP-NBS-GS-000003, ''Technical Work Plan for the Integrated Site Model, Process Model Report, Revision 01'' (CRWMS M&O 2000b). The purpose of ICN 03 is to record changes in data input status due to data qualification and verification activities. These work plans describe the scope, objectives, tasks, methodology, and implementing procedures for model construction. The constraints, caveats, and limitations associated with this model are discussed in the appropriate text sections that follow. The work scope for this activity consists of the following: (1) Conversion of the input data (laboratory measured porosity data, x-ray diffraction mineralogy, petrophysical calculations of bound water, and petrophysical calculations of porosity) for each borehole into stratigraphic coordinates; (2) Re-sampling and merging of data sets; (3

  12. A Model of Trusted Measurement Model

    Directory of Open Access Journals (Sweden)

    Ma Zhili

    2017-01-01

    Full Text Available A model of Trusted Measurement supporting behavior measurement based on trusted connection architecture (TCA with three entities and three levels is proposed, and a frame to illustrate the model is given. The model synthesizes three trusted measurement dimensions including trusted identity, trusted status and trusted behavior, satisfies the essential requirements of trusted measurement, and unified the TCA with three entities and three levels.

  13. Integrity modelling of tropospheric delay models

    Science.gov (United States)

    Rózsa, Szabolcs; Bastiaan Ober, Pieter; Mile, Máté; Ambrus, Bence; Juni, Ildikó

    2017-04-01

    The effect of the neutral atmosphere on signal propagation is routinely estimated by various tropospheric delay models in satellite navigation. Although numerous studies can be found in the literature investigating the accuracy of these models, for safety-of-life applications it is crucial to study and model the worst case performance of these models using very low recurrence frequencies. The main objective of the INTegrity of TROpospheric models (INTRO) project funded by the ESA PECS programme is to establish a model (or models) of the residual error of existing tropospheric delay models for safety-of-life applications. Such models are required to overbound rare tropospheric delays and should thus include the tails of the error distributions. Their use should lead to safe error bounds on the user position and should allow computation of protection levels for the horizontal and vertical position errors. The current tropospheric model from the RTCA SBAS Minimal Operational Standards has an associated residual error that equals 0.12 meters in the vertical direction. This value is derived by simply extrapolating the observed distribution of the residuals into the tail (where no data is present) and then taking the point where the cumulative distribution has an exceedance level would be 10-7.While the resulting standard deviation is much higher than the estimated standard variance that best fits the data (0.05 meters), it surely is conservative for most applications. In the context of the INTRO project some widely used and newly developed tropospheric delay models (e.g. RTCA MOPS, ESA GALTROPO and GPT2W) were tested using 16 years of daily ERA-INTERIM Reanalysis numerical weather model data and the raytracing technique. The results showed that the performance of some of the widely applied models have a clear seasonal dependency and it is also affected by a geographical position. In order to provide a more realistic, but still conservative estimation of the residual

  14. Objective Bayes model selection in probit models.

    Science.gov (United States)

    Leon-Novelo, Luis; Moreno, Elías; Casella, George

    2012-02-20

    We describe a new variable selection procedure for categorical responses where the candidate models are all probit regression models. The procedure uses objective intrinsic priors for the model parameters, which do not depend on tuning parameters, and ranks the models for the different subsets of covariates according to their model posterior probabilities. When the number of covariates is moderate or large, the number of potential models can be very large, and for those cases, we derive a new stochastic search algorithm that explores the potential sets of models driven by their model posterior probabilities. The algorithm allows the user to control the dimension of the candidate models and thus can handle situations when the number of covariates exceed the number of observations. We assess, through simulations, the performance of the procedure and apply the variable selector to a gene expression data set, where the response is whether a patient exhibits pneumonia. Software needed to run the procedures is available in the R package varselectIP. Copyright © 2011 John Wiley & Sons, Ltd.

  15. New 3D model for dynamics modeling

    Science.gov (United States)

    Perez, Alain

    1994-05-01

    The wrist articulation represents one of the most complex mechanical systems of the human body. It is composed of eight bones rolling and sliding along their surface and along the faces of the five metacarpals of the hand and the two bones of the arm. The wrist dynamics are however fundamental for the hand movement, but it is so complex that it still remains incompletely explored. This work is a part of a new concept of computer-assisted surgery, which consists in developing computer models to perfect surgery acts by predicting their consequences. The modeling of the wrist dynamics are based first on the static model of its bones in three dimensions. This 3D model must optimise the collision detection procedure which is the necessary step to estimate the physical contact constraints. As many other possible computer vision models do not fit with enough precision to this problem, a new 3D model has been developed thanks to the median axis of the digital distance map of the bones reconstructed volume. The collision detection procedure is then simplified for contacts are detected between spheres. The experiment of this original 3D dynamic model products realistic computer animation images of solids in contact. It is now necessary to detect ligaments on digital medical images and to model them in order to complete a wrist model.

  16. Better models are more effectively connected models

    Science.gov (United States)

    Nunes, João Pedro; Bielders, Charles; Darboux, Frederic; Fiener, Peter; Finger, David; Turnbull-Lloyd, Laura; Wainwright, John

    2016-04-01

    The concept of hydrologic and geomorphologic connectivity describes the processes and pathways which link sources (e.g. rainfall, snow and ice melt, springs, eroded areas and barren lands) to accumulation areas (e.g. foot slopes, streams, aquifers, reservoirs), and the spatial variations thereof. There are many examples of hydrological and sediment connectivity on a watershed scale; in consequence, a process-based understanding of connectivity is crucial to help managers understand their systems and adopt adequate measures for flood prevention, pollution mitigation and soil protection, among others. Modelling is often used as a tool to understand and predict fluxes within a catchment by complementing observations with model results. Catchment models should therefore be able to reproduce the linkages, and thus the connectivity of water and sediment fluxes within the systems under simulation. In modelling, a high level of spatial and temporal detail is desirable to ensure taking into account a maximum number of components, which then enables connectivity to emerge from the simulated structures and functions. However, computational constraints and, in many cases, lack of data prevent the representation of all relevant processes and spatial/temporal variability in most models. In most cases, therefore, the level of detail selected for modelling is too coarse to represent the system in a way in which connectivity can emerge; a problem which can be circumvented by representing fine-scale structures and processes within coarser scale models using a variety of approaches. This poster focuses on the results of ongoing discussions on modelling connectivity held during several workshops within COST Action Connecteur. It assesses the current state of the art of incorporating the concept of connectivity in hydrological and sediment models, as well as the attitudes of modellers towards this issue. The discussion will focus on the different approaches through which connectivity

  17. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H196.

    Science.gov (United States)

    Marthaler, Adele G; Schmid, Benjamin; Tubsuwan, Alisa; Poulsen, Ulla B; Engelbrecht, Alexander F; Mau-Holzmann, Ulrike A; Hyttel, Poul; Nielsen, Jørgen E; Nielsen, Troels T; Holst, Bjørn

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell (iPSC) lines of SCA2 patients in order to study a disease-specific phenotype. Here, we demonstrate the gene correction of the iPSC line H196 clone 7 where we have exchanged the expanded CAG repeat of the ATXN2 gene with the normal length found in healthy alleles. This gene corrected cell line will provide the ideal control to model SCA2 by iPSC technology. Copyright © 2015. Published by Elsevier B.V.

  18. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H271.

    Science.gov (United States)

    Marthaler, Adele G; Schmid, Benjamin; Tubsuwan, Alisa; Poulsen, Ulla B; Engelbrecht, Alexander F; Mau-Holzmann, Ulrike A; Hyttel, Poul; Nielsen, Jørgen E; Nielsen, Troels T; Holst, Bjørn

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell (iPSC) lines of SCA2 patients in order to study a disease-specific phenotype. Here, we demonstrate the gene correction of the iPSC line H271 clone 1 where we have exchanged the expanded CAG repeat of the ATXN2 gene with the normal length found in healthy alleles. This gene corrected cell line will provide the ideal control to model SCA2 by iPSC technology. Copyright © 2015. Published by Elsevier B.V.

  19. Generation of an isogenic, gene-corrected control cell line of the spinocerebellar ataxia type 2 patient-derived iPSC line H266.

    Science.gov (United States)

    Marthaler, Adele G; Tubsuwan, Alisa; Schmid, Benjamin; Poulsen, Ulla B; Engelbrecht, Alexander F; Mau-Holzmann, Ulrike A; Hyttel, Poul; Nielsen, Troels T; Nielsen, Jørgen E; Holst, Bjørn

    2016-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease primarily affecting the cerebellum. Very little is known about the molecular mechanisms underlying the disease and, to date, no cure or treatment is available. We have successfully generated bona fide induced pluripotent stem cell (iPSC) lines of SCA2 patients in order to study a disease-specific phenotype. Here, we demonstrate the gene correction of the iPSC line H266 clone 10 where we have exchanged the expanded CAG repeat of the ATXN2 gene with the normal length found in healthy alleles. This gene corrected cell line will provide the ideal control to model SCA2 by iPSC technology. Copyright © 2016. Published by Elsevier B.V.

  20. Biosphere Model Report

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Wu

    2003-07-16

    The purpose of this report is to document the biosphere model, the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), which describes radionuclide transport processes in the biosphere and associated human exposure that may arise as the result of radionuclide release from the geologic repository at Yucca Mountain. The biosphere model is one of the process models that support the Yucca Mountain Project (YMP) Total System Performance Assessment (TSPA) for the license application (LA), the TSPA-LA. The ERMYN model provides the capability of performing human radiation dose assessments. This report documents the biosphere model, which includes: (1) Describing the reference biosphere, human receptor, exposure scenarios, and primary radionuclides for each exposure scenario (Section 6.1); (2) Developing a biosphere conceptual model using site-specific features, events, and processes (FEPs), the reference biosphere, the human receptor, and assumptions (Section 6.2 and Section 6.3); (3) Building a mathematical model using the biosphere conceptual model and published biosphere models (Sections 6.4 and 6.5); (4) Summarizing input parameters for the mathematical model, including the uncertainty associated with input values (Section 6.6); (5) Identifying improvements in the ERMYN model compared with the model used in previous biosphere modeling (Section 6.7); (6) Constructing an ERMYN implementation tool (model) based on the biosphere mathematical model using GoldSim stochastic simulation software (Sections 6.8 and 6.9); (7) Verifying the ERMYN model by comparing output from the software with hand calculations to ensure that the GoldSim implementation is correct (Section 6.10); and (8) Validating the ERMYN model by corroborating it with published biosphere models; comparing conceptual models, mathematical models, and numerical results (Section 7).

  1. Biosphere Model Report

    Energy Technology Data Exchange (ETDEWEB)

    M. A. Wasiolek

    2003-10-27

    The purpose of this report is to document the biosphere model, the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), which describes radionuclide transport processes in the biosphere and associated human exposure that may arise as the result of radionuclide release from the geologic repository at Yucca Mountain. The biosphere model is one of the process models that support the Yucca Mountain Project (YMP) Total System Performance Assessment (TSPA) for the license application (LA), the TSPA-LA. The ERMYN model provides the capability of performing human radiation dose assessments. This report documents the biosphere model, which includes: (1) Describing the reference biosphere, human receptor, exposure scenarios, and primary radionuclides for each exposure scenario (Section 6.1); (2) Developing a biosphere conceptual model using site-specific features, events, and processes (FEPs), the reference biosphere, the human receptor, and assumptions (Section 6.2 and Section 6.3); (3) Building a mathematical model using the biosphere conceptual model and published biosphere models (Sections 6.4 and 6.5); (4) Summarizing input parameters for the mathematical model, including the uncertainty associated with input values (Section 6.6); (5) Identifying improvements in the ERMYN model compared with the model used in previous biosphere modeling (Section 6.7); (6) Constructing an ERMYN implementation tool (model) based on the biosphere mathematical model using GoldSim stochastic simulation software (Sections 6.8 and 6.9); (7) Verifying the ERMYN model by comparing output from the software with hand calculations to ensure that the GoldSim implementation is correct (Section 6.10); and (8) Validating the ERMYN model by corroborating it with published biosphere models; comparing conceptual models, mathematical models, and numerical results (Section 7).

  2. AIDS Epidemiological models

    Science.gov (United States)

    Rahmani, Fouad Lazhar

    2010-11-01

    The aim of this paper is to present mathematical modelling of the spread of infection in the context of the transmission of the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS). These models are based in part on the models suggested in the field of th AIDS mathematical modelling as reported by ISHAM [6].

  3. Comparing Active Vision Models

    NARCIS (Netherlands)

    Croon, G.C.H.E. de; Sprinkhuizen-Kuyper, I.G.; Postma, E.O.

    2009-01-01

    Active vision models can simplify visual tasks, provided that they can select sensible actions given incoming sensory inputs. Many active vision models have been proposed, but a comparative evaluation of these models is lacking. We present a comparison of active vision models from two different

  4. Multivariate GARCH models

    DEFF Research Database (Denmark)

    Silvennoinen, Annastiina; Teräsvirta, Timo

    This article contains a review of multivariate GARCH models. Most common GARCH models are presented and their properties considered. This also includes nonparametric and semiparametric models. Existing specification and misspecification tests are discussed. Finally, there is an empirical example...... in which several multivariate GARCH models are fitted to the same data set and the results compared....

  5. Generic Market Models

    NARCIS (Netherlands)

    R. Pietersz (Raoul); M. van Regenmortel

    2005-01-01

    textabstractCurrently, there are two market models for valuation and risk management of interest rate derivatives, the LIBOR and swap market models. In this paper, we introduce arbitrage-free constant maturity swap (CMS) market models and generic market models featuring forward rates that span

  6. Models of Counselling Centres.

    Science.gov (United States)

    Calgary Univ. (Alberta).

    University counseling centers usually follow one of a variety of themes or "models," although not in pure form. Perhaps the oldest is the vocational counseling model, which concentrates on helping students find suitable careers. In the psychotherapy model, most student concerns are seen for their personal content. Another model, student affairs…

  7. The Instrumental Model

    Science.gov (United States)

    Yeates, Devin Rodney

    2011-01-01

    The goal of this dissertation is to enable better predictive models by engaging raw experimental data through the Instrumental Model. The Instrumental Model captures the protocols and procedures of experimental data analysis. The approach is formalized by encoding the Instrumental Model in an XML record. Decoupling the raw experimental data from…

  8. Dynamic epistemic modelling

    NARCIS (Netherlands)

    D.J.N. van Eijck (Jan)

    2004-01-01

    textabstractThis paper introduces DEMO, a Dynamic Epistemic Modelling tool. DEMO llows modelling epistemic updates, graphical display of update results, graphical display of action models, formula evaluation in epistemic models, translation of dynamic epistemic formulas to PDL formulas, and so on.

  9. System equivalent model mixing

    NARCIS (Netherlands)

    Klaassen, Steven W.B.; van der Seijs, M.V.; de Klerk, D.

    2017-01-01

    This paper introduces SEMM: a method based on Frequency Based Substructuring (FBS) techniques that enables the construction of hybrid dynamic models. With System Equivalent Model Mixing (SEMM) frequency based models, either of numerical or experimental nature, can be mixed to form a hybrid model.

  10. Comparing active vision models

    NARCIS (Netherlands)

    Croon, G.C.H.E. de; Sprinkhuizen-Kuyper, I.G.; Postma, E.O.

    2009-01-01

    Active vision models can simplify visual tasks, provided that they can select sensible actions given incoming sensory inputs. Many active vision models have been proposed, but a comparative evaluation of these models is lacking. We present a comparison of active vision models from two different

  11. Deeper model endgame analysis

    OpenAIRE

    Andrist, R.B.; Haworth, G.McC.

    2005-01-01

    A reference model of Fallible Endgame Play has been implemented and exercised with the chess-engine WILHELM. Past experiments have demonstrated the value of the model and the robustness of decisions based on it: experiments agree well with a Markov Model theory. Here, the reference model is exercised on the well-known endgame KBBKN.

  12. A Model for Conversation

    DEFF Research Database (Denmark)

    Ayres, Phil

    2012-01-01

    This essay discusses models. It examines what models are, the roles models perform and suggests various intentions that underlie their construction and use. It discusses how models act as a conversational partner, and how they support various forms of conversation within the conversational activity...... of design. Three distinctions are drawn through which to develop this discussion of models in an architectural context. An examination of these distinctions serves to nuance particular characteristics and roles of models, the modelling activity itself and those engaged in it....

  13. Wastewater Treatment Models

    DEFF Research Database (Denmark)

    Gernaey, Krist; Sin, Gürkan

    2008-01-01

    The state-of-the-art level reached in modeling wastewater treatment plants (WWTPs) is reported. For suspended growth systems, WWTP models have evolved from simple description of biological removal of organic carbon and nitrogen in aeration tanks (ASM1 in 1987) to more advanced levels including...... the practice of WWTP modeling by linking the wastewater treatment line with the sludge handling line in one modeling platform. Application of WWTP models is currently rather time consuming and thus expensive due to the high model complexity, and requires a great deal of process knowledge and modeling expertise...

  14. Wastewater treatment models

    DEFF Research Database (Denmark)

    Gernaey, Krist; Sin, Gürkan

    2011-01-01

    The state-of-the-art level reached in modeling wastewater treatment plants (WWTPs) is reported. For suspended growth systems, WWTP models have evolved from simple description of biological removal of organic carbon and nitrogen in aeration tanks (ASM1 in 1987) to more advanced levels including...... of WWTP modeling by linking the wastewater treatment line with the sludge handling line in one modeling platform. Application of WWTP models is currently rather time consuming and thus expensive due to the high model complexity, and requires a great deal of process knowledge and modeling expertise...

  15. Applied stochastic modelling

    CERN Document Server

    Morgan, Byron JT; Tanner, Martin Abba; Carlin, Bradley P

    2008-01-01

    Introduction and Examples Introduction Examples of data sets Basic Model Fitting Introduction Maximum-likelihood estimation for a geometric model Maximum-likelihood for the beta-geometric model Modelling polyspermy Which model? What is a model for? Mechanistic models Function Optimisation Introduction MATLAB: graphs and finite differences Deterministic search methods Stochastic search methods Accuracy and a hybrid approach Basic Likelihood ToolsIntroduction Estimating standard errors and correlations Looking at surfaces: profile log-likelihoods Confidence regions from profiles Hypothesis testing in model selectionScore and Wald tests Classical goodness of fit Model selection biasGeneral Principles Introduction Parameterisation Parameter redundancy Boundary estimates Regression and influence The EM algorithm Alternative methods of model fitting Non-regular problemsSimulation Techniques Introduction Simulating random variables Integral estimation Verification Monte Carlo inference Estimating sampling distributi...

  16. The Hospitable Meal Model

    DEFF Research Database (Denmark)

    Justesen, Lise; Overgaard, Svend Skafte

    2017-01-01

    This article presents an analytical model that aims to conceptualize how meal experiences are framed when taking into account a dynamic understanding of hospitality: the meal model is named The Hospitable Meal Model. The idea behind The Hospitable Meal Model is to present a conceptual model...... that can serve as a frame for developing hospitable meal competencies among professionals working within the area of institutional foodservices as well as a conceptual model for analysing meal experiences. The Hospitable Meal Model transcends and transforms existing meal models by presenting a more open......-ended approach towards meal experiences. The underlying purpose of The Hospitable Meal Model is to provide the basis for creating value for the individuals involved in institutional meal services. The Hospitable Meal Model was developed on the basis of an empirical study on hospital meal experiences explored...

  17. EMC Simulation and Modeling

    Science.gov (United States)

    Takahashi, Takehiro; Schibuya, Noboru

    The EMC simulation is now widely used in design stage of electronic equipment to reduce electromagnetic noise. As the calculated electromagnetic behaviors of the EMC simulator depends on the inputted EMC model of the equipment, the modeling technique is important to obtain effective results. In this paper, simple outline of the EMC simulator and EMC model are described. Some modeling techniques of EMC simulation are also described with an example of the EMC model which is shield box with aperture.

  18. Latent classification models

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre

    2005-01-01

    parametric family ofdistributions.  In this paper we propose a new set of models forclassification in continuous domains, termed latent classificationmodels. The latent classification model can roughly be seen ascombining the \\NB model with a mixture of factor analyzers,thereby relaxing the assumptions...... classification model, and wedemonstrate empirically that the accuracy of the proposed model issignificantly higher than the accuracy of other probabilisticclassifiers....

  19. Dynamical Dirichlet Mixture Model

    OpenAIRE

    Chen, Le; Barber, David; Odobez, Jean-Marc

    2007-01-01

    In this report, we propose a statistical model to deal with the discrete-distribution data varying over time. The proposed model -- HMM+DM -- extends the Dirichlet mixture model to the dynamic case: Hidden Markov Model with Dirichlet mixture output. Both the inference and parameter estimation procedures are proposed. Experiments on the generated data verify the proposed algorithms. Finally, we discuss the potential applications of the current model.

  20. Phenomenology of inflationary models

    Science.gov (United States)

    Olyaei, Abbas

    2018-01-01

    There are many inflationary models compatible with observational data. One can investigate inflationary models by looking at their general features, which are common in most of the models. Here we have investigated some of the single-field models without considering their origin in order to find the phenomenology of them. We have shown how to adjust the simple harmonic oscillator model in order to be in good agreement with observational data.

  1. Dimension of linear models

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar

    1996-01-01

    Determination of the proper dimension of a given linear model is one of the most important tasks in the applied modeling work. We consider here eight criteria that can be used to determine the dimension of the model, or equivalently, the number of components to use in the model. Four...... the basic problems in determining the dimension of linear models. Then each of the eight measures are treated. The results are illustrated by examples....

  2. Business Models and Business Model Innovation

    DEFF Research Database (Denmark)

    Foss, Nicolai J.; Saebi, Tina

    2017-01-01

    While research on business models and business model innovation continue to exhibit growth, the field is still, even after more than two decades of research, characterized by a striking lack of cumulative theorizing and an opportunistic borrowing of more or less related ideas from neighbouring...

  3. Modeling survival data extending the cox model

    CERN Document Server

    Therneau, Terry M

    2000-01-01

    Extending the Cox Model is aimed at researchers, practitioners, and graduate students who have some exposure to traditional methods of survival analysis The emphasis is on semiparametric methods based on the proportional hazards model The inclusion of examples with SAS and S-PLUS code will make the book accessible to most working statisticians

  4. Pavement Aging Model by Response Surface Modeling

    Directory of Open Access Journals (Sweden)

    Manzano-Ramírez A.

    2011-10-01

    Full Text Available In this work, surface course aging was modeled by Response Surface Methodology (RSM. The Marshall specimens were placed in a conventional oven for time and temperature conditions established on the basis of the environment factors of the region where the surface course is constructed by AC-20 from the Ing. Antonio M. Amor refinery. Volatilized material (VM, load resistance increment (ΔL and flow resistance increment (ΔF models were developed by the RSM. Cylindrical specimens with real aging were extracted from the surface course pilot to evaluate the error of the models. The VM model was adequate, in contrast (ΔL and (ΔF models were almost adequate with an error of 20 %, that was associated with the other environmental factors, which were not considered at the beginning of the research.

  5. Trapped Radiation Model Uncertainties: Model-Data and Model-Model Comparisons

    Science.gov (United States)

    Armstrong, T. W.; Colborn, B. L.

    2000-01-01

    The standard AP8 and AE8 models for predicting trapped proton and electron environments have been compared with several sets of flight data to evaluate model uncertainties. Model comparisons are made with flux and dose measurements made on various U.S. low-Earth orbit satellites (APEX, CRRES, DMSP, LDEF, NOAA) and Space Shuttle flights, on Russian satellites (Photon-8, Cosmos-1887, Cosmos-2044), and on the Russian Mir Space Station. This report gives the details of the model-data comparisons-summary results in terms of empirical model uncertainty factors that can be applied for spacecraft design applications are given in a combination report. The results of model-model comparisons are also presented from standard AP8 and AE8 model predictions compared with the European Space Agency versions of AP8 and AE8 and with Russian-trapped radiation models.

  6. The Model Confidence Set

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Nason, James M.

    acknowledges the limitations of the data, such that uninformative data yields a MCS with many models, whereas informative data yields a MCS with only a few models. The MCS procedure does not assume that a particular model is the true model, in fact theMCS procedure can be used to comparemore general objects......The paper introduces the model confidence set (MCS) and applies it to the selection of models. A MCS is a set of models that is constructed such that it will contain the best model with a given level of confidence. The MCS is in this sense analogous to a confidence interval for a parameter. The MCS......, beyond the comparison of models. We apply the MCS procedure to two empirical problems. First, we revisit the inflation forecasting problem posed by Stock and Watson (1999), and compute the MCS for their set of inflation forecasts. Second, we compare a number of Taylor rule regressions and determine...

  7. Practical Marginalized Multilevel Models

    Science.gov (United States)

    Griswold, Michael E.; Swihart, Bruce J.; Caffo, Brian S.; Zeger, Scott L.

    2013-01-01

    Clustered data analysis is characterized by the need to describe both systematic variation in a mean model and cluster-dependent random variation in an association model. Marginalized multilevel models embrace the robustness and interpretations of a marginal mean model, while retaining the likelihood inference capabilities and flexible dependence structures of a conditional association model. Although there has been increasing recognition of the attractiveness of marginalized multilevel models, there has been a gap in their practical application arising from a lack of readily available estimation procedures. We extend the marginalized multilevel model to allow for nonlinear functions in both the mean and association aspects. We then formulate marginal models through conditional specifications to facilitate estimation with mixed model computational solutions already in place. We illustrate the MMM and approximate MMM approaches on a cerebrovascular deficiency crossover trial using SAS and an epidemiological study on race and visual impairment using R. Datasets, SAS and R code are included as supplemental materials. PMID:24357884

  8. Product and Process Modelling

    DEFF Research Database (Denmark)

    Cameron, Ian T.; Gani, Rafiqul

    to biotechnology applications, food, polymer and human health application areas. The book highlights to important nature of modern product and process modelling in the decision making processes across the life cycle. As such it provides an important resource for students, researchers and industrial practitioners.......This book covers the area of product and process modelling via a case study approach. It addresses a wide range of modelling applications with emphasis on modelling methodology and the subsequent in-depth analysis of mathematical models to gain insight via structural aspects of the models....... These approaches are put into the context of life cycle modelling, where multiscale and multiform modelling is increasingly prevalent in the 21st century. The book commences with a discussion of modern product and process modelling theory and practice followed by a series of case studies drawn from a variety...

  9. Product and Process Modelling

    DEFF Research Database (Denmark)

    Cameron, Ian T.; Gani, Rafiqul

    This book covers the area of product and process modelling via a case study approach. It addresses a wide range of modelling applications with emphasis on modelling methodology and the subsequent in-depth analysis of mathematical models to gain insight via structural aspects of the models...... of process industries. The book builds on the extensive modelling experience of the authors, who have developed models for both research and industrial purposes. It complements existing books by the authors in the modelling area. Those areas include the traditional petroleum and petrochemical industries...... to biotechnology applications, food, polymer and human health application areas. The book highlights to important nature of modern product and process modelling in the decision making processes across the life cycle. As such it provides an important resource for students, researchers and industrial practitioners....

  10. Model Validation Status Review

    Energy Technology Data Exchange (ETDEWEB)

    E.L. Hardin

    2001-11-28

    The primary objective for the Model Validation Status Review was to perform a one-time evaluation of model validation associated with the analysis/model reports (AMRs) containing model input to total-system performance assessment (TSPA) for the Yucca Mountain site recommendation (SR). This review was performed in response to Corrective Action Request BSC-01-C-01 (Clark 2001, Krisha 2001) pursuant to Quality Assurance review findings of an adverse trend in model validation deficiency. The review findings in this report provide the following information which defines the extent of model validation deficiency and the corrective action needed: (1) AMRs that contain or support models are identified, and conversely, for each model the supporting documentation is identified. (2) The use for each model is determined based on whether the output is used directly for TSPA-SR, or for screening (exclusion) of features, events, and processes (FEPs), and the nature of the model output. (3) Two approaches are used to evaluate the extent to which the validation for each model is compliant with AP-3.10Q (Analyses and Models). The approaches differ in regard to whether model validation is achieved within individual AMRs as originally intended, or whether model validation could be readily achieved by incorporating information from other sources. (4) Recommendations are presented for changes to the AMRs, and additional model development activities or data collection, that will remedy model validation review findings, in support of licensing activities. The Model Validation Status Review emphasized those AMRs that support TSPA-SR (CRWMS M&O 2000bl and 2000bm). A series of workshops and teleconferences was held to discuss and integrate the review findings. The review encompassed 125 AMRs (Table 1) plus certain other supporting documents and data needed to assess model validity. The AMRs were grouped in 21 model areas representing the modeling of processes affecting the natural and

  11. Modeling volatility using state space models.

    Science.gov (United States)

    Timmer, J; Weigend, A S

    1997-08-01

    In time series problems, noise can be divided into two categories: dynamic noise which drives the process, and observational noise which is added in the measurement process, but does not influence future values of the system. In this framework, we show that empirical volatilities (the squared relative returns of prices) exhibit a significant amount of observational noise. To model and predict their time evolution adequately, we estimate state space models that explicitly include observational noise. We obtain relaxation times for shocks in the logarithm of volatility ranging from three weeks (for foreign exchange) to three to five months (for stock indices). In most cases, a two-dimensional hidden state is required to yield residuals that are consistent with white noise. We compare these results with ordinary autoregressive models (without a hidden state) and find that autoregressive models underestimate the relaxation times by about two orders of magnitude since they do not distinguish between observational and dynamic noise. This new interpretation of the dynamics of volatility in terms of relaxators in a state space model carries over to stochastic volatility models and to GARCH models, and is useful for several problems in finance, including risk management and the pricing of derivative securities. Data sets used: Olsen & Associates high frequency DEM/USD foreign exchange rates (8 years). Nikkei 225 index (40 years). Dow Jones Industrial Average (25 years).

  12. Model checking of healthcare domain models.

    Science.gov (United States)

    Baksi, Dibyendu

    2009-12-01

    This paper shows the application of a type of formal software verification technique known as lightweight model checking to a domain model in healthcare informatics in general and public health surveillance systems in particular. One of the most complex use cases of such a system is checked using assertions to verify one important system property. This use case is one of the major justifications for the complexity of the domain model. Alloy Analyzer verification tool is utilized for this purpose. Such verification work is very effective in either uncovering design flaws or in providing guarantees on certain desirable system properties in the earlier phases of the development lifecycle of any critical project.

  13. Modeling Guru: Knowledge Base for NASA Modelers

    Science.gov (United States)

    Seablom, M. S.; Wojcik, G. S.; van Aartsen, B. H.

    2009-05-01

    Modeling Guru is an on-line knowledge-sharing resource for anyone involved with or interested in NASA's scientific models or High End Computing (HEC) systems. Developed and maintained by the NASA's Software Integration and Visualization Office (SIVO) and the NASA Center for Computational Sciences (NCCS), Modeling Guru's combined forums and knowledge base for research and collaboration is becoming a repository for the accumulated expertise of NASA's scientific modeling and HEC communities. All NASA modelers and associates are encouraged to participate and provide knowledge about the models and systems so that other users may benefit from their experience. Modeling Guru is divided into a hierarchy of communities, each with its own set forums and knowledge base documents. Current modeling communities include those for space science, land and atmospheric dynamics, atmospheric chemistry, and oceanography. In addition, there are communities focused on NCCS systems, HEC tools and libraries, and programming and scripting languages. Anyone may view most of the content on Modeling Guru (available at http://modelingguru.nasa.gov/), but you must log in to post messages and subscribe to community postings. The site offers a full range of "Web 2.0" features, including discussion forums, "wiki" document generation, document uploading, RSS feeds, search tools, blogs, email notification, and "breadcrumb" links. A discussion (a.k.a. forum "thread") is used to post comments, solicit feedback, or ask questions. If marked as a question, SIVO will monitor the thread, and normally respond within a day. Discussions can include embedded images, tables, and formatting through the use of the Rich Text Editor. Also, the user can add "Tags" to their thread to facilitate later searches. The "knowledge base" is comprised of documents that are used to capture and share expertise with others. The default "wiki" document lets users edit within the browser so others can easily collaborate on the

  14. Empirical Model Building Data, Models, and Reality

    CERN Document Server

    Thompson, James R

    2011-01-01

    Praise for the First Edition "This...novel and highly stimulating book, which emphasizes solving real problems...should be widely read. It will have a positive and lasting effect on the teaching of modeling and statistics in general." - Short Book Reviews This new edition features developments and real-world examples that showcase essential empirical modeling techniques Successful empirical model building is founded on the relationship between data and approximate representations of the real systems that generated that data. As a result, it is essential for researchers who construct these m

  15. Wake Expansion Models

    DEFF Research Database (Denmark)

    Branlard, Emmanuel Simon Pierre

    2017-01-01

    Different models of wake expansion are presented in this chapter: the 1D momentum theory model, the cylinder analog model and Theodorsen’s model. Far wake models such as the ones from Frandsen or Rathmann or only briefly mentioned. The different models are compared to each other. Results from thi...... this chapter are used in Chap. 16 to link near-wake and far-wake parameters and in Chap. 20 to study the influence of expansion on tip-losses....

  16. Energy-consumption modelling

    Energy Technology Data Exchange (ETDEWEB)

    Reiter, E.R.

    1980-01-01

    A highly sophisticated and accurate approach is described to compute on an hourly or daily basis the energy consumption for space heating by individual buildings, urban sectors, and whole cities. The need for models and specifically weather-sensitive models, composite models, and space-heating models are discussed. Development of the Colorado State University Model, based on heat-transfer equations and on a heuristic, adaptive, self-organizing computation learning approach, is described. Results of modeling energy consumption by the city of Minneapolis and Cheyenne are given. Some data on energy consumption in individual buildings are included.

  17. Building Thermal Models

    Science.gov (United States)

    Peabody, Hume L.

    2017-01-01

    This presentation is meant to be an overview of the model building process It is based on typical techniques (Monte Carlo Ray Tracing for radiation exchange, Lumped Parameter, Finite Difference for thermal solution) used by the aerospace industry This is not intended to be a "How to Use ThermalDesktop" course. It is intended to be a "How to Build Thermal Models" course and the techniques will be demonstrated using the capabilities of ThermalDesktop (TD). Other codes may or may not have similar capabilities. The General Model Building Process can be broken into four top level steps: 1. Build Model; 2. Check Model; 3. Execute Model; 4. Verify Results.

  18. Program management model study

    Science.gov (United States)

    Connelly, J. J.; Russell, J. E.; Seline, J. R.; Sumner, N. R., Jr.

    1972-01-01

    Two models, a system performance model and a program assessment model, have been developed to assist NASA management in the evaluation of development alternatives for the Earth Observations Program. Two computer models were developed and demonstrated on the Goddard Space Flight Center Computer Facility. Procedures have been outlined to guide the user of the models through specific evaluation processes, and the preparation of inputs describing earth observation needs and earth observation technology. These models are intended to assist NASA in increasing the effectiveness of the overall Earth Observation Program by providing a broader view of system and program development alternatives.

  19. Microsoft tabular modeling cookbook

    CERN Document Server

    Braak, Paul te

    2013-01-01

    This book follows a cookbook style with recipes explaining the steps for developing analytic data using Business Intelligence Semantic Models.This book is designed for developers who wish to develop powerful and dynamic models for users as well as those who are responsible for the administration of models in corporate environments. It is also targeted at analysts and users of Excel who wish to advance their knowledge of Excel through the development of tabular models or who wish to analyze data through tabular modeling techniques. We assume no prior knowledge of tabular modeling

  20. Active registration models

    Science.gov (United States)

    Marstal, Kasper; Klein, Stefan

    2017-02-01

    We present the Active Registration Model (ARM) that couples medical image registration with regularization using a statistical model of intensity. Inspired by Active Appearance Models (AAMs), the statistical model is embedded in the registration procedure as a regularization term that penalize differences between a target image and a synthesized model reconstruction of that image. We demonstrate that the method generalizes AAMs to 3D images, many different transformation models, and many different gradient descent optimization methods. The method is validated on magnetic resonance images of human brains.

  1. SAM EMP (SEMP) model

    Energy Technology Data Exchange (ETDEWEB)

    Thatcher, R.M.

    1984-05-01

    The Surface-To-Air Missile (SAM) Electro-Magnetic-Pulse (EMP) (SEMP) model simulates the illumination of an entire SAM brigade with an EMP weapon. It computes probability distributions of SAM brigade performance levels after an EMP attack has occurred. Brigade performance is determined by the combination of components that survive the EMP. Accordingly, the SEMP model is separated into the component failure model and the condition model. The component failure model computes the failure probability of each component in the brigade from data supplied by two input data files. The condition model converts component failure probabilities into brigade performance in the form of missile availability probability tables.

  2. Holographic twin Higgs model.

    Science.gov (United States)

    Geller, Michael; Telem, Ofri

    2015-05-15

    We present the first realization of a "twin Higgs" model as a holographic composite Higgs model. Uniquely among composite Higgs models, the Higgs potential is protected by a new standard model (SM) singlet elementary "mirror" sector at the sigma model scale f and not by the composite states at m_{KK}, naturally allowing for m_{KK} beyond the LHC reach. As a result, naturalness in our model cannot be constrained by the LHC, but may be probed by precision Higgs measurements at future lepton colliders, and by direct searches for Kaluza-Klein excitations at a 100 TeV collider.

  3. Biosphere Model Report

    Energy Technology Data Exchange (ETDEWEB)

    D.W. Wu; A.J. Smith

    2004-11-08

    The purpose of this report is to document the biosphere model, the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), which describes radionuclide transport processes in the biosphere and associated human exposure that may arise as the result of radionuclide release from the geologic repository at Yucca Mountain. The biosphere model is one of the process models that support the Yucca Mountain Project (YMP) Total System Performance Assessment (TSPA) for the license application (LA), TSPA-LA. The ERMYN provides the capability of performing human radiation dose assessments. This report documents the biosphere model, which includes: (1) Describing the reference biosphere, human receptor, exposure scenarios, and primary radionuclides for each exposure scenario (Section 6.1); (2) Developing a biosphere conceptual model using site-specific features, events, and processes (FEPs) (Section 6.2), the reference biosphere (Section 6.1.1), the human receptor (Section 6.1.2), and approximations (Sections 6.3.1.4 and 6.3.2.4); (3) Building a mathematical model using the biosphere conceptual model (Section 6.3) and published biosphere models (Sections 6.4 and 6.5); (4) Summarizing input parameters for the mathematical model, including the uncertainty associated with input values (Section 6.6); (5) Identifying improvements in the ERMYN compared with the model used in previous biosphere modeling (Section 6.7); (6) Constructing an ERMYN implementation tool (model) based on the biosphere mathematical model using GoldSim stochastic simulation software (Sections 6.8 and 6.9); (7) Verifying the ERMYN by comparing output from the software with hand calculations to ensure that the GoldSim implementation is correct (Section 6.10); (8) Validating the ERMYN by corroborating it with published biosphere models; comparing conceptual models, mathematical models, and numerical results (Section 7).

  4. Modelling of Innovation Diffusion

    Directory of Open Access Journals (Sweden)

    Arkadiusz Kijek

    2010-01-01

    Full Text Available Since the publication of the Bass model in 1969, research on the modelling of the diffusion of innovation resulted in a vast body of scientific literature consisting of articles, books, and studies of real-world applications of this model. The main objective of the diffusion model is to describe a pattern of spread of innovation among potential adopters in terms of a mathematical function of time. This paper assesses the state-of-the-art in mathematical models of innovation diffusion and procedures for estimating their parameters. Moreover, theoretical issues related to the models presented are supplemented with empirical research. The purpose of the research is to explore the extent to which the diffusion of broadband Internet users in 29 OECD countries can be adequately described by three diffusion models, i.e. the Bass model, logistic model and dynamic model. The results of this research are ambiguous and do not indicate which model best describes the diffusion pattern of broadband Internet users but in terms of the results presented, in most cases the dynamic model is inappropriate for describing the diffusion pattern. Issues related to the further development of innovation diffusion models are discussed and some recommendations are given. (original abstract

  5. Model Checking CSL for Markov Population Models

    Directory of Open Access Journals (Sweden)

    David Spieler

    2014-06-01

    Full Text Available Markov population models (MPMs are a widely used modelling formalism in the area of computational biology and related areas. The semantics of a MPM is an infinite-state continuous-time Markov chain. In this paper, we use the established continuous stochastic logic (CSL to express properties of Markov population models. This allows us to express important measures of biological systems, such as probabilistic reachability, survivability, oscillations, switching times between attractor regions, and various others. Because of the infinite state space, available analysis techniques only apply to a very restricted subset of CSL properties. We present a full algorithm for model checking CSL for MPMs, and provide experimental evidence showing that our method is effective.

  6. Traffic & safety statewide model and GIS modeling.

    Science.gov (United States)

    2012-07-01

    Several steps have been taken over the past two years to advance the Utah Department of Transportation (UDOT) safety initiative. Previous research projects began the development of a hierarchical Bayesian model to analyze crashes on Utah roadways. De...

  7. Nonlinear Modeling by Assembling Piecewise Linear Models

    Science.gov (United States)

    Yao, Weigang; Liou, Meng-Sing

    2013-01-01

    To preserve nonlinearity of a full order system over a parameters range of interest, we propose a simple modeling approach by assembling a set of piecewise local solutions, including the first-order Taylor series terms expanded about some sampling states. The work by Rewienski and White inspired our use of piecewise linear local solutions. The assembly of these local approximations is accomplished by assigning nonlinear weights, through radial basis functions in this study. The efficacy of the proposed procedure is validated for a two-dimensional airfoil moving at different Mach numbers and pitching motions, under which the flow exhibits prominent nonlinear behaviors. All results confirm that our nonlinear model is accurate and stable for predicting not only aerodynamic forces but also detailed flowfields. Moreover, the model is robustness-accurate for inputs considerably different from the base trajectory in form and magnitude. This modeling preserves nonlinearity of the problems considered in a rather simple and accurate manner.

  8. Modelling freeway networks by hybrid stochastic models

    OpenAIRE

    Boel, R.; Mihaylova, L.

    2004-01-01

    Traffic flow on freeways is a nonlinear, many-particle phenomenon, with complex interactions between the vehicles. This paper presents a stochastic hybrid model of freeway traffic at a time scale and at a level of detail suitable for on-line flow estimation, for routing and ramp metering control. The model describes the evolution of continuous and discrete state variables. The freeway is considered as a network of components, each component representing a different section of the network. The...

  9. Laboratory of Biological Modeling

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to a...

  10. Modeling EERE deployment programs

    Energy Technology Data Exchange (ETDEWEB)

    Cort, K. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hostick, D. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Belzer, D. B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Livingston, O. V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2007-11-01

    The purpose of the project was to identify and characterize the modeling of deployment programs within the EERE Technology Development (TD) programs, address possible improvements to the modeling process, and note gaps in knowledge for future research.

  11. World Magnetic Model 2010

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The World Magnetic Model is the standard model used by the U.S. Department of Defense, the U.K. Ministry of Defence, the North Atlantic Treaty Organization (NATO)...

  12. Modeling of System Families

    National Research Council Canada - National Science Library

    Feiler, Peter

    2007-01-01

    .... The Society of Automotive Engineers (SAE) Architecture Analysis & Design Language (AADL) is an industry-standard, architecture-modeling notation specifically designed to support a component- based approach to modeling embedded systems...

  13. Graphical Models with R

    DEFF Research Database (Denmark)

    Højsgaard, Søren; Edwards, David; Lauritzen, Steffen L.

    Graphical models in their modern form have been around since the late 1970s and appear today in many areas of the sciences. Along with the ongoing developments of graphical models, a number of different graphical modeling software programs have been written over the years. In recent years many...... of these software developments have taken place within the R community, either in the form of new packages or by providing an R ingerface to existing software. This book attempts to give the reader a gentle introduction to graphical modeling using R and the main features of some of these packages. In addition......, the book provides examples of how more advanced aspects of graphical modeling can be represented and handled within R. Topics covered in the seven chapters include graphical models for contingency tables, Gaussian and mixed graphical models, Bayesian networks and modeling high dimensional data...

  14. Emissions Modeling Clearinghouse

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Emissions Modeling Clearinghouse (EMCH) supports and promotes emissions modeling activities both internal and external to the EPA. Through this site, the EPA...

  15. World Magnetic Model 2015

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The World Magnetic Model is the standard model used by the U.S. Department of Defense, the U.K. Ministry of Defence, the North Atlantic Treaty Organization (NATO)...

  16. Modelling Invoicing using SML

    DEFF Research Database (Denmark)

    Lichtenberg, Jakob; Hansen, Michael Reichhardt; Rischel, Hans

    1998-01-01

    This paper presents a solution to the Invoicing case study using the Standard ML programming language for modelling.......This paper presents a solution to the Invoicing case study using the Standard ML programming language for modelling....

  17. Modeling Philosophies and Applications

    Science.gov (United States)

    All models begin with a framework and a set of assumptions and limitations that go along with that framework. In terms of fracing and RA, there are several places where models and parameters must be chosen to complete hazard identification.

  18. ASC Champ Orbit Model

    DEFF Research Database (Denmark)

    Riis, Troels; Jørgensen, John Leif

    1999-01-01

    This documents describes a test of the implementation of the ASC orbit model for the Champ satellite.......This documents describes a test of the implementation of the ASC orbit model for the Champ satellite....

  19. Bounding Species Distribution Models

    Science.gov (United States)

    Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

  20. Modeling DNA Replication.

    Science.gov (United States)

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  1. Protein solubility modeling

    Science.gov (United States)

    Agena, S. M.; Pusey, M. L.; Bogle, I. D.

    1999-01-01

    A thermodynamic framework (UNIQUAC model with temperature dependent parameters) is applied to model the salt-induced protein crystallization equilibrium, i.e., protein solubility. The framework introduces a term for the solubility product describing protein transfer between the liquid and solid phase and a term for the solution behavior describing deviation from ideal solution. Protein solubility is modeled as a function of salt concentration and temperature for a four-component system consisting of a protein, pseudo solvent (water and buffer), cation, and anion (salt). Two different systems, lysozyme with sodium chloride and concanavalin A with ammonium sulfate, are investigated. Comparison of the modeled and experimental protein solubility data results in an average root mean square deviation of 5.8%, demonstrating that the model closely follows the experimental behavior. Model calculations and model parameters are reviewed to examine the model and protein crystallization process. Copyright 1999 John Wiley & Sons, Inc.

  2. The ATLAS Analysis Model

    CERN Multimedia

    Amir Farbin

    The ATLAS Analysis Model is a continually developing vision of how to reconcile physics analysis requirements with the ATLAS offline software and computing model constraints. In the past year this vision has influenced the evolution of the ATLAS Event Data Model, the Athena software framework, and physics analysis tools. These developments, along with the October Analysis Model Workshop and the planning for CSC analyses have led to a rapid refinement of the ATLAS Analysis Model in the past few months. This article introduces some of the relevant issues and presents the current vision of the future ATLAS Analysis Model. Event Data Model The ATLAS Event Data Model (EDM) consists of several levels of details, each targeted for a specific set of tasks. For example the Event Summary Data (ESD) stores calorimeter cells and tracking system hits thereby permitting many calibration and alignment tasks, but will be only accessible at particular computing sites with potentially large latency. In contrast, the Analysis...

  3. Model comparison in ANOVA.

    Science.gov (United States)

    Rouder, Jeffrey N; Engelhardt, Christopher R; McCabe, Simon; Morey, Richard D

    2016-12-01

    Analysis of variance (ANOVA), the workhorse analysis of experimental designs, consists of F-tests of main effects and interactions. Yet, testing, including traditional ANOVA, has been recently critiqued on a number of theoretical and practical grounds. In light of these critiques, model comparison and model selection serve as an attractive alternative. Model comparison differs from testing in that one can support a null or nested model vis-a-vis a more general alternative by penalizing more flexible models. We argue this ability to support more simple models allows for more nuanced theoretical conclusions than provided by traditional ANOVA F-tests. We provide a model comparison strategy and show how ANOVA models may be reparameterized to better address substantive questions in data analysis.

  4. Modeling Complex Time Limits

    Directory of Open Access Journals (Sweden)

    Oleg Svatos

    2013-01-01

    Full Text Available In this paper we analyze complexity of time limits we can find especially in regulated processes of public administration. First we review the most popular process modeling languages. There is defined an example scenario based on the current Czech legislature which is then captured in discussed process modeling languages. Analysis shows that the contemporary process modeling languages support capturing of the time limit only partially. This causes troubles to analysts and unnecessary complexity of the models. Upon unsatisfying results of the contemporary process modeling languages we analyze the complexity of the time limits in greater detail and outline lifecycles of a time limit using the multiple dynamic generalizations pattern. As an alternative to the popular process modeling languages there is presented PSD process modeling language, which supports the defined lifecycles of a time limit natively and therefore allows keeping the models simple and easy to understand.

  5. Snow model analysis.

    Science.gov (United States)

    2014-01-01

    This study developed a new snow model and a database which warehouses geometric, weather and traffic : data on New Jersey highways. The complexity of the model development lies in considering variable road : width, different spreading/plowing pattern...

  6. LAT Background Models

    Data.gov (United States)

    National Aeronautics and Space Administration — The Galactic model is a spatial and spectral template. The model for the Galactic diffuse emission was developed using spectral line surveys of HI and CO (as a...

  7. Modeling Touch and Palpation Using Autoregressive Models.

    Science.gov (United States)

    Laufer, Shlomi; Pugh, Carla; Van Veen, Barry D

    2017-05-05

    The human haptic system uses a set of reproducible and subconscious hand maneuvers to identify objects. Similar subconscious maneuvers are used during medical palpation for screening and diagnosis. The goal of this work was to develop a mathematical model that can be used to describe medical palpation techniques. Palpation data were measured using a two-dimensional array of force sensors. A novel algorithm for estimating the hand position from force data was developed. The hand position data were then modeled using multi-variate autoregressive models. Analysis of these models provided palpation direction and frequency as well as palpation type. The models were tested and validated using three different data sets: simulated data, a simplified experiment in which participant followed a known pattern and breast simulator palpation data. Simulated data showed that minimal error in estimating palpation direction and frequency is achieved when the sampling frequency is five to ten times the palpation frequency. The classification accuracy was 99% for the simplified experiment and 73% for the breast simulator data. Proper palpation is one of the vital components of many hands-on clinical examinations. In this study an algorithm for characterizing medical palpation was developed. The algorithm measured palpation frequency and direction for the first time and provided classification of palpation type. These newly developed models can be used for quantifying and assessing clinical technique and consequently lead to improved performance in palpation-based exams. Furthermore, they provide a general tool for the study of human haptics.

  8. Modelling pelagic biogeography

    Science.gov (United States)

    Olson, Donald B.; Hood, Raleigh R.

    Various combinations of physical and biological models are used to explore factors that determine the distribution of organisms in the world's oceans. The physical models examined include simple box models with parameterized inter-box exchanges that take into account variable box geometries, and specified continuous flows either in the Eulerian frame as stream-functions or as Lagrangian trajectories. A 1-dimensional mixed-layer model and a primitive equation channel model are introduced as examples of dynamical models depicting ocean physics. Biological models are discussed starting with a simple nitrogen (N), phytoplankton (P), zooplankton (Z) and detritus (D), NPZD formulation. The equilibria of this model is explored analytically as an example of computing steady state solutions, and then considering where in parameter space extinction occurs. Nonlinearities and expansion of NPZD to multi-species models are also treated. This is followed by the introduction of a nonlinear three-component food chain model, multi-species Lotka-Voltera competition models, and finally a discussion of structured population models including a derivation of a genetics model written in terms of genotypes. The physical models are then coupled with the biological ones in a series of examples. Both the box model with Lotka-Voltera multi-species population dynamics, and the 1-dimensional mixed-layer model with NPZD are used to demonstrate how the existence of spatial and temporal niches can allow a large number of species to coexist within biogeographic domains even though conditions at most sites and times are not conducive to supporting such diversity. These models recreate the basic diversity patterns observed in the pelagic ecosystem at various latitudes. The box model simulations also demonstrate the tendency for diffusive models to overestimate the dispersion of a species. In order to explore the dynamics of the edges of biogeographic domains a three species food chain model is

  9. Optimization modeling with spreadsheets

    CERN Document Server

    Baker, Kenneth R

    2015-01-01

    An accessible introduction to optimization analysis using spreadsheets Updated and revised, Optimization Modeling with Spreadsheets, Third Edition emphasizes model building skills in optimization analysis. By emphasizing both spreadsheet modeling and optimization tools in the freely available Microsoft® Office Excel® Solver, the book illustrates how to find solutions to real-world optimization problems without needing additional specialized software. The Third Edition includes many practical applications of optimization models as well as a systematic framework that il

  10. Photovoltaic sources modeling

    CERN Document Server

    Petrone, Giovanni; Spagnuolo, Giovanni

    2016-01-01

    This comprehensive guide surveys all available models for simulating a photovoltaic (PV) generator at different levels of granularity, from cell to system level, in uniform as well as in mismatched conditions. Providing a thorough comparison among the models, engineers have all the elements needed to choose the right PV array model for specific applications or environmental conditions matched with the model of the electronic circuit used to maximize the PV power production.

  11. Model Checking Feature Interactions

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Olsen, Petur; Pedersen, Thomas

    2015-01-01

    This paper presents an offline approach to analyzing feature interactions in embedded systems. The approach consists of a systematic process to gather the necessary information about system components and their models. The model is first specified in terms of predicates, before being refined to t...... to timed automata. The consistency of the model is verified at different development stages, and the correct linkage between the predicates and their semantic model is checked. The approach is illustrated on a use case from home automation....

  12. Artificial neural network modelling

    CERN Document Server

    Samarasinghe, Sandhya

    2016-01-01

    This book covers theoretical aspects as well as recent innovative applications of Artificial Neural networks (ANNs) in natural, environmental, biological, social, industrial and automated systems. It presents recent results of ANNs in modelling small, large and complex systems under three categories, namely, 1) Networks, Structure Optimisation, Robustness and Stochasticity 2) Advances in Modelling Biological and Environmental Systems and 3) Advances in Modelling Social and Economic Systems. The book aims at serving undergraduates, postgraduates and researchers in ANN computational modelling. .

  13. Modelling of Corrosion Cracks

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    Modelling of corrosion cracking of reinforced concrete structures is complicated as a great number of uncertain factors are involved. To get a reliable modelling a physical and mechanical understanding of the process behind corrosion in needed.......Modelling of corrosion cracking of reinforced concrete structures is complicated as a great number of uncertain factors are involved. To get a reliable modelling a physical and mechanical understanding of the process behind corrosion in needed....

  14. GARCH Modelling of Cryptocurrencies

    OpenAIRE

    Jeffrey Chu; Stephen Chan; Saralees Nadarajah; Joerg Osterrieder

    2017-01-01

    With the exception of Bitcoin, there appears to be little or no literature on GARCH modelling of cryptocurrencies. This paper provides the first GARCH modelling of the seven most popular cryptocurrencies. Twelve GARCH models are fitted to each cryptocurrency, and their fits are assessed in terms of five criteria. Conclusions are drawn on the best fitting models, forecasts and acceptability of value at risk estimates.

  15. Modelling Steel Behaviour

    OpenAIRE

    Anderberg, Yngve

    1986-01-01

    When modelling material mechanical behaviour, an analytical description is required of the relationship between stresses and strains. A computer oriented mechanical behaviour model for steel is described. The model is based on the fact that the deformation process at transient high temperature conditions can be desribed by three strain components which are separately found in different steady state tests. It is shown that a behaviour model based on steady state data satisfactorily predicts be...

  16. GARCH Modelling of Cryptocurrencies

    Directory of Open Access Journals (Sweden)

    Jeffrey Chu

    2017-10-01

    Full Text Available With the exception of Bitcoin, there appears to be little or no literature on GARCH modelling of cryptocurrencies. This paper provides the first GARCH modelling of the seven most popular cryptocurrencies. Twelve GARCH models are fitted to each cryptocurrency, and their fits are assessed in terms of five criteria. Conclusions are drawn on the best fitting models, forecasts and acceptability of value at risk estimates.

  17. Modeling anomalous superdiffusion

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, A [Institut fuer Physik, Technische Universitaet Chemnitz, D-09107 Chemnitz (Germany); Seeger, S [Institut fuer Physik, Technische Universitaet Chemnitz, D-09107 Chemnitz (Germany); Hoffmann, K H [Institut fuer Physik, Technische Universitaet Chemnitz, D-09107 Chemnitz (Germany); Essex, C [Department of Applied Mathematics, The University of Western Ontario, London N6A (Canada); Davison, M [Department of Applied Mathematics, The University of Western Ontario, London N6A (Canada)

    2007-09-21

    Continuous models for anomalous diffusion have previously been tested in the subdiffusive case by making comparisons to diffusion on a Sierpinski gasket. This paper extends this discussion to the superdiffusive case by comparing performance to diffusion on a tree model. Although there is reasonable agreement within limited regimes for all four models, one model, due to Compte and Jou, stands out as being consistently sound over all regimes studied.

  18. Validation of simulation models

    DEFF Research Database (Denmark)

    Rehman, Muniza; Pedersen, Stig Andur

    2012-01-01

    In philosophy of science, the interest for computational models and simulations has increased heavily during the past decades. Different positions regarding the validity of models have emerged but the views have not succeeded in capturing the diversity of validation methods. The wide variety...... of models has been somewhat narrow-minded reducing the notion of validation to establishment of truth. This article puts forward the diversity in applications of simulation models that demands a corresponding diversity in the notion of validation....

  19. Modelling Railway Interlocking Systems

    DEFF Research Database (Denmark)

    Lindegaard, Morten Peter; Viuf, P.; Haxthausen, Anne Elisabeth

    2000-01-01

    In this report we present a model of interlocking systems, and describe how the model may be validated by simulation. Station topologies are modelled by graphs in which the nodes denote track segments, and the edges denote connectivity for train traÆc. Points and signals are modelled by annotations...... on the edges, thereby restricting the driving possibilities. We de ne the safe station states as predicates on the graph, and present a rst step towards an implementation of these predicates....

  20. computer modeling ter modeling ter modeling of platinum reforming

    African Journals Online (AJOL)

    eobe

    Usually, the reformate that is leaving any stage o composition is assessed by laboratory analysis. The i which in most cases is avoided because of long comp hich in most cases is avoided because of long comp approach has considered a computer model as mean bed reactors in platforming u bed reactors in platforming ...

  1. Modelling agricultural production

    NARCIS (Netherlands)

    Wit, de C.T.

    1986-01-01

    In modelling in general and biological modelling in particular two approaches may be distinguished: a descriptive and an explanatory approach. In descriptive models the system and its behaviour are described at the same level at which the observations about it are made. A good example are the

  2. Business Model Innovation

    OpenAIRE

    Foss, Nicolai; Stieglitz, Nils

    2014-01-01

    We draw on the complementarity literature in economics and management research to dimensionalize business models innovations. Specifically, such innovation can be dimensionalized in terms of the depth and the breadth of the changes to the company’s business model that they imply. In turn, different business model innovations are associated with different management challenges and require different leadership interventions to become successful.

  3. Surface complexation modeling

    Science.gov (United States)

    Adsorption-desorption reactions are important processes that affect the transport of contaminants in the environment. Surface complexation models are chemical models that can account for the effects of variable chemical conditions, such as pH, on adsorption reactions. These models define specific ...

  4. Climate models and scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Fortelius, C.; Holopainen, E.; Kaurola, J.; Ruosteenoja, K.; Raeisaenen, J. [Helsinki Univ. (Finland). Dept. of Meteorology

    1996-12-31

    In recent years the modelling of interannual climate variability has been studied, the atmospheric energy and water cycles, and climate simulations with the ECHAM3 model. In addition, the climate simulations of several models have been compared with special emphasis in the area of northern Europe

  5. Linear Model Methodology

    CERN Document Server

    Khuri, Andre I

    2009-01-01

    Supported by a large number of examples, this book provides a foundation in the theory of linear models and explores the developments in data analysis. It encompasses a wide variety of topics in linear models that incorporate the classical approach and other trends and modeling techniques.

  6. Rock Properties Model

    Energy Technology Data Exchange (ETDEWEB)

    C. Lum

    2004-09-16

    The purpose of this model report is to document the Rock Properties Model version 3.1 with regard to input data, model methods, assumptions, uncertainties and limitations of model results, and qualification status of the model. The report also documents the differences between the current and previous versions and validation of the model. The rock properties model provides mean matrix and lithophysae porosity, and the cross-correlated mean bulk density as direct input to the ''Saturated Zone Flow and Transport Model Abstraction'', MDL-NBS-HS-000021, REV 02 (BSC 2004 [DIRS 170042]). The constraints, caveats, and limitations associated with this model are discussed in Section 6.6 and 8.2. Model validation accomplished by corroboration with data not cited as direct input is discussed in Section 7. The revision of this model report was performed as part of activities being conducted under the ''Technical Work Plan for: The Integrated Site Model, Revision 05'' (BSC 2004 [DIRS 169635]). The purpose of this revision is to bring the report up to current procedural requirements and address the Regulatory Integration Team evaluation comments. The work plan describes the scope, objectives, tasks, methodology, and procedures for this process.

  7. Model Breaking Points Conceptualized

    Science.gov (United States)

    Vig, Rozy; Murray, Eileen; Star, Jon R.

    2014-01-01

    Current curriculum initiatives (e.g., National Governors Association Center for Best Practices and Council of Chief State School Officers 2010) advocate that models be used in the mathematics classroom. However, despite their apparent promise, there comes a point when models break, a point in the mathematical problem space where the model cannot,…

  8. Symbol: artefact and model

    DEFF Research Database (Denmark)

    Galle, Per

    2000-01-01

    In preparation of an analysis of product modelling in terms of communication, this report presents a brief analysis of symbols; that is, the entities by means of which communication takes place. Symbols are defined in such a way as to admit artefacts and models (the latter including linguistic...... utterances as well as scale models) as special cases....

  9. Modeling Climate Dynamically

    Science.gov (United States)

    Walsh, Jim; McGehee, Richard

    2013-01-01

    A dynamical systems approach to energy balance models of climate is presented, focusing on low order, or conceptual, models. Included are global average and latitude-dependent, surface temperature models. The development and analysis of the differential equations and corresponding bifurcation diagrams provides a host of appropriate material for…

  10. A Model Performance

    Science.gov (United States)

    Thornton, Bradley D.; Smalley, Robert A.

    2008-01-01

    Building information modeling (BIM) uses three-dimensional modeling concepts, information technology and interoperable software to design, construct and operate a facility. However, BIM can be more than a tool for virtual modeling--it can provide schools with a 3-D walkthrough of a project while it still is on the electronic drawing board. BIM can…

  11. Subjects, Models, Languages, Transformations

    NARCIS (Netherlands)

    Rensink, Arend; Bézivin, J.; Heckel, R.

    2005-01-01

    Discussions about model-driven approaches tend to be hampered by terminological confusion. This is at least partially caused by a lack of formal precision in defining the basic concepts, including that of "model" and "thing being modelled" - which we call subject in this paper. We propose a minimal

  12. Modeling Natural Selection

    Science.gov (United States)

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  13. Modeling EERE Deployment Programs

    Energy Technology Data Exchange (ETDEWEB)

    Cort, K. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hostick, D. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Belzer, D. B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Livingston, O. V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2007-11-01

    This report compiles information and conclusions gathered as part of the “Modeling EERE Deployment Programs” project. The purpose of the project was to identify and characterize the modeling of deployment programs within the EERE Technology Development (TD) programs, address possible improvements to the modeling process, and note gaps in knowledge in which future research is needed.

  14. Modeling and Remodeling Writing

    Science.gov (United States)

    Hayes, John R.

    2012-01-01

    In Section 1 of this article, the author discusses the succession of models of adult writing that he and his colleagues have proposed from 1980 to the present. He notes the most important changes that differentiate earlier and later models and discusses reasons for the changes. In Section 2, he describes his recent efforts to model young…

  15. Bioeconomic and market models

    Science.gov (United States)

    Richard Haynes; Darius Adams; Peter Ince; John Mills; Ralph Alig

    2006-01-01

    The United States has a century of experience with the development of models that describe markets for forest products and trends in resource conditions. In the last four decades, increasing rigor in policy debates has stimulated the development of models to support policy analysis. Increasingly, research has evolved (often relying on computer-based models) to increase...

  16. Modeling Epidemic Network Failures

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Fagertun, Anna Manolova

    2013-01-01

    This paper presents the implementation of a failure propagation model for transport networks when multiple failures occur resulting in an epidemic. We model the Susceptible Infected Disabled (SID) epidemic model and validate it by comparing it to analytical solutions. Furthermore, we evaluate...

  17. Bayesian Graphical Models

    DEFF Research Database (Denmark)

    Jensen, Finn Verner; Nielsen, Thomas Dyhre

    2016-01-01

    Mathematically, a Bayesian graphical model is a compact representation of the joint probability distribution for a set of variables. The most frequently used type of Bayesian graphical models are Bayesian networks. The structural part of a Bayesian graphical model is a graph consisting of nodes...

  18. Urban tree growth modeling

    Science.gov (United States)

    E. Gregory McPherson; Paula J. Peper

    2012-01-01

    This paper describes three long-term tree growth studies conducted to evaluate tree performance because repeated measurements of the same trees produce critical data for growth model calibration and validation. Several empirical and process-based approaches to modeling tree growth are reviewed. Modeling is more advanced in the fields of forestry and...

  19. Hydrological land surface modelling

    DEFF Research Database (Denmark)

    Ridler, Marc-Etienne Francois

    and disaster management. The objective of this study is to develop and investigate methods to reduce hydrological model uncertainty by using supplementary data sources. The data is used either for model calibration or for model updating using data assimilation. Satellite estimates of soil moisture and surface...

  20. Dynamic term structure models

    DEFF Research Database (Denmark)

    Andreasen, Martin Møller; Meldrum, Andrew

    This paper studies whether dynamic term structure models for US nominal bond yields should enforce the zero lower bound by a quadratic policy rate or a shadow rate specification. We address the question by estimating quadratic term structure models (QTSMs) and shadow rate models with at most four...