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Sample records for suggests multiple functions

  1. Wide range of interacting partners of pea Gβ subunit of G-proteins suggests its multiple functions in cell signalling.

    Science.gov (United States)

    Bhardwaj, Deepak; Lakhanpaul, Suman; Tuteja, Narendra

    2012-09-01

    Climate change is a major concern especially in view of the increasing global population and food security. Plant scientists need to look for genetic tools whose appropriate usage can contribute to sustainable food availability. G-proteins have been identified as some of the potential genetic tools that could be useful for protecting plants from various stresses. Heterotrimeric G-proteins consisting of three subunits Gα, Gβ and Gγ are important components of a number of signalling pathways. Their structure and functions are already well studied in animals but their potential in plants is now gaining attention for their role in stress tolerance. Earlier we have reported that over expressing pea Gβ conferred heat tolerance in tobacco plants. Here we report the interacting partners (proteins) of Gβ subunit of Pisum sativum and their putative role in stress and development. Out of 90 transformants isolated from the yeast-two-hybrid (Y2H) screening, seven were chosen for further investigation due to their recurrence in multiple experiments. These interacting partners were confirmed using β-galactosidase colony filter lift and ONPG (O-nitrophenyl-β-D-galactopyranoside) assays. These partners include thioredoxin H, histidine-containing phosphotransfer protein 5-like, pathogenesis-related protein, glucan endo-beta-1, 3-glucosidase (acidic isoform), glycine rich RNA binding protein, cold and drought-regulated protein (corA gene) and soluble inorganic pyrophosphatase 1. This study suggests the role of pea Gβ subunit in stress signal transduction and development pathways owing to its capability to interact with a wide range of proteins of multiple functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

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    Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

    2012-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

  3. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

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    Claire S Leblond

    2012-02-01

    Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls. We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4% patients and in 16 of 1,090 (1.5% controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70. In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013. Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

  4. Suggestibility under Pressure: Theory of Mind, Executive Function, and Suggestibility in Preschoolers

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    Karpinski, Aryn C.; Scullin, Matthew H.

    2009-01-01

    Eighty preschoolers, ages 3 to 5 years old, completed a 4-phase study in which they experienced a live event and received a pressured, suggestive interview about the event a week later. Children were also administered batteries of theory of mind and executive function tasks, as well as the Video Suggestibility Scale for Children (VSSC), which…

  5. Structural and functional cerebral correlates of hypnotic suggestibility.

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    Alexa Huber

    Full Text Available Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

  6. Structural and functional cerebral correlates of hypnotic suggestibility.

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    Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

    2014-01-01

    Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

  7. Structural and functional correlates of hypnotic depth and suggestibility.

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    McGeown, William Jonathan; Mazzoni, Giuliana; Vannucci, Manila; Venneri, Annalena

    2015-02-28

    This study explores whether self-reported depth of hypnosis and hypnotic suggestibility are associated with individual differences in neuroanatomy and/or levels of functional connectivity. Twenty-nine people varying in suggestibility were recruited and underwent structural, and after a hypnotic induction, functional magnetic resonance imaging at rest. We used voxel-based morphometry to assess the correlation of grey matter (GM) and white matter (WM) against the independent variables: depth of hypnosis, level of relaxation and hypnotic suggestibility. Functional networks identified with independent components analysis were regressed with the independent variables. Hypnotic depth ratings were positively correlated with GM volume in the frontal cortex and the anterior cingulate cortex (ACC). Hypnotic suggestibility was positively correlated with GM volume in the left temporal-occipital cortex. Relaxation ratings did not correlate significantly with GM volume and none of the independent variables correlated with regional WM volume measures. Self-reported deeper levels of hypnosis were associated with less connectivity within the anterior default mode network. Taken together, the results suggest that the greater GM volume in the medial frontal cortex and ACC, and lower connectivity in the DMN during hypnosis facilitate experiences of greater hypnotic depth. The patterns of results suggest that hypnotic depth and hypnotic suggestibility should not be considered synonyms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Niche convergence suggests functionality of the nocturnal fovea.

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    Moritz, Gillian L; Melin, Amanda D; Tuh Yit Yu, Fred; Bernard, Henry; Ong, Perry S; Dominy, Nathaniel J

    2014-01-01

    The fovea is a declivity of the retinal surface associated with maximum visual acuity. Foveae are widespread across vertebrates, but among mammals they are restricted to haplorhine primates (tarsiers, monkeys, apes, and humans), which are primarily diurnal. Thus primates have long contributed to the view that foveae are functional adaptations to diurnality. The foveae of tarsiers, which are nocturnal, are widely interpreted as vestigial traits and therefore evidence of a diurnal ancestry. This enduring premise is central to adaptive hypotheses on the origins of anthropoid primates; however, the question of whether tarsier foveae are functionless anachronisms or nocturnal adaptations remains open. To explore this question, we compared the diets of tarsiers (Tarsius) and scops owls (Otus), taxa united by numerous anatomical homoplasies, including foveate vision. A functional interpretation of these homoplasies predicts dietary convergence. We tested this prediction by analyzing stable isotope ratios that integrate dietary information. In Borneo and the Philippines, the stable carbon isotope compositions of Tarsius and Otus were indistinguishable, whereas the stable nitrogen isotope composition of Otus was marginally higher than that of Tarsius. Our results indicate that species in both genera consumed mainly ground-dwelling prey. Taken together, our findings support a functional interpretation of the many homoplasies shared by tarsiers and scops owls, including a retinal fovea. We suggest that the fovea might function similarly in tarsiers and scops owls by calibrating the auditory localization pathway. The integration of auditory localization and visual fixation during prey detection and acquisition might be critical at low light levels.

  9. Ecologically relevant levels of multiple, common marine stressors suggest antagonistic effects.

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    Lange, Rolanda; Marshall, Dustin

    2017-07-24

    Stressors associated with global change will be experienced simultaneously and may act synergistically, so attempts to estimate the capacity of marine systems to cope with global change requires a multi-stressor approach. Because recent evidence suggests that stressor effects can be context-dependent, estimates of how stressors are experienced in ecologically realistic settings will be particularly valuable. To enhance our understanding of the interplay between environmental effects and the impact of multiple stressors from both natural and anthropogenic sources, we conducted a field experiment. We explored the impact of multiple, functionally varied stressors from both natural and anthropogenic sources experienced during early life history in a common sessile marine invertebrate, Bugula neritina. Natural spatial environmental variation induced differences in conspecific densities, allowing us to test for density-driven context-dependence of stressor effects. We indeed found density-dependent effects. Under high conspecific density, individual survival increased, which offset part of the negative effects of experiencing stressors. Experiencing multiple stressors early in life history translated to a decreased survival in the field, albeit the effects were not as drastic as we expected: our results are congruent with antagonistic stressor effects. We speculate that when individual stressors are more subtle, stressor synergies become less common.

  10. Unexpected Genome Variability at Multiple Loci Suggests Cacao Swollen Shoot Virus Comprises Multiple, Divergent Molecular Variants.

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    Cacao swollen shoot virus (CSSV) [Badnavirus, Caulimoviridae] causes swollen shoot disease of Theobroma cacao L. in West Africa. Since ~2000, various diagnostic tests have failed to detect CSSV in ~50-70% of symptomatic cacao plants, suggesting the possible emergence of new, previously uncharacteriz...

  11. Niche convergence suggests functionality of the nocturnal fovea

    Directory of Open Access Journals (Sweden)

    Gillian L. Moritz

    2014-07-01

    Full Text Available The fovea is a declivity of the retinal surface associated with maximum visual acuity. Foveae are widespread across vertebrates, but among mammals they are restricted to haplorhine primates (tarsiers, monkeys, apes, and humans, which are primarily diurnal. Thus primates have long contributed to the prevailing view that the fovea is a functional adaptation to diurnal color vision. The foveae of nocturnal taxa, such as tarsiers, are widely interpreted as vestigial traits and therefore evidence of a diurnal ancestry. This enduring premise has been central to adaptive hypotheses on the origins of anthropoid primates; however, the question of whether the fovea of tarsiers is a functionless anachronism or a nocturnal adaptation remains open. To address this question, we focused on the diets of tarsiers (Tarsius and scops owls (Otus, two taxa united by numerous anatomical homoplasies, including foveate vision. A functional interpretation of these homoplasies predicts dietary convergence and competition. This prediction can be tested with an analysis of carbon and nitrogen stable isotopes in tissues, which integrate dietary information. As predicted, the isotopic niches of Tarsius and Otus overlapped. In both Borneo and the Philippines, the δ13C values were indistinguishable, whereas the δ15N values of Otus were marginally higher than those of Tarsius. Our results indicate that both diets consisted mainly of ground-dwelling prey and raise the possibility of some resource partitioning. Taken together, our isotopic analysis supports a functional interpretation of the many homoplasies shared by tarsiers and scops owls, including a retinal fovea. We suggest that the fovea might function similarly in tarsiers and scops owls by calibrating the auditory localization pathway. The integration of auditory localization and visual fixation during prey detection and acquisition might be critical at low light levels.

  12. Time functions function best as functions of multiple times

    NARCIS (Netherlands)

    Desain, P.; Honing, H.

    1992-01-01

    This article presents an elegant way of representing control functions at an abstractlevel. It introduces time functions that have multiple times as arguments. In this waythe generalized concept of a time function can support absolute and relative kinds of time behavior. Furthermore the

  13. Functional Multiple-Set Canonical Correlation Analysis

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    Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

    2012-01-01

    We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

  14. Proteomic analysis of the Arabidopsis nucleolus suggests novel nucleolar functions

    DEFF Research Database (Denmark)

    Pendle, Alison F; Clark, Gillian P; Boon, Reinier

    2005-01-01

    The eukaryotic nucleolus is involved in ribosome biogenesis and a wide range of other RNA metabolism and cellular functions. An important step in the functional analysis of the nucleolus is to determine the complement of proteins of this nuclear compartment. Here, we describe the first proteomic ...

  15. Mitochondrial genome analyses suggest multiple Trichuris species in humans, baboons, and pigs from different geographical regions

    DEFF Research Database (Denmark)

    Hawash, Mohamed B. F.; Andersen, Lee O.; Gasser, Robin B.

    2015-01-01

    Trichuris from françois' leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related......) suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from......BACKGROUND: The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found...

  16. Genotyping of Burkholderia mallei from an outbreak of glanders in Bahrain suggests multiple introduction events.

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    Holger C Scholz

    2014-09-01

    Full Text Available Glanders, caused by the gram-negative bacterium Burkholderia mallei, is a highly infectious zoonotic disease of solipeds causing severe disease in animals and men. Although eradicated from many Western countries, it recently emerged in Asia, the Middle-East, Africa, and South America. Due to its rareness, little is known about outbreak dynamics of the disease and its epidemiology.We investigated a recent outbreak of glanders in Bahrain by applying high resolution genotyping (multiple locus variable number of tandem repeats, MLVA and comparative whole genome sequencing to B. mallei isolated from infected horses and a camel. These results were compared to samples obtained from an outbreak in the United Arab Emirates in 2004, and further placed into a broader phylogeographic context based on previously published B. mallei data. The samples from the outbreak in Bahrain separated into two distinct clusters, suggesting a complex epidemiological background and evidence for the involvement of multiple B. mallei strains. Additionally, the samples from Bahrain were more closely related to B. mallei isolated from horses in the United Arab Emirates in 2004 than other B. mallei which is suggestive of repeated importation to the region from similar geographic sources.High-resolution genotyping and comparative whole genome analysis revealed the same phylogenetic patterns among our samples. The close relationship of the Dubai/UAE B. mallei populations to each other may be indicative of a similar geographic origin that has yet to be identified for the infecting strains. The recent emergence of glanders in combination with worldwide horse trading might pose a new risk for human infections.

  17. Local functional connectivity suggests functional immaturity in children with attention-deficit/hyperactivity disorder.

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    Marcos-Vidal, Luis; Martínez-García, Magdalena; Pretus, Clara; Garcia-Garcia, David; Martínez, Kenia; Janssen, Joost; Vilarroya, Oscar; Castellanos, Francisco X; Desco, Manuel; Sepulcre, Jorge; Carmona, Susanna

    2018-06-01

    Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age. © 2018 Wiley Periodicals, Inc.

  18. Change in IgHV Mutational Status of CLL Suggests Origin From Multiple Clones.

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    Osman, Afaf; Gocke, Christopher D; Gladstone, Douglas E

    2017-02-01

    Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable. In a retrospective review, 409 CLL patients, between 2008 and 2015, had IgHV analysis: 56 patients had multiple analyses performed. Seven patients' IgHV results changed: 2 from unmutated to mutated and 5 from mutated to unmutated IgHV sequence. Three concurrently changed their variable heavy-chain sequence. Secondary to allelic exclusion, 2 of the new variable heavy chains produced were biologically nonplausible. The existence of these new nonplausible heavy-chain variable regions suggests either the CLL cancer stem-cell maintains the ability to rearrange a previously silenced IgH allele or more likely that the cancer stem-cell produced at least 2 subclones, suggesting that the CLL cancer stem cell exists before the process of allelic exclusion occurs. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Representations of Multiple-Valued Logic Functions

    CERN Document Server

    Stankovic, Radomir S

    2012-01-01

    Compared to binary switching functions, multiple-valued functions offer more compact representations of the information content of signals modeled by logic functions and, therefore, their use fits very well in the general settings of data compression attempts and approaches. The first task in dealing with such signals is to provide mathematical methods for their representation in a way that will make their application in practice feasible.Representation of Multiple-Valued Logic Functions is aimed at providing an accessible introduction to these mathematical techniques that are necessary for ap

  20. Child Abuse and Multiple Personality Disorders: Review of the Literature and Suggestions for Treatment.

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    Coons, Philip M.

    1986-01-01

    Multiple personality disorder is associated with a high incidence of physical and sexual abuse during childhood. While difficult to diagnose, multiple personality is easier to treat if diagnosed early in childhood or adolescence. Treatment for multiple personality focuses on establishing trust and communicating with and integrating the…

  1. Improving the characterization of radiologically isolated syndrome suggestive of multiple sclerosis.

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    Nicola De Stefano

    Full Text Available OBJECTIVE: To improve the characterization of asymptomatic subjects with brain magnetic resonance imaging (MRI abnormalities highly suggestive of multiple sclerosis (MS, a condition named as "radiologically isolated syndrome" (RIS. METHODS: Quantitative MRI metrics such as brain volumes and magnetization transfer (MT were assessed in 19 subjects previously classified as RIS, 20 demographically-matched relapsing-remitting MS (RRMS patients and 20 healthy controls (HC. Specific measures were: white matter (WM lesion volumes (LV, total and regional brain volumes, and MT ratio (MTr in lesions, normal-appearing WM (NAWM and cortex. RESULTS: LV was similar in RIS and RRMS, without differences in distribution and frequency at lesion mapping. Brain volumes were similarly lower in RRMS and RIS than in HC (p<0.001. Lesional-MTr was lower in RRMS than in RIS (p = 0.048; NAWM-MTr and cortical-MTr were similar in RIS and HC and lower (p<0.01 in RRMS. These values were particularly lower in RRMS than in RIS in the sensorimotor and memory networks. A multivariate logistic regression analysis showed that 13/19 RIS had ≥70% probability of being classified as RRMS on the basis of their brain volume and lesional-MTr values. CONCLUSIONS: Macroscopic brain damage was similar in RIS and RRMS. However, the subtle tissue damage detected by MTr was milder in RIS than in RRMS in clinically relevant brain regions, suggesting an explanation for the lack of clinical manifestations of subjects with RIS. This new approach could be useful for narrowing down the RIS individuals with a high risk of progression to MS.

  2. Clinically isolated syndromes suggestive of multiple sclerosis: an optical coherence tomography study.

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    Celia Oreja-Guevara

    Full Text Available BACKGROUND: Optical coherence tomography (OCT is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL, which provides an indirect measurement of axonal damage in multiple sclerosis (MS. This study aimed to evaluate RNFL thickness in patients at presentation with clinically isolated syndromes (CIS suggestive of MS. METHODOLOGY: This was a cross-sectional study. Twenty-four patients with CIS suggestive of MS (8 optic neuritis [ON], 6 spinal cord syndromes, 5 brainstem symptoms and 5 with sensory and other syndromes were prospectively studied. The main outcome evaluated was RNFL thickness at CIS onset. Secondary objectives were to study the relationship between RNFL thickness and MRI criteria for disease dissemination in space (DIS as well as the presence of oligoclonal bands in the cerebrospinal fluid. PRINCIPAL FINDINGS: Thirteen patients had decreased RNFL thickness in at least one quadrant. Mean RNFL thickness was 101.67±10.72 µm in retrobulbar ON eyes and 96.93±10.54 in unaffected eyes. Three of the 6 patients with myelitis had at least one abnormal quadrant in one of the two eyes. Eight CIS patients fulfilled DIS MRI criteria. The presence of at least one quadrant of an optic nerve with a RNFL thickness at a P<5% cut-off value had a sensitivity of 75% and a specificity of 56% for predicting DIS MRI. CONCLUSIONS: The findings from this study show that axonal damage measured by OCT is present in any type of CIS; even in myelitis forms, not only in ON as seen up to now. OCT can detect axonal damage in very early stages of disease and seems to have high sensitivity and moderate specificity for predicting DIS MRI. Studies with prospective long-term follow-up would be needed to establish the prognostic value of baseline OCT findings.

  3. Convergent Substitutions in a Sodium Channel Suggest Multiple Origins of Toxin Resistance in Poison Frogs.

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    Tarvin, Rebecca D; Santos, Juan C; O'Connell, Lauren A; Zakon, Harold H; Cannatella, David C

    2016-04-01

    Complex phenotypes typically have a correspondingly multifaceted genetic component. However, the genotype-phenotype association between chemical defense and resistance is often simple: genetic changes in the binding site of a toxin alter how it affects its target. Some toxic organisms, such as poison frogs (Anura: Dendrobatidae), have defensive alkaloids that disrupt the function of ion channels, proteins that are crucial for nerve and muscle activity. Using protein-docking models, we predict that three major classes of poison frog alkaloids (histrionicotoxins, pumiliotoxins, and batrachotoxins) bind to similar sites in the highly conserved inner pore of the muscle voltage-gated sodium channel, Nav1.4. We predict that poison frogs are somewhat resistant to these compounds because they have six types of amino acid replacements in the Nav1.4 inner pore that are absent in all other frogs except for a distantly related alkaloid-defended frog from Madagascar, Mantella aurantiaca. Protein-docking models and comparative phylogenetics support the role of these replacements in alkaloid resistance. Taking into account the four independent origins of chemical defense in Dendrobatidae, phylogenetic patterns of the amino acid replacements suggest that 1) alkaloid resistance in Nav1.4 evolved independently at least seven times in these frogs, 2) variation in resistance-conferring replacements is likely a result of differences in alkaloid exposure across species, and 3) functional constraint shapes the evolution of the Nav1.4 inner pore. Our study is the first to demonstrate the genetic basis of autoresistance in frogs with alkaloid defenses. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course

    DEFF Research Database (Denmark)

    Khademi, Mohsen; Kockum, Ingrid; Andersson, Magnus L

    2011-01-01

    Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments.......Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments....

  5. Student Strategies Suggesting Emergence of Mental Structures Supporting Logical and Abstract Thinking: Multiplicative Reasoning

    Science.gov (United States)

    Carrier, Jim

    2014-01-01

    For many students, developing mathematical reasoning can prove to be challenging. Such difficulty may be explained by a deficit in the core understanding of many arithmetical concepts taught in early school years. Multiplicative reasoning is one such concept that produces an essential foundation upon which higher-level mathematical thinking skills…

  6. The Role of Frontal Executive Functions in Hypnosis and Hypnotic Suggestibility

    OpenAIRE

    Parris, Benjamin

    2016-01-01

    There is both theoretical and empirical evidence supporting a role for frontal executive functions (FEFs) in hypnosis and hypnotic suggestibility. However, the precise nature of this involvement is debated. While there is clear evidence that FEFs are impaired under hypnosis, the cause of this decreased function is unclear. Theories make differing predictions as to the role of FEFs in hypnotic suggestibility, with some arguing that decreased baseline (normal function outside of the hypnotic co...

  7. Bayesian analyses of Yemeni mitochondrial genomes suggest multiple migration events with Africa and Western Eurasia.

    Science.gov (United States)

    Vyas, Deven N; Kitchen, Andrew; Miró-Herrans, Aida T; Pearson, Laurel N; Al-Meeri, Ali; Mulligan, Connie J

    2016-03-01

    Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation. We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades. As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a). Yemeni mitogenomes are largely the product of Holocene migration, and subsequent in situ evolution, from Africa and western Eurasia. However, we hypothesize that recent population movements may obscure the genetic signature of more ancient migrations. Additional research, e.g., analyses of Yemeni nuclear genetic data, is needed to better reconstruct the complex population and migration histories associated with Out of Africa. © 2015 Wiley Periodicals, Inc.

  8. Evidence for preserved novel word learning in Down syndrome suggests multiple routes to vocabulary acquisition.

    Science.gov (United States)

    Mosse, Emma K; Jarrold, Christopher

    2011-08-01

    Three studies investigated novel word learning, some requiring phonological production, each involving between 11 and 17 individuals with Down syndrome, and between 15 and 24 typically developing individuals matched for receptive vocabulary. The effect of stimuli wordlikeness and incidental procedure-based memory demands were examined to see whether these may account for an apparent impairment in word learning in Down syndrome demonstrated in earlier research. Paired associate word and nonword learning tasks were presented, requiring participants to learn the names of novel characters. The nonword stimuli varied in the degree of wordlikeness in 2 studies. A third study investigated extraneous task demand. Across 3 studies, there was no suggestion of a word learning deficit associated with Down syndrome (η(2)(p) for the main effect of group of .03, .11, and .03, respectively), despite the level of phonological representation required. There was evidence that novel word learning by participants with Down syndrome exceeded that which their verbal short-term memory capacity would predict. Vocabulary acquisition in Down syndrome may not rely on verbal short-term memory to the same extent as in typically developing children, lending support to the suggestion that new word learning may be underpinned by an additional memory process.

  9. Pulmonary function and dysfunction in multiple sclerosis.

    Science.gov (United States)

    Smeltzer, S C; Utell, M J; Rudick, R A; Herndon, R M

    1988-11-01

    Pulmonary function was studied in 25 patients with clinically definite multiple sclerosis with a range of motor impairment. Forced vital capacity (FVC), maximal voluntary ventilation (MVV), and maximal expiratory pressure (MEP) were normal in the ambulatory patients (mean greater than or equal to 80% predicted) but reduced in bedridden patients (mean, 38.5%, 31.6%, and 36.3% predicted; FCV, MVV, and MEP, respectively) and wheelchair-bound patients with upper extremity involvement (mean, 69.4%, 50.4%, and 62.6% predicted; FVC, MVV, and MEP, respectively). Forced vital capacity, MVV, and MEP correlated with Kurtzke Expanded Disability Status scores (tau = -0.72, -0.70, and -0.65) and expiratory muscle weakness occurred most frequently. These findings demonstrate that marked expiratory weakness develops in severely paraparetic patients with multiple sclerosis and the weakness increases as the upper extremities become increasingly involved.

  10. Differential frontal-parietal phase synchrony during hypnosis as a function of hypnotic suggestibility.

    Science.gov (United States)

    Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

    2011-10-01

    Spontaneous dissociative alterations in awareness and perception among highly suggestible individuals following a hypnotic induction may result from disruptions in the functional coordination of the frontal-parietal network. We recorded EEG and self-reported state dissociation in control and hypnosis conditions in two sessions with low and highly suggestible participants. Highly suggestible participants reliably experienced greater state dissociation and exhibited lower frontal-parietal phase synchrony in the alpha2 frequency band during hypnosis than low suggestible participants. These findings suggest that highly suggestible individuals exhibit a disruption of the frontal-parietal network that is only observable following a hypnotic induction. Copyright © 2011 Society for Psychophysiological Research.

  11. [Multiple sclerosis, loss of functionality and gender].

    Science.gov (United States)

    Bravo-González, Félix; Álvarez-Roldán, Arturo

    2017-12-01

    To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs. Interpretative-phenomenological qualitative study. Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme. The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology. Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. "Boom" and "Bust" cycles in virus growth suggest multiple selective forces in influenza a evolution

    Directory of Open Access Journals (Sweden)

    Marquart Mary E

    2011-04-01

    Full Text Available Abstract Background Influenza A virus evolution in humans is driven at least in part by mutations allowing the virus to escape antibody neutralization. Little is known about the evolution of influenza in birds, a major reservoir of influenza A. Methods Neutralizing polyclonal antiserum was raised in chicken against reassortant influenza virus, CalX, bearing the hemagglutinin (HA and neuraminidase (NA of A/California/7/2004 [H3N2]. CalX was serially passaged in the presence of anti-CalX polyclonal IgY to derive viruses capable of growth in the presence of antibody. Results Polyclonal chicken antibody neutralized both HA activity and infection by CalX, but had no effect on a strain bearing an earlier human H3 and an irrelevant neuraminidase (A/Memphis/71-Bellamy/42 [H3N1]. Surprisingly, most of the antibody-resistant viruses were still at least partially sensitive to neutralization of HA activity and viral infection. Although mutant HA genes bearing changes that might affect antibody neutralization were identified, the vast majority of HA sequences obtained were identical to wild type, and no individual mutant sequence was found in more than one passage, suggesting that those mutations that were observed did not confer sufficient selective advantage to come to dominate the population. Different passages yielded infectious foci of varying size and plaques of varying size and morphology. Yields of infectious virus and relative frequency of different morphologies changed markedly from passage to passage. Sequences of bulk, uncloned PCR products from antibody-resistant passages indicated changes in the PB2 and PA proteins with respect to the wild type virus. Conclusions Each antibody-selected passage consisted of a variety of different cocirculating populations, rather than pure populations of virus able to escape antibody by changes in antibody epitopes. The ability to escape antibody is apparently due to changes in genes encoding the viral

  13. Genotyping of human lice suggests multiple emergencies of body lice from local head louse populations.

    Directory of Open Access Journals (Sweden)

    Wenjun Li

    Full Text Available BACKGROUND: Genetic analyses of human lice have shown that the current taxonomic classification of head lice (Pediculus humanus capitis and body lice (Pediculus humanus humanus does not reflect their phylogenetic organization. Three phylotypes of head lice A, B and C exist but body lice have been observed only in phylotype A. Head and body lice have different behaviours and only the latter have been involved in outbreaks of infectious diseases including epidemic typhus, trench fever and louse borne recurrent fever. Recent studies suggest that body lice arose several times from head louse populations. METHODS AND FINDINGS: By introducing a new genotyping technique, sequencing variable intergenic spacers which were selected from louse genomic sequence, we were able to evaluate the genotypic distribution of 207 human lice. Sequence variation of two intergenic spacers, S2 and S5, discriminated the 207 lice into 148 genotypes and sequence variation of another two intergenic spacers, PM1 and PM2, discriminated 174 lice into 77 genotypes. Concatenation of the four intergenic spacers discriminated a panel of 97 lice into 96 genotypes. These intergenic spacer sequence types were relatively specific geographically, and enabled us to identify two clusters in France, one cluster in Central Africa (where a large body louse outbreak has been observed and one cluster in Russia. Interestingly, head and body lice were not genetically differentiated. CONCLUSIONS: We propose a hypothesis for the emergence of body lice, and suggest that humans with both low hygiene and head louse infestations provide an opportunity for head louse variants, able to ingest a larger blood meal (a required characteristic of body lice, to colonize clothing. If this hypothesis is ultimately supported, it would help to explain why poor human hygiene often coincides with outbreaks of body lice. Additionally, if head lice act as a reservoir for body lice, and that any social degradation in

  14. Profumo di SUSY: Suggestive Correlations in the ATLAS and CMS High Jet Multiplicity Data

    CERN Document Server

    Li, Tianjun; Nanopoulos, Dimitri V; Walker, Joel W

    2011-01-01

    We present persistently amassing evidence that the CMS and ATLAS Collaborations may indeed be already registering supersymmetry events at the Large Hadron Collider (LHC). Our analysis is performed in the context of a highly phenomenologically favorable model named No-Scale F-SU(5), which represents the unification of the F-lipped SU(5) Grand Unified Theory (GUT), two pairs of hypothetical TeV-scale vector-like supersymmetric multiplets derived out of F-Theory, and the dynamically established boundary conditions of No-Scale supergravity. We document highly suggestive correlations between the first inverse femtobarn of observations by CMS and ATLAS, where seductive excesses in multijet events, particularly those with nine or more jets, are unambiguously accounted for by a precision Monte-Carlo simulation of the F-SU(5) model space. This intimate correspondence is optimized by a unified gaugino mass in the neighborhood of M_{1/2}=518 GeV. We supplement this analysis by extrapolating for the expected data profile...

  15. Higher-order associative processing in Hermissenda suggests multiple sites of neuronal modulation.

    Science.gov (United States)

    Rogers, R F; Matzel, L D

    1996-01-01

    Two important features of modern accounts of associative learning are (1) the capacity for contextual stimuli to serve as a signal for an unconditioned stimulus (US) and (2) the capacity for a previously conditioned (excitatory) stimulus to "block" learning about a redundant stimulus when both stimuli serve as a signal for the same US. Here, we examined the process of blocking, thought by some to reflect a cognitive aspect of classical conditioning, and its underlying mechanisms in the marine mollusc Hermissenda. In two behavioral experiments, a context defined by chemosensory stimuli was made excitatory by presenting unsignalled USs (rotation) in that context. The excitatory context subsequently blocked overt learning about a discrete conditioned stimulus (CS; light) paired with the US in that context. In a third experiment, the excitability of the B photoreceptors in the Hermissenda eye, which typically increases following light-rotation pairings, was examined in behaviorally blocked animals, as well as in animals that had acquired a normal CS-US association or animals that had been exposed to the CS and US unpaired. Both the behaviorally blocked and the "normal" learning groups exhibited increases in neuronal excitability relative to unpaired animals. However, light-induced multiunit activity in pedal nerves was suppressed following normal conditioning but not in blocked or unpaired control animals, suggesting that the expression of blocking is mediated by neuronal modifications not directly reflected in B-cell excitability, possibly within an extensive network of central light-responsive interneurons.

  16. Genetic History of Xinjiang's Uyghurs Suggests Bronze Age Multiple-Way Contacts in Eurasia.

    Science.gov (United States)

    Feng, Qidi; Lu, Yan; Ni, Xumin; Yuan, Kai; Yang, Yajun; Yang, Xiong; Liu, Chang; Lou, Haiyi; Ning, Zhilin; Wang, Yuchen; Lu, Dongsheng; Zhang, Chao; Zhou, Ying; Shi, Meng; Tian, Lei; Wang, Xiaoji; Zhang, Xi; Li, Jing; Khan, Asifullah; Guan, Yaqun; Tang, Kun; Wang, Sijia; Xu, Shuhua

    2017-10-01

    The Uyghur people residing in Xinjiang, a territory located in the far west of China and crossed by the Silk Road, are a key ethnic group for understanding the history of human dispersion in Eurasia. Here we assessed the genetic structure and ancestry of 951 Xinjiang's Uyghurs (XJU) representing 14 geographical subpopulations. We observed a southwest and northeast differentiation within XJU, which was likely shaped jointly by the Tianshan Mountains, which traverses from east to west as a natural barrier, and gene flow from both east and west directions. In XJU, we identified four major ancestral components that were potentially derived from two earlier admixed groups: one from the West, harboring European (25-37%) and South Asian ancestries (12-20%), and the other from the East, with Siberian (15-17%) and East Asian (29-47%) ancestries. By using a newly developed method, MultiWaver, the complex admixture history of XJU was modeled as a two-wave admixture. An ancient wave was dated back to ∼3,750 years ago (ya), which is much earlier than that estimated by previous studies, but fits within the range of dating of mummies that exhibited European features that were discovered in the Tarim basin, which is situated in southern Xinjiang (4,000-2,000 ya); a more recent wave occurred around 750 ya, which is in agreement with the estimate from a recent study using other methods. We unveiled a more complex scenario of ancestral origins and admixture history in XJU than previously reported, which further suggests Bronze Age massive migrations in Eurasia and East-West contacts across the Silk Road. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

    Science.gov (United States)

    Tortorella, C; Romano, R; Direnzo, V; Taurisano, P; Zoccolella, S; Iaffaldano, P; Fazio, L; Viterbo, R; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

    2013-08-01

    Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

  18. On some recent suggestions of superluminal communication through the collapse of the wave function

    International Nuclear Information System (INIS)

    Ghirardi, G.C.; Weber, T.

    1979-01-01

    With reference to some recent suggestions of superluminal communication through the collapse of the wave function, it is proved that the suggested effects are derived using contradictory assumptions. Since the proof is based only on non-relativistic arguments, it is concluded that the difficulties connected with quantum measurement theory are only of conceptual nature. (author)

  19. Rapid genome reshaping by multiple-gene loss after whole-genome duplication in teleost fish suggested by mathematical modeling

    Science.gov (United States)

    Sato, Yukuto; Tsukamoto, Katsumi; Nishida, Mutsumi

    2015-01-01

    Whole-genome duplication (WGD) is believed to be a significant source of major evolutionary innovation. Redundant genes resulting from WGD are thought to be lost or acquire new functions. However, the rates of gene loss and thus temporal process of genome reshaping after WGD remain unclear. The WGD shared by all teleost fish, one-half of all jawed vertebrates, was more recent than the two ancient WGDs that occurred before the origin of jawed vertebrates, and thus lends itself to analysis of gene loss and genome reshaping. Using a newly developed orthology identification pipeline, we inferred the post–teleost-specific WGD evolutionary histories of 6,892 protein-coding genes from nine phylogenetically representative teleost genomes on a time-calibrated tree. We found that rapid gene loss did occur in the first 60 My, with a loss of more than 70–80% of duplicated genes, and produced similar genomic gene arrangements within teleosts in that relatively short time. Mathematical modeling suggests that rapid gene loss occurred mainly by events involving simultaneous loss of multiple genes. We found that the subsequent 250 My were characterized by slow and steady loss of individual genes. Our pipeline also identified about 1,100 shared single-copy genes that are inferred to have become singletons before the divergence of clupeocephalan teleosts. Therefore, our comparative genome analysis suggests that rapid gene loss just after the WGD reshaped teleost genomes before the major divergence, and provides a useful set of marker genes for future phylogenetic analysis. PMID:26578810

  20. Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

    Science.gov (United States)

    Miklós, István; Zádori, Zoltán

    2012-02-01

    HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (pHD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

  1. Altered thalamic functional connectivity in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou; Liang, Peipeng; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Jia, Xiuqin [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong, Huiqing; Ye, Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shi, Fu-Dong [Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2015-04-15

    Highlights: •We demonstrated decreased connectivity between thalamus and cortical regions in MS. •Increased intra- and inter-thalamic connectivity was also observed in MS. •The increased functional connectivity is attenuated by increasing disease duration. -- Abstract: Objective: To compare thalamic functional connectivity (FC) in patients with multiple sclerosis (MS) and healthy controls (HC), and correlate these connectivity measures with other MRI and clinical variables. Methods: We employed resting-state functional MRI (fMRI) to examine changes in thalamic connectivity by comparing thirty-five patients with MS and 35 age- and sex-matched HC. Thalamic FC was investigated by correlating low frequency fMRI signal fluctuations in thalamic voxels with voxels in all other brain regions. Additionally thalamic volume fraction (TF), T2 lesion volume (T2LV), EDSS and disease duration were recorded and correlated with the FC changes. Results: MS patients were found to have a significantly lower TF than HC in bilateral thalami. Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra- and inter-thalamic FC was observed in the MS group compared to HC. These FC alterations were not correlated with T2LV, thalamic volume or lesions. In the MS group, however, there was a negative correlation between disease duration and inter-thalamic connectivity (r = −0.59, p < 0.001). Conclusion: We demonstrated decreased FC between thalamus and several cortical regions, while increased intra- and inter-thalamic connectivity in MS patients. These complex functional changes reflect impairments and/or adaptations that are independent of T2LV, thalamic volume or presence of thalamic lesions. The negative correlation between disease duration and inter-thalamic connectivity could indicate an adaptive role of thalamus that is

  2. Event Memory and Suggestibility in Abused and Neglected Children: Trauma-Related Psychopathology and Cognitive Functioning

    Science.gov (United States)

    Chae, Yoojin; Goodman, Gail S.; Eisen, Mitchell L.; Qin, Jianjian

    2011-01-01

    This study examined event memory and suggestibility in 3- to 16-year-olds involved in forensic investigations of child maltreatment. A total of 322 children were interviewed about a play activity with an unfamiliar adult. Comprehensive measures of individual differences in trauma-related psychopathology and cognitive functioning were administered.…

  3. Ecosystem services capacity across heterogeneous forest types: understanding the interactions and suggesting pathways for sustaining multiple ecosystem services.

    Science.gov (United States)

    Alamgir, Mohammed; Turton, Stephen M; Macgregor, Colin J; Pert, Petina L

    2016-10-01

    As ecosystem services supply from tropical forests is declining due to deforestation and forest degradation, much effort is essential to sustain ecosystem services supply from tropical forested landscapes, because tropical forests provide the largest flow of multiple ecosystem services among the terrestrial ecosystems. In order to sustain multiple ecosystem services, understanding ecosystem services capacity across heterogeneous forest types and identifying certain ecosystem services that could be managed to leverage positive effects across the wider bundle of ecosystem services are required. We sampled three forest types, tropical rainforests, sclerophyll forests, and rehabilitated plantation forests, over an area of 32,000m(2) from Wet Tropics bioregion, Australia, aiming to compare supply and evaluate interactions and patterns of eight ecosystem services (global climate regulation, air quality regulation, erosion regulation, nutrient regulation, cyclone protection, habitat provision, energy provision, and timber provision). On average, multiple ecosystem services were highest in the rainforests, lowest in sclerophyll forests, and intermediate in rehabilitated plantation forests. However, a wide variation was apparent among the plots across the three forest types. Global climate regulation service had a synergistic impact on the supply of multiple ecosystem services, while nutrient regulation service was found to have a trade-off impact. Considering multiple ecosystem services, most of the rehabilitated plantation forest plots shared the same ordination space with rainforest plots in the ordination analysis, indicating that rehabilitated plantation forests may supply certain ecosystem services nearly equivalent to rainforests. Two synergy groups and one trade-off group were identified. Apart from conserving rainforests and sclerophyll forests, our findings suggest two additional integrated pathways to sustain the supply of multiple ecosystem services from a

  4. Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging

    Science.gov (United States)

    Ulrich, Martin; Kiefer, Markus; Bongartz, Walter; Grön, Georg; Hoenig, Klaus

    2015-01-01

    Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus) and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area). Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes. PMID:25923740

  5. Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Martin Ulrich

    Full Text Available Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area. Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes.

  6. Application of the ex-Gaussian function to the effect of the word blindness suggestion on Stroop task performance suggests no word blindness

    Directory of Open Access Journals (Sweden)

    Benjamin Andrew Parris

    2013-09-01

    Full Text Available The aim of the present paper was to apply the ex-Gaussian function to data reported by Parris et al. (2012 given its utility in studies involving the Stroop task. Parris et al. showed an effect of the word blindness suggestion when Response-Stimulus Interval (RSI was 500ms but not when it was 3500ms. Analysis revealed that: 1 The effect of the suggestion on interference is observed in µ, supporting converging evidence indicating the suggestion operates over response competition mechanisms; and, 2 Contrary to Parris et al., an effect of the suggestion was observed in µ when RSI was 3500ms. The reanalysis of the data from Parris et al. (2012 supports the utility of ex-Gaussian analysis in revealing effects that might otherwise be thought of as absent. We suggest that word reading itself is not suppressed by the suggestion but instead that response conflict is dealt with more effectively.

  7. Asymptotic functions and multiplication of distributions

    International Nuclear Information System (INIS)

    Todorov, T.D.

    1979-01-01

    Considered is a new type of generalized asymptotic functions, which are not functionals on some space of test functions as the Schwartz distributions. The definition of the generalized asymptotic functions is given. It is pointed out that in future the particular asymptotic functions will be used for solving some topics of quantum mechanics and quantum theory

  8. A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography.

    Science.gov (United States)

    Bunker, Richard D; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J; Pentelute, Bradley L; Lott, J Shaun; Kent, Stephen B H; Baker, Edward N

    2015-04-07

    Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the L- and D-enantiomeric forms of Rv1738 enabled facile crystallization of the D/L-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing L- and D-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis.

  9. Hypnotism as a Function of Trance State Effects, Expectancy, and Suggestibility: An Italian Replication.

    Science.gov (United States)

    Pekala, Ronald J; Baglio, Francesca; Cabinio, Monia; Lipari, Susanna; Baglio, Gisella; Mendozzi, Laura; Cecconi, Pietro; Pugnetti, Luigi; Sciaky, Riccardo

    2017-01-01

    Previous research using stepwise regression analyses found self-reported hypnotic depth (srHD) to be a function of suggestibility, trance state effects, and expectancy. This study sought to replicate and expand that research using a general state measure of hypnotic responsivity, the Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure (PCI-HAP). Ninety-five participants completed an Italian translation of the PCI-HAP, with srHD scores predicted from the PCI-HAP assessment items. The regression analysis replicated the previous research results. Additionally, stepwise regression analyses were able to predict the srHD score equally well using only the PCI dimension scores. These results not only replicated prior research but suggest how this methodology to assess hypnotic responsivity, when combined with more traditional neurophysiological and cognitive-behavioral methodologies, may allow for a more comprehensive understanding of that enigma called hypnosis.

  10. Patterns of genetic diversity of the cryptogenic red alga Polysiphonia morrowii (Ceramiales, Rhodophyta) suggest multiple origins of the Atlantic populations.

    Science.gov (United States)

    Geoffroy, Alexandre; Destombe, Christophe; Kim, Byeongseok; Mauger, Stéphane; Raffo, María Paula; Kim, Myung Sook; Le Gall, Line

    2016-08-01

    The red alga Polysiphonia morrowii, native to the North Pacific (Northeast Asia), has recently been reported worldwide. To determine the origin of the French and Argentine populations of this introduced species, we compared samples from these two areas with samples collected in Korea and at Hakodate, Japan, the type locality of the species. Combined analyses of chloroplastic (rbcL) and mitochondrial (cox1) DNA revealed that the French and Argentine populations are closely related and differ substantially from the Korean and Japanese populations. The genetic structure of P. morrowii populations from South Atlantic and North Atlantic, which showed high haplotype diversity compared with populations from the North Pacific, suggested the occurrence of multiple introduction events from areas outside of the so-called native regions. Although similar, the French and Argentine populations are not genetically identical. Thus, the genetic structure of these two introduced areas may have been modified by cryptic and recurrent introduction events directly from Asia or from other introduced areas that act as introduction relays. In addition, the large number of private cytoplasmic types identified in the two introduced regions strongly suggests that local populations of P. morrowii existed before the recent detection of these invasions. Our results suggest that the most likely scenario is that the source population(s) of the French and Argentine populations was not located only in the North Pacific and/or that P. morrowii is a cryptogenic species.

  11. COMPASS hadron multiplicity measurements and fragmentation functions

    International Nuclear Information System (INIS)

    Stolarski, M.

    2016-01-01

    COMPASS is an experiment located at CERN SPS accelerator. For the results presented in this paper a 160 GeV positive muon beam was impinging on 6 LiD target. The COMPASS spectrometer was designed to reconstruct scattered muons and charged hadrons in a wide kinematic range. COMPASS preliminary results on hadron, pion and kaon multiplicities are presented. The hadron and pion data show a good agreement with (N)LO QCD expectations and some of these preliminary data have been already successfully incorporated in the global NLO QCD fits to world data. However, the results for kaon multiplicities, are different from the expectations of the DSS fit. There is also a tension between COMPASS and HERMES results, the only other experiment which measured kaon multiplicities in Semi-Inclusive Deep Inelastic scattering

  12. Functional equation for the Mordell-Tornheim multiple zeta-function

    OpenAIRE

    Okamoto, Takuya; Onozuka, Tomokazu

    2016-01-01

    We show a relation between the Mordell-Tornheim multiple zeta-function and the confluent hypergeometric function, and using it, we give the functional equation for the Mordell-Tornheim multiple zeta-function. In the double case, the functional equation includes the known functional equation for the Euler-Zagier double zeta-function.

  13. Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway.

    Science.gov (United States)

    Medhurst, A L; Huber, P A; Waisfisz, Q; de Winter , J P; Mathew, C G

    2001-02-15

    Fanconi anaemia (FA) is an autosomal recessive inherited disorder associated with a progressive aplastic anaemia, diverse congenital abnormalities and cancer. The condition is genetically heterogeneous, with at least seven complementation groups (A-G) described. Cells from individuals who are homozygous for mutations in FA genes are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. These features suggest a possible role for the encoded proteins in the recognition or repair of these lesions, but neither their function nor whether they operate in a concerted or discrete functional pathways is known. The recent cloning of the FANCF and FANCE genes has allowed us to investigate the interaction of the proteins encoded by five of the seven complementation groups of FA. We used the yeast two-hybrid system and co-immunoprecipitation analysis to test the 10 possible pairs of proteins for direct interaction. In addition to the previously described binding of FANCA to FANCG, we now demonstrate direct interaction of FANCF with FANCG, of FANCC with FANCE and a weaker interaction of FANCE with both FANCA and FANCG. These findings show that the newly identified FANCE protein is an integral part of the FA pathway, and support the concept of a functional link between all known proteins encoded by the genes that are mutated in this disorder. These proteins may act either as a multimeric complex or by sequential recruitment of subsets of the proteins in a common pathway that protects the genomic integrity of mammalian cells.

  14. Small sets of interacting proteins suggest functional linkage mechanisms via Bayesian analogical reasoning.

    Science.gov (United States)

    Airoldi, Edoardo M; Heller, Katherine A; Silva, Ricardo

    2011-07-01

    Proteins and protein complexes coordinate their activity to execute cellular functions. In a number of experimental settings, including synthetic genetic arrays, genetic perturbations and RNAi screens, scientists identify a small set of protein interactions of interest. A working hypothesis is often that these interactions are the observable phenotypes of some functional process, which is not directly observable. Confirmatory analysis requires finding other pairs of proteins whose interaction may be additional phenotypical evidence about the same functional process. Extant methods for finding additional protein interactions rely heavily on the information in the newly identified set of interactions. For instance, these methods leverage the attributes of the individual proteins directly, in a supervised setting, in order to find relevant protein pairs. A small set of protein interactions provides a small sample to train parameters of prediction methods, thus leading to low confidence. We develop RBSets, a computational approach to ranking protein interactions rooted in analogical reasoning; that is, the ability to learn and generalize relations between objects. Our approach is tailored to situations where the training set of protein interactions is small, and leverages the attributes of the individual proteins indirectly, in a Bayesian ranking setting that is perhaps closest to propensity scoring in mathematical psychology. We find that RBSets leads to good performance in identifying additional interactions starting from a small evidence set of interacting proteins, for which an underlying biological logic in terms of functional processes and signaling pathways can be established with some confidence. Our approach is scalable and can be applied to large databases with minimal computational overhead. Our results suggest that analogical reasoning within a Bayesian ranking problem is a promising new approach for real-time biological discovery. Java code is available at

  15. The ubiquitous presence of exopolygalacturonase in maize suggests a fundamental cellular function for this enzyme.

    Science.gov (United States)

    Dubald, M; Barakate, A; Mandaron, P; Mache, R

    1993-11-01

    Exopolygalacturonase (exoPG) is a pectin-degrading enzyme abundant in maize pollen. Using immunochemistry and in situ hybridization it is shown that in addition to its presence in pollen, exoPG is also present in sporophytic tissues, such as the tapetum and mesophyll cells. The enzyme is located in the cytoplasm of pollen and of some mesophyll cells. In other mesophyll cells, the tapetum and the pollen tube, exoPG is located in the cell wall. The measurement of enzyme activity shows that exoPG is ubiquitous in the vegetative organs. These results suggest a general function for exoPG in cell wall edification or degradation. ExoPG is encoded by a closely related multigene family. The regulation of the expression of one of the exoPG genes was analyzed in transgenic tobacco. Reporter GUS activity was detected in anthers, seeds and stems but not in leaves or roots of transgenic plants. This strongly suggests that the ubiquitous presence of exoPG in maize is the result of the expression of different exoPG genes.

  16. A Switching Anti-windup Design Using Multiple Lyapunov Functions

    NARCIS (Netherlands)

    Lu, L.; Lin, Z.; Chen, J.

    2009-01-01

    This paper proposes a switching anti-windup design, which aims to enlarge the domain of attraction of the closed-loop system. Multiple anti-windup gains along with an index function that orchestrates the switching among these anti-windup gains are designed based on the min function of multiple

  17. The multiplicity function of galaxy systems

    International Nuclear Information System (INIS)

    Lucchin, F.

    1988-01-01

    The Press--Schechter approach to the mass function of cosmic structures is discussed by taking into account the effects of non-Guassian primordial perturbations and of the peak constraint, in the framework of the biased galaxy origin

  18. Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction.

    Directory of Open Access Journals (Sweden)

    Patrick S Mitchell

    2015-12-01

    Full Text Available Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host

  19. Suggestions for Layout and Functional Behavior of Software-Based Voice Switch Keysets

    Science.gov (United States)

    Scott, David W.

    2010-01-01

    Marshall Space Flight Center (MSFC) provides communication services for a number of real time environments, including Space Shuttle Propulsion support and International Space Station (ISS) payload operations. In such settings, control team members speak with each other via multiple voice circuits or loops. Each loop has a particular purpose and constituency, and users are assigned listen and/or talk capabilities for a given loop based on their role in fulfilling the purpose. A voice switch is a given facility's hardware and software that supports such communication, and may be interconnected with other facilities switches to create a large network that, from an end user perspective, acts like a single system. Since users typically monitor and/or respond to several voice loops concurrently for hours on end and real time operations can be very dynamic and intense, it s vital that a control panel or keyset for interfacing with the voice switch be a servant that reduces stress, not a master that adds it. Implementing the visual interface on a computer screen provides tremendous flexibility and configurability, but there s a very real risk of overcomplication. (Remember how office automation made life easier, which led to a deluge of documents that made life harder?) This paper a) discusses some basic human factors considerations related to keysets implemented as application software windows, b) suggests what to standardize at the facility level and what to leave to the user's preference, and c) provides screen shot mockups for a robust but reasonably simple user experience. Concepts apply to keyset needs in almost any type of operations control or support center.

  20. Molecular Diversity of Anthracnose Pathogen Populations Associated with UK Strawberry Production Suggests Multiple Introductions of Three Different Colletotrichum Species.

    Directory of Open Access Journals (Sweden)

    Riccardo Baroncelli

    Full Text Available Fragaria × ananassa (common name: strawberry is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l. is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production.

  1. Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from Maine, Minnesota, and Vermont suggest multiple etiologies

    Science.gov (United States)

    Meteyer, C.U.; Loeffler, I.K.; Fallon, J.F.; Converse, K.A.; Green, E.; Helgen, J.C.; Kersten, S.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

    2000-01-01

    Background Reports of malformed frogs have increased throughout the North American continent in recent years. Most of the observed malformations have involved the hind limbs. The goal of this study was to accurately characterize the hind limb malformations in wild frogs as an important step toward understanding the possible etiologies. Methods During 1997 and 1998, 182 recently metamorphosed northern leopard frogs (Rana pipiens) were collected from Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of these frogs, which underwent necropsy and radiographic evaluation at the National Wildlife Health Center. These malformations are described in detail and classified into four major categories: (1) no limb (amelia); (2) multiple limbs or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly; and (4) distally complete but malformed limb (bone rotations, bridging, skin webbing, and micromelia). Results Amelia and reduced segments and/or elements were the most common finding. Frogs with bilateral hind limb malformations were not common, and in only eight of these 22 frogs were the malformations symmetrical. Malformations of a given type tended to occur in frogs collected from the same site, but the types of malformations varied widely among all three states, and between study sites within Minnesota. Conclusions Clustering of malformation type suggests that developmental events may produce a variety of phenotypes depending on the timing, sequence, and severity of the environmental insult. Hind limb malformations in free-living frogs transcend current mechanistic explanations of tetrapod limb development.

  2. Molecular Diversity of Anthracnose Pathogen Populations Associated with UK Strawberry Production Suggests Multiple Introductions of Three Different Colletotrichum Species

    Science.gov (United States)

    Baroncelli, Riccardo; Zapparata, Antonio; Sarrocco, Sabrina; Sukno, Serenella A.; Lane, Charles R.; Thon, Michael R.; Vannacci, Giovanni; Holub, Eric; Sreenivasaprasad, Surapareddy

    2015-01-01

    Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production. PMID:26086351

  3. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    Science.gov (United States)

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    "rocker switch" may apply to certain MFS transporters, intermediate "tilted" states may exist under certain circumstances or as transitional structures. Although wet lab experimental confirmation is required, our results suggest that transport mechanisms in this transporter family should probably not be assumed to be conserved simply based on standard structural homology considerations. Furthermore, steered molecular dynamics elucidating energetic interactions of ligands with amino acid residues in an appropriately modeled transporter may have predictive value in understanding the impact of mutations and/or polymorphisms on transporter function.

  4. Nuclei of aged myofibres undergo structural and functional changes suggesting impairment in RNA processing

    Directory of Open Access Journals (Sweden)

    C Pellicciari

    2009-06-01

    Full Text Available Advancing adult age is associated with a progressive decrease in skeletal muscle mass, strength and quality known as sarcopenia. The mechanisms underlying age-related skeletal muscle wasting and weakness are manifold and still remain to be fully elucidated. Despite the increasing evidence that the progress of muscle diseases leading to muscle atrophy/dystrophy may be related to defective RNA processing, no data on the morpho-functional features of skeletal muscle nuclei in sarcopenia are available at present. In this view, we have investigated, by combining morphometry and immunocytochemistry at light and electron microscopy, the fine structure of myonuclei as well as the distribution and amount of RNA processing factors in skeletal myofibres of biceps brachii and quadriceps femoris from adult and old rats. Results demonstrate that the myonuclei of aged type II fibres show an increased amount of condensed chromatin and lower amounts of phosphorylated polymerase II and DNA/RNA hybrid molecules, clearly indicating a decrease in pre-mRNA transcription rate compared to adult animals. In addition, myonuclei of aged fibres show decreased amounts of nucleoplasmic splicing factors and an accumulation of cleavage factors, polyadenilated RNA and perichromatin granules, suggesting a reduction in the processing and transport rate of premRNA. During ageing, it seems therefore that in rat myonuclei the entire production chain of mRNA, from synthesis to cytoplasmic export, is less efficient. This failure likely contributes to the reduced responsiveness of muscle cells to anabolic stimuli in the elderly.

  5. Multiple soft limits of cosmological correlation functions

    International Nuclear Information System (INIS)

    Joyce, Austin; Khoury, Justin; Simonović, Marko

    2015-01-01

    We derive novel identities satisfied by inflationary correlation functions in the limit where two external momenta are taken to be small. We derive these statements in two ways: using background-wave arguments and as Ward identities following from the fixed-time path integral. Interestingly, these identities allow us to constrain some of the O(q 2 ) components of the soft limit, in contrast to their single-soft analogues. We provide several nontrivial checks of our identities both in the context of resonant non-Gaussianities and in small sound speed models. Additionally, we extend the relation at lowest order in external momenta to arbitrarily many soft legs, and comment on the many-soft extension at higher orders in the soft momentum. Finally, we consider how higher soft limits lead to identities satisfied by correlation functions in large-scale structure

  6. New generalized functions and multiplication of distributions

    International Nuclear Information System (INIS)

    Colombeau, J.F.

    1984-01-01

    Since its conception, Quantum Field Theory is based on 'heuristic' computations (in particular products of distributions) that, despite lots of effort, remained meaningless from a mathematical viewpoint. In this book the author presents a new mathematical theory giving a rigorous mathematical sense to these heuristic computations and, from a mathematical viewpoint, to all products of distributions. This new mathematical theory is a new theory of Generalized Functions defined on any open subset Ω of Rsup(n), which are much more general than the distributions on Ω. (Auth.)

  7. Geomicrobiology of Hydrothermal Vents in Yellowstone Lake: Phylogenetic and Functional Analysis suggest Importance of Geochemistry (Invited)

    Science.gov (United States)

    Inskeep, W. P.; Macur, R.; Jay, Z.; Clingenpeel, S.; Tenney, A.; Lavalvo, D.; Shanks, W. C.; McDermott, T.; Kan, J.; Gorby, Y.; Morgan, L. A.; Yooseph, S.; Varley, J.; Nealson, K.

    2010-12-01

    outflow channels of YNP. Analysis of functional genes present in the consensus metagenome sequence representing these populations indicate metabolic potential for oxidation of reduced sulfur and hydrogen, both of which are present at high concentrations in these vent ecosystems. Metagenome sequence of biomass associated with sediments from hydrothermal vents at Mary Bay (50 m depth) suggest greater archaeal and bacterial diversity in this environment, which may be due to higher concentrations of hydrogen, iron, and manganese measured in these environments. Results from metagenome sequence and modest 16S rRNA gene surveys from hydrothermal vent biomass indicate that several groups of novel thermophilic archaea inhabit these sites, and in many cases, are represented by organisms not found in YNP terrestrial geothermal environments that have been characterized to date. The hydrothermal vents from Inflated Plain and West Thumb indicate a linkage between various geochemical attributes (sulfide, hydrogen) and the metabolic potential associated with dominant Aquificales populations present in these communities.

  8. Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients

    NARCIS (Netherlands)

    Franken, Ingmar H. A.; Stam, Cornelis J.; Hendriks, Vincent M.; van den Brink, Wim

    2004-01-01

    Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic ( EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In

  9. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

    NARCIS (Netherlands)

    C.A. Ibrahim-Verbaas (Carla); J. Bressler; S. Debette (Stéphanie); M. Schuur (Maaike); A.V. Smith; J.C. Bis (Joshua); G. Davies (Gail); S. Trompet (Stella); J.A. Smith; A. Björnsson (Asgeir); L.B. Chibnik (Lori); Y. Liu; V. Vitart (Veronique); M. Kirin (Mirna); K. Petrovic (Katja); O. Polasek (Ozren); L. Zgaga (Lina); C. Fawns-Ritchie; P. Hoffmann (Per); J. Karjalainen (Juha); J. Lahti; D.J. Llewellyn; C.O. Schmidt (Carsten O.); R. Mather; V. Chouraki (Vincent); Q. Sun; S. Resnick (Susan); L.M. Rose (Lynda M.); C. Oldmeadow (Christopher); M. Stewart; B.H. Smith; V. Gudnason (Vilmundur); Q. Yang (Qiong); S.S. Mirza (Saira); J.W. Jukema; P.L. DeJager (Philip L.); T.B. Harris (Tamara); D.C. Liewald (David C.); N. Amin (Najaf); L.H. Coker (Laura); O. Stegle (Oliver); O.L. Lopez; R. Schmidt; A. Teumer (Alexander); I. Ford; N. Karbalai (Nazanin); J.T. Becker (James); M.K. Jonsdottir (Maria K.); R. Au; R.S.N. Fehrmann (Rudolf); S. Herms (Stefan); M.A. Nalls (Michael); W. Zhao; S.T. Turner; K. Yaffe; K. Lohman (Kurt); J.C. van Swieten (John); S.L.R. Kardia; D.S. Knopman (David); W.M. Meeks (William); G. Heiss (Gerardo); E.G. Holliday (Elizabeth); P.W. Schofield; T. Tanaka (Toshiko); D.J. Stott (David J.); J. Wang (Jing); P.M. Ridker (Paul); A.J. Gow; A. Pattie (Alison); J.M. Starr (John); L.J. Hocking; N.J. Armstrong (Nicola J.); S. McLachlan (Stela); L. Shulman (Lee); L.C. Pilling (Luke); G. Eiriksdottir (Gudny); R.J. Scott; N.A. Kochan (Nicole A.); A. Palotie; Y.-C. Hsieh; J.G. Eriksson (Johan G.); A.D. Penman (Alan); R.F. Gottesman (Rebecca); B.A. Oostra (Ben); L. Yu; A.L. DeStefano (Anita L.); A. Beiser; M. Garcia; J.I. Rotter; M.M. Nöthen; A. Hofman (Albert); P.E. Slagboom (Eline); R.G.J. Westendorp; B.M. Buckley (Brendan M.); P.A. Wolf; A.G. Uitterlinden (André); B.M. Psaty (Bruce); H.J. Grabe (Hans Jörgen); S. Bandinelli (Stefania); D.I. Chasman (Daniel); F. Grodstein (Francine); K. Räikkönen (Katri); J.-C. Lambert; D.J. Porteous (David J.); J.F. Price (Jackie F.); P.S. Sachdev (Perminder); L. Ferrucci (Luigi); J. Attia (John); I. Rudan (Igor); C. Hayward; A.F. Wright; J.F. Wilson (James F); S. Cichon (Sven); L. Franke (Lude); H. Schmidt; J. Ding (Jingzhong); A.J. de Craen (Anton); M. Fornage (Myriam); D.A. Bennett (David); I.J. Deary (Ian); M.A. Ikram (Arfan); L.J. Launer (Lenore); A.L. Fitzpatrick; S. Seshadri (Sudha); C.M. van Duijn (Cornelia); T.H. Mosley (Thomas H.)

    2016-01-01

    textabstractTo identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and

  10. Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

    Science.gov (United States)

    Woods, Carol M.; Grimm, Kevin J.

    2011-01-01

    In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

  11. Assessment of patients with multiple sclerosis according to tests of the Multiple Sclerosis Functional Composite

    Directory of Open Access Journals (Sweden)

    Anelise Ineu Figueiredo

    Full Text Available Abstract Introduction: The Multiple Sclerosis Functional Composite (MSFC is a scale that evaluates the functional and cognitive aspects of patients with multiple sclerosis (MS. Objective: To compare the performance of individuals with the relapsing-remitting form of MS (RRMS with a group of healthy subjects using the MSFC. Methods: Twenty subjects were investigated in this study, consisting of 10 patients with clinical diagnosis of RRMS and 10 controls with similar gender and age to the group with the disease. The three tests that comprise the MSFC were used for the evaluation of gait, upper limb motor function and cognition (memory and processing speed. Student's t-test was used to assess data with normal distribution and data with skewed distribution were evaluated using the Mann-Whitney test. Results: The results showed that the patients with RRMS took longer to perform the locomotion test (6.91 ± 2.35 compared to the control group (5.16 ± 1.28. The MS group (22.06 ± 5.44 also showed greater difficulty in performing a task with the dominant upper limb compared to the healthy subjects (17.79 ± 2.96. No statistically significant difference was found between the groups in the performance of cognitive tasks (p = .65. Conclusion: The use of the MSFC tests proved valuable for measuring possible motor and cognitive impairments in patients with RRMS. Thus, it is suggested that this scale is adopted in clinical practice, improving therapies for the treatment of MS patients and thereby providing them a better quality of life.

  12. Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs.

    Science.gov (United States)

    Regad, Leslie; Martin, Juliette; Camproux, Anne-Claude

    2011-06-20

    One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function. Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model - Structural Alphabet), which allows simplification of protein structures into uni-dimensional sequences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i) ubiquitous motifs, shared by several superfamilies and (ii) superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P) and SAH/SAM. Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.

  13. Dissecting protein loops with a statistical scalpel suggests a functional implication of some structural motifs

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2011-06-01

    Full Text Available Abstract Background One of the strategies for protein function annotation is to search particular structural motifs that are known to be shared by proteins with a given function. Results Here, we present a systematic extraction of structural motifs of seven residues from protein loops and we explore their correspondence with functional sites. Our approach is based on the structural alphabet HMM-SA (Hidden Markov Model - Structural Alphabet, which allows simplification of protein structures into uni-dimensional sequences, and advanced pattern statistics adapted to short sequences. Structural motifs of interest are selected by looking for structural motifs significantly over-represented in SCOP superfamilies in protein loops. We discovered two types of structural motifs significantly over-represented in SCOP superfamilies: (i ubiquitous motifs, shared by several superfamilies and (ii superfamily-specific motifs, over-represented in few superfamilies. A comparison of ubiquitous words with known small structural motifs shows that they contain well-described motifs as turn, niche or nest motifs. A comparison between superfamily-specific motifs and biological annotations of Swiss-Prot reveals that some of them actually correspond to functional sites involved in the binding sites of small ligands, such as ATP/GTP, NAD(P and SAH/SAM. Conclusions Our findings show that statistical over-representation in SCOP superfamilies is linked to functional features. The detection of over-represented motifs within structures simplified by HMM-SA is therefore a promising approach for prediction of functional sites and annotation of uncharacterized proteins.

  14. Brief Report: Suggestibility, Compliance and Psychological Traits in High-Functioning Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Maras, Katie L.; Bowler, Dermot M.

    2012-01-01

    Individuals with autism spectrum disorder (ASD) may be over-represented within the criminal justice system; it is therefore important to understand how they fare under police questioning. The present study examined interrogative suggestibility and compliance in individuals with ASD, and whether this is associated with certain psychological traits.…

  15. Evaluating Functional Decline in Patients with Multiple Sclerosis

    Science.gov (United States)

    Rosenblum, Sara; Weiss, Patrice L.

    2010-01-01

    Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

  16. Using piecewise sinusoidal basis functions to blanket multiple wire segments

    CSIR Research Space (South Africa)

    Lysko, AA

    2009-06-01

    Full Text Available This paper discusses application of the piecewise sinusoidal (PWS) basis function (BF) over a chain of several wire segments, for example as a multiple domain basis function. The usage of PWS BF is compared to results based on the piecewise linear...

  17. Sampling intraspecific variability in leaf functional traits: Practical suggestions to maximize collected information.

    Science.gov (United States)

    Petruzzellis, Francesco; Palandrani, Chiara; Savi, Tadeja; Alberti, Roberto; Nardini, Andrea; Bacaro, Giovanni

    2017-12-01

    The choice of the best sampling strategy to capture mean values of functional traits for a species/population, while maintaining information about traits' variability and minimizing the sampling size and effort, is an open issue in functional trait ecology. Intraspecific variability (ITV) of functional traits strongly influences sampling size and effort. However, while adequate information is available about intraspecific variability between individuals (ITV BI ) and among populations (ITV POP ), relatively few studies have analyzed intraspecific variability within individuals (ITV WI ). Here, we provide an analysis of ITV WI of two foliar traits, namely specific leaf area (SLA) and osmotic potential (π), in a population of Quercus ilex L. We assessed the baseline ITV WI level of variation between the two traits and provided the minimum and optimal sampling size in order to take into account ITV WI , comparing sampling optimization outputs with those previously proposed in the literature. Different factors accounted for different amount of variance of the two traits. SLA variance was mostly spread within individuals (43.4% of the total variance), while π variance was mainly spread between individuals (43.2%). Strategies that did not account for all the canopy strata produced mean values not representative of the sampled population. The minimum size to adequately capture the studied functional traits corresponded to 5 leaves taken randomly from 5 individuals, while the most accurate and feasible sampling size was 4 leaves taken randomly from 10 individuals. We demonstrate that the spatial structure of the canopy could significantly affect traits variability. Moreover, different strategies for different traits could be implemented during sampling surveys. We partially confirm sampling sizes previously proposed in the recent literature and encourage future analysis involving different traits.

  18. On Multiple Interpolation Functions of the -Genocchi Polynomials

    Directory of Open Access Journals (Sweden)

    Jin Jeong-Hee

    2010-01-01

    Full Text Available Abstract Recently, many mathematicians have studied various kinds of the -analogue of Genocchi numbers and polynomials. In the work (New approach to q-Euler, Genocchi numbers and their interpolation functions, "Advanced Studies in Contemporary Mathematics, vol. 18, no. 2, pp. 105–112, 2009.", Kim defined new generating functions of -Genocchi, -Euler polynomials, and their interpolation functions. In this paper, we give another definition of the multiple Hurwitz type -zeta function. This function interpolates -Genocchi polynomials at negative integers. Finally, we also give some identities related to these polynomials.

  19. Kinetic and structural evidences on human prolidase pathological mutants suggest strategies for enzyme functional rescue.

    Directory of Open Access Journals (Sweden)

    Roberta Besio

    Full Text Available Prolidase is the only human enzyme responsible for the digestion of iminodipeptides containing proline or hydroxyproline at their C-terminal end, being a key player in extracellular matrix remodeling. Prolidase deficiency (PD is an intractable loss of function disease, characterized by mutations in the prolidase gene. The exact causes of activity impairment in mutant prolidase are still unknown. We generated three recombinant prolidase forms, hRecProl-231delY, hRecProl-E412K and hRecProl-G448R, reproducing three mutations identified in homozygous PD patients. The enzymes showed very low catalytic efficiency, thermal instability and changes in protein conformation. No variation of Mn(II cofactor affinity was detected for hRecProl-E412K; a compromised ability to bind the cofactor was found in hRecProl-231delY and Mn(II was totally absent in hRecProl-G448R. Furthermore, local structure perturbations for all three mutants were predicted by in silico analysis. Our biochemical investigation of the three causative alleles identified in perturbed folding/instability, and in consequent partial prolidase degradation, the main reasons for enzyme inactivity. Based on the above considerations we were able to rescue part of the prolidase activity in patients' fibroblasts through the induction of Heath Shock Proteins expression, hinting at new promising avenues for PD treatment.

  20. Genetic evidence suggests that GIS functions downstream of TCL1 to regulate trichome formation in Arabidopsis.

    Science.gov (United States)

    Zhang, Na; Yang, Li; Luo, Sha; Wang, Xutong; Wang, Wei; Cheng, Yuxin; Tian, Hainan; Zheng, Kaijie; Cai, Ling; Wang, Shucai

    2018-04-13

    Trichome formation in Arabidopsis is regulated by a MBW complex formed by MYB, bHLH and WD40 transcriptional factors, which can activate GLABRA2 (GL2) and the R3 MYB transcription factor genes. GL2 promotes trichome formation, whereas R3 MYBs are able to block the formation of the MBW complex. It has been reported that the C2H2 transcription factor GIS (GLABROUS INFLORESCENCE STEMS) functions upstream of the MBW activator complex to regulate trichome formation, and that the expression of TCL1 is not regulated by the MBW complex. However, gis and the R3 MYB gene mutant tcl1 (trichomeless 1) have opposite inflorescence trichome phenotypes, but their relationship in regulating trichome formation remained unknown. By generating and characterization of the gis tcl1 double mutant, we found that trichome formation in the gis tcl1double and the tcl1 single mutants were largely indistinguishable, but the trichome formation in the 35S:TCL1/gis transgenic plant was similar to that in the gis mutant. By using quantitative RT-PCR analysis, we showed that expression level of GIS was increased in the triple mutant tcl1 try cpc, but the expression level of TCL1 was not affected in the gis mutant. On the other hand, trichome morphology in both gis tcl1 and 35S:TCL1/gis plants was similar to that in the gis mutant. In summary, our results indicate that GIS may work downstream of TCL1 to regulate trichome formation, and GIS has a dominant role in controlling trichome morphology.

  1. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

    Science.gov (United States)

    Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

    2017-01-01

    Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  2. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Mario Stampanoni Bassi

    2017-12-01

    Full Text Available Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS, structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  3. QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms

    Czech Academy of Sciences Publication Activity Database

    Mlýnský, V.; Banáš, P.; Walter, N.G.; Šponer, Jiří; Otyepka, M.

    2011-01-01

    Roč. 115, č. 47 (2011), s. 13911-13924 ISSN 1520-6106 R&D Projects: GA ČR(CZ) GAP208/10/2302; GA ČR(CZ) GA203/09/1476; GA ČR(CZ) GAP208/11/1822 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : TRANSITION-STATE STABILIZATION * BASE-PHOSPHATE INTERACTIONS * DENSITY-FUNCTIONAL THEORY Subject RIV: BO - Biophysics Impact factor: 3.696, year: 2011

  4. Functional analysis screening for multiple topographies of problem behavior.

    Science.gov (United States)

    Bell, Marlesha C; Fahmie, Tara A

    2018-04-23

    The current study evaluated a screening procedure for multiple topographies of problem behavior in the context of an ongoing functional analysis. Experimenters analyzed the function of a topography of primary concern while collecting data on topographies of secondary concern. We used visual analysis to predict the function of secondary topographies and a subsequent functional analysis to test those predictions. Results showed that a general function was accurately predicted for five of six (83%) secondary topographies. A specific function was predicted and supported for a subset of these topographies. The experimenters discuss the implication of these results for clinicians who have limited time for functional assessment. © 2018 Society for the Experimental Analysis of Behavior.

  5. Multiple function benefit - cost comparison of conservation buffer placement strategies

    Science.gov (United States)

    Z. Qiu; M.G. Dosskey

    2012-01-01

    Conservation buffers are considered to be effective practices for repairing impaired streams and restoring multiple ecosystem functions in degraded agricultural watersheds. Six different planning strategies for targeting their placement within watersheds were compared in terms of cost-effectiveness for environmental improvement in the 144 km² Neshanic River...

  6. Gender-related differences in functional connectivity in multiple sclerosis

    NARCIS (Netherlands)

    Schoonheim, M.M.; Hulst, H.E.; Landi, D.; Ciccarelli, O.; Roosendaal, S.D.; Sanz-Arigita, E.J.; Vrenken, H.; Polman, C.H.; Stam, C.J.; Barkhof, F.; Geurts, J.J.G.

    2012-01-01

    Background: Gender effects are strong in multiple sclerosis (MS), with male patients showing a worse clinical outcome than female patients. Functional reorganization of neural activity may contribute to limit disability, and possible gender differences in this process may have important clinical

  7. Strong population genetic structuring in an annual fish, Nothobranchius furzeri, suggests multiple savannah refugia in southern Mozambique.

    Science.gov (United States)

    Bartáková, Veronika; Reichard, Martin; Janko, Karel; Polačik, Matej; Blažek, Radim; Reichwald, Kathrin; Cellerino, Alessandro; Bryja, Josef

    2013-09-12

    Intraspecific genetic variation of African fauna has been significantly affected by pronounced climatic fluctuations in Plio-Pleistocene, but, with the exception of large mammals, very limited empirical data on diversity of natural populations are available for savanna-dwelling animals. Nothobranchius furzeri is an annual fish from south-eastern Africa, inhabiting discrete temporary savannah pools outside main river alluvia. Their dispersal is limited and population processes affecting its genetic structure are likely a combination of those affecting terrestrial and aquatic taxa. N. furzeri is a model taxon in ageing research and several populations of known geographical origin are used in laboratory studies. Here, we analysed the genetic structure, diversity, historical demography and temporal patterns of divergence in natural populations of N. furzeri across its entire distribution range. Genetic structure and historical demography of N. furzeri were analysed using a combination of mitochondrial (partial cytochrome b sequences, 687 bp) and nuclear (13 microsatellites) markers in 693 fish from 36 populations. Genetic markers consistently demonstrated strong population structuring and suggested two main genetic groups associated with river basins. The split was dated to the Pliocene (>2 Mya). The northern group inhabits savannah pools across the basin of the intermittent river Chefu in south-western Mozambique and eastern Zimbabwe. The southern group (from southernmost Mozambique) is subdivided, with the River Limpopo forming a barrier (maximum divergence time 1 Mya). A strong habitat fragmentation (isolated temporary pools) is reflected in significant genetic structuring even between adjacent pools, with a major influence of genetic drift and significant isolation-by-distance. Analysis of historical demography revealed that the expansion of both groups is ongoing, supported by frequent founder effects in marginal parts of the range and evidence of secondary

  8. Predicting Protein Function via Semantic Integration of Multiple Networks.

    Science.gov (United States)

    Yu, Guoxian; Fu, Guangyuan; Wang, Jun; Zhu, Hailong

    2016-01-01

    Determining the biological functions of proteins is one of the key challenges in the post-genomic era. The rapidly accumulated large volumes of proteomic and genomic data drives to develop computational models for automatically predicting protein function in large scale. Recent approaches focus on integrating multiple heterogeneous data sources and they often get better results than methods that use single data source alone. In this paper, we investigate how to integrate multiple biological data sources with the biological knowledge, i.e., Gene Ontology (GO), for protein function prediction. We propose a method, called SimNet, to Semantically integrate multiple functional association Networks derived from heterogenous data sources. SimNet firstly utilizes GO annotations of proteins to capture the semantic similarity between proteins and introduces a semantic kernel based on the similarity. Next, SimNet constructs a composite network, obtained as a weighted summation of individual networks, and aligns the network with the kernel to get the weights assigned to individual networks. Then, it applies a network-based classifier on the composite network to predict protein function. Experiment results on heterogenous proteomic data sources of Yeast, Human, Mouse, and Fly show that, SimNet not only achieves better (or comparable) results than other related competitive approaches, but also takes much less time. The Matlab codes of SimNet are available at https://sites.google.com/site/guoxian85/simnet.

  9. Molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in Arizona during 2001-2009.

    Directory of Open Access Journals (Sweden)

    Ivan V Kuzmin

    Full Text Available In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly during 2001-2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T₂₄₂ in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain. Roles of the amino acid changes, detected in our

  10. Multiple functions of the S-phase checkpoint mediator.

    Science.gov (United States)

    Tanaka, Katsunori

    2010-01-01

    There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.

  11. Towards Integration of Biological and Physiological Functions at Multiple Levels

    Directory of Open Access Journals (Sweden)

    Taishin eNomura

    2010-12-01

    Full Text Available An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.

  12. The ALMT Gene Family Performs Multiple Functions in Plants

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2018-02-01

    Full Text Available The aluminium activated malate transporter (ALMT gene family is named after the first member of the family identified in wheat (Triticum aestivum L.. The product of this gene controls resistance to aluminium (Al toxicity. ALMT genes encode transmembrane proteins that function as anion channels and perform multiple functions involving the transport of organic anions (e.g., carboxylates and inorganic anions in cells. They share a PF11744 domain and are classified in the Fusaric acid resistance protein-like superfamily, CL0307. The proteins typically have five to seven transmembrane regions in the N-terminal half and a long hydrophillic C-terminal tail but predictions of secondary structure vary. Although widely spread in plants, relatively little information is available on the roles performed by other members of this family. In this review, we summarized functions of ALMT gene families, including Al resistance, stomatal function, mineral nutrition, microbe interactions, fruit acidity, light response and seed development.

  13. Multiple victimization experiences of urban elementary school students: associations with psychosocial functioning and academic performance.

    Science.gov (United States)

    Holt, Melissa K; Finkelhor, David; Kantor, Glenda Kaufman

    2007-05-01

    This study explored the victimization experiences of urban elementary school students to determine whether subsets of youth emerged with similar victimization profiles (e.g., no victimization, multiple types of victimization). It also evaluated whether multiple victimization was associated with greater psychological distress and lower academic performance. Participants were 689 fifth grade students from an urban, ethnically diverse school district in the Northeast. Youth completed self-report measures in school about bullying victimization, victimization in the home and community, and psychosocial functioning. Cluster analysis suggested the existence of three distinct youth profiles: those with minimal victimization, those victimized primarily by their peers, and those with multiple types of victimizations. As hypothesized, youth with multiple victimizations experienced more psychological distress and earned lower grades than their peers. Findings highlight the heterogeneity of youth victimization experiences and their relations to functioning, and have implications for treatment planning among practitioners working with youth.

  14. Multitasking in multiple sclerosis: can it inform vocational functioning?

    Science.gov (United States)

    Morse, Chelsea L; Schultheis, Maria T; McKeever, Joshua D; Leist, Thomas

    2013-12-01

    To examine associations between multitasking ability defined by performance on a complex task integrating multiple cognitive domains and vocational functioning in multiple sclerosis (MS). Survey data collection. Laboratory with referrals from an outpatient clinic. Community-dwelling individuals with MS (N=30) referred between October 2011 and June 2012. Not applicable. The modified Six Elements Test (SET) to measure multitasking ability, Fatigue Severity Scale to measure fatigue, several neuropsychological measures of executive functioning, and vocational status. Among the sample, 60% of individuals have reduced their work hours because of MS symptoms (cutback employment group) and 40% had maintained their work hours. Among both groups, SET performance was significantly associated with performance on several measures of neuropsychological functioning. Individuals in the cutback employment group demonstrated significantly worse overall performance on the SET (P=.041). Logistic regression was used to evaluate associations between SET performance and vocational status, while accounting for neuropsychological performance and fatigue. The overall model was significant (χ(2)3=8.65, P=.032), with fatigue [Exp(B)=.83, P=.01] and multitasking ability [Exp(B)=.60, P=.043] retained as significant predictors. Multitasking ability may play an important role in performance at work for individuals with MS. Given that multitasking was associated with vocational functioning, future efforts should assess the usefulness of incorporating multitasking ability into rehabilitation planning. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  15. Functional Genomics and Phylogenetic Evidence Suggest Genus-Wide Cobalamin Production by the Globally Distributed Marine Nitrogen Fixer Trichodesmium.

    Science.gov (United States)

    Walworth, Nathan G; Lee, Michael D; Suffridge, Christopher; Qu, Pingping; Fu, Fei-Xue; Saito, Mak A; Webb, Eric A; Sañudo-Wilhelmy, Sergio A; Hutchins, David A

    2018-01-01

    Only select prokaryotes can biosynthesize vitamin B 12 (i.e., cobalamins), but these organic co-enzymes are required by all microbial life and can be vanishingly scarce across extensive ocean biomes. Although global ocean genome data suggest cyanobacteria to be a major euphotic source of cobalamins, recent studies have highlighted that >95% of cyanobacteria can only produce a cobalamin analog, pseudo-B 12 , due to the absence of the BluB protein that synthesizes the α ligand 5,6-dimethylbenzimidizole (DMB) required to biosynthesize cobalamins. Pseudo-B 12 is substantially less bioavailable to eukaryotic algae, as only certain taxa can intracellularly remodel it to one of the cobalamins. Here we present phylogenetic, metagenomic, transcriptomic, proteomic, and chemical analyses providing multiple lines of evidence that the nitrogen-fixing cyanobacterium Trichodesmium transcribes and translates the biosynthetic, cobalamin-requiring BluB enzyme. Phylogenetic evidence suggests that the Trichodesmium DMB biosynthesis gene, bluB , is of ancient origin, which could have aided in its ecological differentiation from other nitrogen-fixing cyanobacteria. Additionally, orthologue analyses reveal two genes encoding iron-dependent B 12 biosynthetic enzymes (cbiX and isiB), suggesting that iron availability may be linked not only to new nitrogen supplies from nitrogen fixation, but also to B 12 inputs by Trichodesmium . These analyses suggest that Trichodesmium contains the genus-wide genomic potential for a previously unrecognized role as a source of cobalamins, which may prove to considerably impact marine biogeochemical cycles.

  16. Psychological functioning in primary progressive versus secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Vleugels, L; Pfennings, L E; Pouwer, F

    1998-01-01

    Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary...... progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2) and mean age of onset of MS of 30.7 years...... (SD 11.1). Patients completed questionnaires measuring among others the following aspects of psychological functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL-90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards handicap (GHAS). Patients with a PP...

  17. Mode Shape Analysis of Multiple Cracked Functionally Graded Timoshenko Beams

    Directory of Open Access Journals (Sweden)

    Tran Van Lien

    Full Text Available Abstract The present paper addresses free vibration of multiple cracked Timoshenko beams made of Functionally Graded Material (FGM. Cracks are modeled by rotational spring of stiffness calculated from the crack depth and material properties vary according to the power law throughout the beam thickness. Governing equations for free vibration of the beam are formulated with taking into account actual position of the neutral plane. The obtained frequency equation and mode shapes are used for analysis of the beam mode shapes in dependence on the material and crack parameters. Numerical results validate usefulness of the proposed herein theory and show that mode shapes are good indication for detecting multiple cracks in Timoshenko FGM beams.

  18. Progressive multiple sclerosis, cognitive function, and quality of life.

    Science.gov (United States)

    Højsgaard Chow, Helene; Schreiber, Karen; Magyari, Melinda; Ammitzbøll, Cecilie; Börnsen, Lars; Romme Christensen, Jeppe; Ratzer, Rikke; Soelberg Sørensen, Per; Sellebjerg, Finn

    2018-02-01

    Patients with progressive multiple sclerosis (MS) often have cognitive impairment in addition to physical impairment. The burden of cognitive and physical impairment progresses over time, and may be major determinants of quality of life. The aim of this study was to assess to which degree quality of life correlates with physical and cognitive function in progressive MS. This is a retrospective study of 52 patients with primary progressive ( N  = 18) and secondary progressive MS ( N  = 34). Physical disability was assessed using the Expanded Disability Status Scale, Timed 25 Foot Walk (T25FW) test and 9-Hole Peg Test (9HPT). Cognitive function was assessed using Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test, and Trail Making Test B (TRAIL-B). In addition, quality of life was assessed by the Short Form 36 (SF-36) questionnaire. Only measures of cognitive function correlated with the overall SF-36 quality of life score and the Mental Component Summary score from the SF-36. The only physical measure that correlated with a measure of quality of life was T25FW test, which correlated with the Physical Component Summary from the SF-36. We found no other significant correlations between the measures of cognitive function and the overall physical measures but interestingly, we found a possible relationship between the 9HPT score for the nondominant hand and the SDMT and TRAIL-B. Our findings support inclusion of measures of cognitive function in the assessment of patients with progressive MS as these correlated closer with quality of life than measures of physical impairment.

  19. Building a functional multiple intelligences theory to advance educational neuroscience.

    Science.gov (United States)

    Cerruti, Carlo

    2013-01-01

    A key goal of educational neuroscience is to conduct constrained experimental research that is theory-driven and yet also clearly related to educators' complex set of questions and concerns. However, the fields of education, cognitive psychology, and neuroscience use different levels of description to characterize human ability. An important advance in research in educational neuroscience would be the identification of a cognitive and neurocognitive framework at a level of description relatively intuitive to educators. I argue that the theory of multiple intelligences (MI; Gardner, 1983), a conception of the mind that motivated a past generation of teachers, may provide such an opportunity. I criticize MI for doing little to clarify for teachers a core misunderstanding, specifically that MI was only an anatomical map of the mind but not a functional theory that detailed how the mind actually processes information. In an attempt to build a "functional MI" theory, I integrate into MI basic principles of cognitive and neural functioning, namely interregional neural facilitation and inhibition. In so doing I hope to forge a path toward constrained experimental research that bears upon teachers' concerns about teaching and learning.

  20. Probability of detection as a function of multiple influencing parameters

    Energy Technology Data Exchange (ETDEWEB)

    Pavlovic, Mato

    2014-10-15

    Non-destructive testing is subject to measurement uncertainties. In safety critical applications the reliability assessment of its capability to detect flaws is therefore necessary. In most applications, the flaw size is the single most important parameter that influences the probability of detection (POD) of the flaw. That is why the POD is typically calculated and expressed as a function of the flaw size. The capability of the inspection system to detect flaws is established by comparing the size of reliably detected flaw with the size of the flaw that is critical for the structural integrity. Applications where several factors have an important influence on the POD are investigated in this dissertation. To devise a reliable estimation of the NDT system capability it is necessary to express the POD as a function of all these factors. A multi-parameter POD model is developed. It enables POD to be calculated and expressed as a function of several influencing parameters. The model was tested on the data from the ultrasonic inspection of copper and cast iron components with artificial flaws. Also, a technique to spatially present POD data called the volume POD is developed. The fusion of the POD data coming from multiple inspections of the same component with different sensors is performed to reach the overall POD of the inspection system.

  1. Fast, multiple optimizations of quadratic dose objective functions in IMRT

    International Nuclear Information System (INIS)

    Breedveld, Sebastiaan; Storchi, Pascal R M; Keijzer, Marleen; Heijmen, Ben J M

    2006-01-01

    Inverse treatment planning for intensity-modulated radiotherapy may include time consuming, multiple minimizations of an objective function. In this paper, methods are presented to speed up the process of (repeated) minimization of the well-known quadratic dose objective function, extended with a smoothing term that ensures generation of clinically acceptable beam profiles. In between two subsequent optimizations, the voxel-dependent importance factors of the quadratic terms will generally be adjusted, based on an intermediate plan evaluation. The objective function has been written in matrix-vector format, facilitating the use of a recently published, fast quadratic minimization algorithm, instead of commonly applied gradient-based methods. This format also reduces the calculation time in between subsequent minimizations, related to adjustment of the voxel-dependent importance factors. Sparse matrices are used to limit the required amount of computer memory. For three patients, comparisons have been made with a gradient method. Mean speed improvements of up to a factor of 37 have been achieved

  2. Wavefield reconstruction inversion with a multiplicative cost function

    Science.gov (United States)

    da Silva, Nuno V.; Yao, Gang

    2018-01-01

    We present a method for the automatic estimation of the trade-off parameter in the context of wavefield reconstruction inversion (WRI). WRI formulates the inverse problem as an optimisation problem, minimising the data misfit while penalising with a wave equation constraining term. The trade-off between the two terms is balanced by a scaling factor that balances the contributions of the data-misfit term and the constraining term to the value of the objective function. If this parameter is too large then it implies penalizing for the wave equation imposing a hard constraint in the inversion. If it is too small, then this leads to a poorly constrained solution as it is essentially penalizing for the data misfit and not taking into account the physics that explains the data. This paper introduces a new approach for the formulation of WRI recasting its formulation into a multiplicative cost function. We demonstrate that the proposed method outperforms the additive cost function when the trade-off parameter is appropriately scaled in the latter, when adapting it throughout the iterations, and when the data is contaminated with Gaussian random noise. Thus this work contributes with a framework for a more automated application of WRI.

  3. Probability of detection as a function of multiple influencing parameters

    International Nuclear Information System (INIS)

    Pavlovic, Mato

    2014-01-01

    Non-destructive testing is subject to measurement uncertainties. In safety critical applications the reliability assessment of its capability to detect flaws is therefore necessary. In most applications, the flaw size is the single most important parameter that influences the probability of detection (POD) of the flaw. That is why the POD is typically calculated and expressed as a function of the flaw size. The capability of the inspection system to detect flaws is established by comparing the size of reliably detected flaw with the size of the flaw that is critical for the structural integrity. Applications where several factors have an important influence on the POD are investigated in this dissertation. To devise a reliable estimation of the NDT system capability it is necessary to express the POD as a function of all these factors. A multi-parameter POD model is developed. It enables POD to be calculated and expressed as a function of several influencing parameters. The model was tested on the data from the ultrasonic inspection of copper and cast iron components with artificial flaws. Also, a technique to spatially present POD data called the volume POD is developed. The fusion of the POD data coming from multiple inspections of the same component with different sensors is performed to reach the overall POD of the inspection system.

  4. Contrasting expression of membrane metalloproteinases, MT1-MMP and MT3-MMP, suggests distinct functions in skeletal development.

    Science.gov (United States)

    Yang, Maozhou; Zhang, Bingbing; Zhang, Liang; Gibson, Gary

    2008-07-01

    Membrane-type 1 matrix metalloproteinase (MT1-MMP) is the most ubiquitous and widely studied of the membrane-type metalloproteinases (MT-MMPs). It was thus surprising to find no published data on chicken MT1-MMP. We report here the characterization of the chicken gene. Its low sequence identity with the MT1-MMP genes of other species, high GC content, and divergent catalytic domain explains the absence of data and our difficulties in characterizing the gene. The absence of structural features in the chicken gene that have been suggested to be critical for the activation of MMP-2 by MT1-MMP; for the effect of MT1-MMP on cell migration and for the recycling of MT1-MMP suggest these features are either not essential or that MT1-MMP does not perform these functions in chickens. Comparison of the expression of chicken MT1-MMP with MT3-MMP and with MMP-2 and MMP-13 has confirmed the previously recognized co-expression of MT1-MMP with MMP-2 and MMP-13 in fibrous and vascular tissues, particularly those surrounding the developing long bones in other species. By contrast, MT3-MMP expression differs markedly from that of MT1-MMP and of both MMP-2 and MMP-13. MT3-MMP is expressed by chondrocytes of the developing articular surface. Similar expression patterns of this group of MT-MMPs and MMPs have been observed in mouse embryos and suggest distinct and specific functions for MT1-MMP and MT3-MMP in skeletal development.

  5. Awareness of single and multiple emotions in high-functioning childeren with autism

    OpenAIRE

    Rieffe, C.J.; Meerum Terwogt, M.; Kotronopoulo, K.

    2007-01-01

    This study examined emotional awareness in children with autism. Twenty-two high functioning children with autism (mean age 10 years and 2 months) and 22 typically developing children, matched for age and gender, were presented with the four basic emotions (happiness, anger, sadness and fear) in single and multiple emotion tasks. Findings suggest that children with autism have difficulties identifying their own emotions and less developed emotion concepts (which causes an impaired capacity to...

  6. Multiple image x-radiography for functional lung imaging

    Science.gov (United States)

    Aulakh, G. K.; Mann, A.; Belev, G.; Wiebe, S.; Kuebler, W. M.; Singh, B.; Chapman, D.

    2018-01-01

    Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.

  7. Abnormal immune system development and function in schizophrenia helps reconcile diverse findings and suggests new treatment and prevention strategies.

    Science.gov (United States)

    Anders, Sherry; Kinney, Dennis K

    2015-08-18

    Extensive research implicates disturbed immune function and development in the etiology and pathology of schizophrenia. In addition to reviewing evidence for immunological factors in schizophrenia, this paper discusses how an emerging model of atypical immune function and development helps explain a wide variety of well-established - but puzzling - findings about schizophrenia. A number of theorists have presented hypotheses that early immune system programming, disrupted by pre- and perinatal adversity, often combines with abnormal brain development to produce schizophrenia. The present paper focuses on the hypothesis that disruption of early immune system development produces a latent immune vulnerability that manifests more fully after puberty, when changes in immune function and the thymus leave individuals more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Complementing neurodevelopmental models, this hypothesis integrates findings on many contributing factors to schizophrenia, including prenatal adversity, genes, climate, migration, infections, and stress, among others. It helps explain, for example, why (a) schizophrenia onset is typically delayed until years after prenatal adversity, (b) individual risk factors alone often do not lead to schizophrenia, and (c) schizophrenia prevalence rates actually tend to be higher in economically advantaged countries. Here we discuss how the hypothesis explains 10 key findings, and suggests new, potentially highly cost-effective, strategies for treatment and prevention of schizophrenia. Moreover, while most human research linking immune factors to schizophrenia has been correlational, these strategies provide ethical ways to experimentally test in humans theories about immune function and schizophrenia. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. A Unified Approach to Functional Principal Component Analysis and Functional Multiple-Set Canonical Correlation.

    Science.gov (United States)

    Choi, Ji Yeh; Hwang, Heungsun; Yamamoto, Michio; Jung, Kwanghee; Woodward, Todd S

    2017-06-01

    Functional principal component analysis (FPCA) and functional multiple-set canonical correlation analysis (FMCCA) are data reduction techniques for functional data that are collected in the form of smooth curves or functions over a continuum such as time or space. In FPCA, low-dimensional components are extracted from a single functional dataset such that they explain the most variance of the dataset, whereas in FMCCA, low-dimensional components are obtained from each of multiple functional datasets in such a way that the associations among the components are maximized across the different sets. In this paper, we propose a unified approach to FPCA and FMCCA. The proposed approach subsumes both techniques as special cases. Furthermore, it permits a compromise between the techniques, such that components are obtained from each set of functional data to maximize their associations across different datasets, while accounting for the variance of the data well. We propose a single optimization criterion for the proposed approach, and develop an alternating regularized least squares algorithm to minimize the criterion in combination with basis function approximations to functions. We conduct a simulation study to investigate the performance of the proposed approach based on synthetic data. We also apply the approach for the analysis of multiple-subject functional magnetic resonance imaging data to obtain low-dimensional components of blood-oxygen level-dependent signal changes of the brain over time, which are highly correlated across the subjects as well as representative of the data. The extracted components are used to identify networks of neural activity that are commonly activated across the subjects while carrying out a working memory task.

  9. The structure of Plasmodium vivax phosphatidylethanolamine-binding protein suggests a functional motif containing a left-handed helix

    International Nuclear Information System (INIS)

    Arakaki, Tracy; Neely, Helen; Boni, Erica; Mueller, Natasha; Buckner, Frederick S.; Van Voorhis, Wesley C.; Lauricella, Angela; DeTitta, George; Luft, Joseph; Hol, Wim G. J.; Merritt, Ethan A.

    2007-01-01

    The crystal structure of a phosphatidylethanolamine-binding protein from P. vivax, a homolog of Raf-kinase inhibitor protein (RKIP), has been solved to a resolution of 1.3 Å. The inferred interaction surface near the anion-binding site is found to include a distinctive left-handed α-helix. The structure of a putative Raf kinase inhibitor protein (RKIP) homolog from the eukaryotic parasite Plasmodium vivax has been studied to a resolution of 1.3 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protozoan protein is topologically similar to previously studied members of the phosphatidylethanolamine-binding protein (PEBP) sequence family, but exhibits a distinctive left-handed α-helical region at one side of the canonical phospholipid-binding site. Re-examination of previously determined PEBP structures suggests that the P. vivax protein and yeast carboxypeptidase Y inhibitor may represent a structurally distinct subfamily of the diverse PEBP-sequence family

  10. Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin.

    Science.gov (United States)

    Li, Zhengxiao; Hu, Lizhi; Elias, Peter M; Man, Mao-Qiang

    2018-02-01

    Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin. To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin. Following topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter. Our results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration. Our results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Zebrafish models of BAG3 myofibrillar myopathy suggest a toxic gain of function leading to BAG3 insufficiency.

    Science.gov (United States)

    Ruparelia, Avnika A; Oorschot, Viola; Vaz, Raquel; Ramm, Georg; Bryson-Richardson, Robert J

    2014-12-01

    Mutations in the co-chaperone Bcl2-associated athanogene 3 (BAG3) can cause myofibrillar myopathy (MFM), a childhood-onset progressive muscle disease, characterized by the formation of protein aggregates and myofibrillar disintegration. In contrast to other MFM-causing proteins, BAG3 has no direct structural role, but regulates autophagy and the degradation of misfolded proteins. To investigate the mechanism of disease in BAG3-related MFM, we expressed wild-type BAG3 or the dominant MFM-causing BAG3 (BAG3(P209L)) in zebrafish. Expression of the mutant protein results in the formation of aggregates that contain wild-type BAG3. Through the stimulation and inhibition of autophagy, we tested the prevailing hypothesis that impaired autophagic function is responsible for the formation of protein aggregates. Contrary to the existing theory, our studies reveal that inhibition of autophagy is not sufficient to induce protein aggregation. Expression of the mutant protein, however, did not induce myofibrillar disintegration and we therefore examined the effect of knocking down Bag3 function. Loss of Bag3 resulted in myofibrillar disintegration, but not in the formation of protein aggregates. Remarkably, BAG3(P209L) is able to rescue the myofibrillar disintegration phenotype, further demonstrating that its function is not impaired. Together, our knockdown and overexpression experiments identify a mechanism whereby BAG3(P209L) aggregates form, gradually reducing the pool of available BAG3, which eventually results in BAG3 insufficiency and myofibrillar disintegration. This mechanism is consistent with the childhood onset and progressive nature of MFM and suggests that reducing aggregation through enhanced degradation or inhibition of nucleation would be an effective therapy for this disease.

  12. Decreasing Multicollinearity: A Method for Models with Multiplicative Functions.

    Science.gov (United States)

    Smith, Kent W.; Sasaki, M. S.

    1979-01-01

    A method is proposed for overcoming the problem of multicollinearity in multiple regression equations where multiplicative independent terms are entered. The method is not a ridge regression solution. (JKS)

  13. A northward colonisation of the Andes by the potato cyst nematode during geological times suggests multiple host-shifts from wild to cultivated potatoes.

    Science.gov (United States)

    Picard, Damien; Sempere, Thierry; Plantard, Olivier

    2007-02-01

    The cyst nematode Globodera pallida is a major pest of potato in South America where this specialist parasite is native. To investigate its phylogeography, we have genotyped individuals from 42 Peruvian populations using mitochondrial and nuclear molecular markers. A clear south-to-north phylogeographical pattern was revealed with five well-supported clades. The clade containing the southern populations is genetically more diverse and forms the most basal branch. The large divergence among cytochrome b haplotypes suggests that they diverged before human domestication of potato. As the nematodes studied have been sampled on cultivated potato, multiple host-shifts from wild to cultivated potatoes must have occurred independently in each clade. We hypothesise that this south-to-north pattern took place during the uplift of the Andes beginning 20 My ago and following the same direction. To our knowledge, this is the first study of a plant parasite sampled on cultivated plants revealing an ancient phylogeographical pattern.

  14. Diversifying selection and functional analysis of interleukin-4 suggests antagonism-driven evolution at receptor-binding interfaces

    Directory of Open Access Journals (Sweden)

    Brown Scott

    2010-07-01

    Full Text Available Abstract Background Interleukin-4 (IL4 is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths 1. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. Results This analysis revealed evidence of diversifying selection at 15 residues, clustered in epitopes responsible for IL4 binding to its Type I and Type II receptors. Such a striking signature of selective pressure suggested either recurrent episodes of pathogen antagonism or ligand/receptor co-evolution. To test the latter possibility, we performed detailed functional analysis of IL4 allotypes expressed by Mus musculus musculus and Mus musculus castaneus, which happen to differ at 5 residues (including three at positively selected sites in and adjacent to the site 1 epitope that binds the IL4Rα subunit shared by the Type I and Type II IL4 receptors. We show that this intra-species variation affects the ability of IL4 neither to bind IL4 receptor alpha (IL4Rα nor to signal biological responses through its Type I receptor. Conclusions Our results -- reminiscent of clustered positively selected sites revealing functionally important residues at host-virus interaction interfaces -- are consistent with IL4 having evolved to avoid recurrent pathogen antagonism, while maintaining the capacity to bind and signal through its cognate receptor. This work exposes what may be a general feature of evolutionary conflicts fought by pathogen antagonists at host protein-protein interaction interfaces involved in immune signaling: the emergence of receptor-binding ligand epitopes capable of buffering amino acid variation.

  15. Diverse mitotic functions of the cytoskeletal cross-linking protein Shortstop suggest a role in Dynein/Dynactin activity.

    Science.gov (United States)

    Dewey, Evan B; Johnston, Christopher A

    2017-09-15

    Proper assembly and orientation of the bipolar mitotic spindle is critical to the fidelity of cell division. Mitotic precision fundamentally contributes to cell fate specification, tissue development and homeostasis, and chromosome distribution within daughter cells. Defects in these events are thought to contribute to several human diseases. The underlying mechanisms that function in spindle morphogenesis and positioning remain incompletely defined, however. Here we describe diverse roles for the actin-microtubule cross-linker Shortstop (Shot) in mitotic spindle function in Drosophila Shot localizes to mitotic spindle poles, and its knockdown results in an unfocused spindle pole morphology and a disruption of proper spindle orientation. Loss of Shot also leads to chromosome congression defects, cell cycle progression delay, and defective chromosome segregation during anaphase. These mitotic errors trigger apoptosis in Drosophila epithelial tissue, and blocking this apoptotic response results in a marked induction of the epithelial-mesenchymal transition marker MMP-1. The actin-binding domain of Shot directly interacts with Actin-related protein-1 (Arp-1), a key component of the Dynein/Dynactin complex. Knockdown of Arp-1 phenocopies Shot loss universally, whereas chemical disruption of F-actin does so selectively. Our work highlights novel roles for Shot in mitosis and suggests a mechanism involving Dynein/Dynactin activation. © 2017 Dewey and Johnston. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  16. Functional and Expression Analyses of the Pneumocystis MAT Genes Suggest Obligate Sexuality through Primary Homothallism within Host Lungs

    Directory of Open Access Journals (Sweden)

    S. Richard

    2018-02-01

    Full Text Available Fungi of the genus Pneumocystis are obligate parasites that colonize mammals’ lungs and are host species specific. Pneumocystis jirovecii and Pneumocystis carinii infect, respectively, humans and rats. They can turn into opportunistic pathogens in immunosuppressed hosts, causing severe pneumonia. Their cell cycle is poorly known, mainly because of the absence of an established method of culture in vitro. It is thought to include both asexual and sexual phases. Comparative genomic analysis suggested that their mode of sexual reproduction is primary homothallism involving a single mating type (MAT locus encompassing plus and minus genes (matMc, matMi, and matPi; Almeida et al., mBio 6:e02250-14, 2015. Thus, each strain would be capable of sexual reproduction alone (self-fertility. However, this is a working hypothesis derived from computational analyses that is, in addition, based on the genome sequences of single isolates. Here, we tested this hypothesis in the wet laboratory. The function of the P. jirovecii and P. carinii matMc genes was ascertained by restoration of sporulation in the corresponding mutant of fission yeast. Using PCR, we found the same single MAT locus in all P. jirovecii isolates and showed that all three MAT genes are often concomitantly expressed during pneumonia. Extensive homology searches did not identify other types of MAT transcription factors in the genomes or cis-acting motifs flanking the MAT locus that could have been involved in MAT switching or silencing. Our observations suggest that Pneumocystis sexuality through primary homothallism is obligate within host lungs to complete the cell cycle, i.e., produce asci necessary for airborne transmission to new hosts.

  17. Medicare capitation model, functional status, and multiple comorbidities: model accuracy

    Science.gov (United States)

    Noyes, Katia; Liu, Hangsheng; Temkin-Greener, Helena

    2012-01-01

    Objective This study examined financial implications of CMS-Hierarchical Condition Categories (HCC) risk-adjustment model on Medicare payments for individuals with comorbid chronic conditions. Study Design The study used 1992-2000 data from the Medicare Current Beneficiary Survey and corresponding Medicare claims. The pairs of comorbidities were formed based on the prior evidence about possible synergy between these conditions and activities of daily living (ADL) deficiencies and included heart disease and cancer, lung disease and cancer, stroke and hypertension, stroke and arthritis, congestive heart failure (CHF) and osteoporosis, diabetes and coronary artery disease, CHF and dementia. Methods For each beneficiary, we calculated the actual Medicare cost ratio as the ratio of the individual’s annualized costs to the mean annual Medicare cost of all people in the study. The actual Medicare cost ratios, by ADLs, were compared to the HCC ratios under the CMS-HCC payment model. Using multivariate regression models, we tested whether having the identified pairs of comorbidities affects the accuracy of CMS-HCC model predictions. Results The CMS-HCC model underpredicted Medicare capitation payments for patients with hypertension, lung disease, congestive heart failure and dementia. The difference between the actual costs and predicted payments was partially explained by beneficiary functional status and less than optimal adjustment for these chronic conditions. Conclusions Information about beneficiary functional status should be incorporated in reimbursement models since underpaying providers for caring for population with multiple comorbidities may provide severe disincentives for managed care plans to enroll such individuals and to appropriately manage their complex and costly conditions. PMID:18837646

  18. Modeling of Glycerol-3-Phosphate Transporter Suggests a Potential ‘Tilt’ Mechanism involved in its Function

    Science.gov (United States)

    Tsigelny, Igor F.; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K.

    2009-01-01

    the “rocker switch” may apply to certain MFS transporters, intermediate “tilted” states may exist under certain circumstances or as transitional structures. While wet lab experimental confirmation is required, our results suggest that transport mechanisms in this transporter family should probably not be assumed to be conserved simply based on standard structural homology considerations. Furthermore, steered molecular dynamics elucidating energetic interactions of ligands with amino acid residues in an appropriately modeled transporter may have predictive value in understanding the impact of mutations and/or polymorphisms on transporter function. PMID:18942157

  19. Three-dimensional structure of the Trypanosome flagellum suggests that the paraflagellar rod functions as a biomechanical spring.

    Directory of Open Access Journals (Sweden)

    Louise C Hughes

    Full Text Available Flagellum motility is critical for normal human development and for transmission of pathogenic protozoa that cause tremendous human suffering worldwide. Biophysical principles underlying motility of eukaryotic flagella are conserved from protists to vertebrates. However, individual cells exhibit diverse waveforms that depend on cell-specific elaborations on basic flagellum architecture. Trypanosoma brucei is a uniflagellated protozoan parasite that causes African sleeping sickness. The T. brucei flagellum is comprised of a 9+2 axoneme and an extra-axonemal paraflagellar rod (PFR, but the three-dimensional (3D arrangement of the underlying structural units is poorly defined. Here, we use dual-axis electron tomography to determine the 3D architecture of the T. brucei flagellum. We define the T. brucei axonemal repeating unit. We observe direct connections between the PFR and axonemal dyneins, suggesting a mechanism by which mechanochemical signals may be transmitted from the PFR to axonemal dyneins. We find that the PFR itself is comprised of overlapping laths organized into distinct zones that are connected through twisting elements at the zonal interfaces. The overall structure has an underlying 57 nm repeating unit. Biomechanical properties inferred from PFR structure lead us to propose that the PFR functions as a biomechanical spring that may store and transmit energy derived from axonemal beating. These findings provide insight into the structural foundations that underlie the distinctive flagellar waveform that is a hallmark of T. brucei cell motility.

  20. Expression Patterns and Identified Protein-Protein Interactions Suggest That Cassava CBL-CIPK Signal Networks Function in Responses to Abiotic Stresses.

    Science.gov (United States)

    Mo, Chunyan; Wan, Shumin; Xia, Youquan; Ren, Ning; Zhou, Yang; Jiang, Xingyu

    2018-01-01

    Cassava is an energy crop that is tolerant of multiple abiotic stresses. It has been reported that the interaction between Calcineurin B-like (CBL) protein and CBL-interacting protein kinase (CIPK) is implicated in plant development and responses to various stresses. However, little is known about their functions in cassava. Herein, 8 CBL ( MeCBL ) and 26 CIPK ( MeCIPK ) genes were isolated from cassava by genome searching and cloning of cDNA sequences of Arabidopsis CBL s and CIPK s. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that the expression levels of MeCBL and MeCIPK genes were different in different tissues throughout the life cycle. The expression patterns of 7 CBL and 26 CIPK genes in response to NaCl, PEG, heat and cold stresses were analyzed by quantitative real-time PCR (qRT-PCR), and it was found that the expression of each was induced by multiple stimuli. Furthermore, we found that many pairs of CBLs and CIPKs could interact with each other via investigating the interactions between 8 CBL and 25 CIPK proteins using a yeast two-hybrid system. Yeast cells co-transformed with cassava MeCIPK24, MeCBL10 , and Na + /H + antiporter MeSOS1 genes exhibited higher salt tolerance compared to those with one or two genes. These results suggest that the cassava CBL-CIPK signal network might play key roles in response to abiotic stresses.

  1. Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels

    Directory of Open Access Journals (Sweden)

    Chika Sumiyoshi

    2015-09-01

    Full Text Available Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1 to identify which outcome factors predict occupational functioning, quantified as work hours, and 2 to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB, the UCSD Performance-based Skills Assessment-Brief (UPSA-B, and the Social Functioning Scale Individuals’ version modified for the MATRICS-PASS (Modified SFS for PASS, respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly and a multiple logistic regression analyses (predicting dichotomized work status based on work hours. ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60–70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

  2. Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels.

    Science.gov (United States)

    Sumiyoshi, Chika; Harvey, Philip D; Takaki, Manabu; Okahisa, Yuko; Sato, Taku; Sora, Ichiro; Nuechterlein, Keith H; Subotnik, Kenneth L; Sumiyoshi, Tomiki

    2015-09-01

    Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1) to identify which outcome factors predict occupational functioning, quantified as work hours, and 2) to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB), the UCSD Performance-based Skills Assessment-Brief (UPSA-B), and the Social Functioning Scale Individuals' version modified for the MATRICS-PASS (Modified SFS for PASS), respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly) and a multiple logistic regression analyses (predicting dichotomized work status based on work hours). ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60-70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

  3. Extreme MHC class I diversity in the sedge warbler (Acrocephalus schoenobaenus); selection patterns and allelic divergence suggest that different genes have different functions.

    Science.gov (United States)

    Biedrzycka, Aleksandra; O'Connor, Emily; Sebastian, Alvaro; Migalska, Magdalena; Radwan, Jacek; Zając, Tadeusz; Bielański, Wojciech; Solarz, Wojciech; Ćmiel, Adam; Westerdahl, Helena

    2017-07-05

    Recent work suggests that gene duplications may play an important role in the evolution of immunity genes. Passerine birds, and in particular Sylvioidea warblers, have highly duplicated major histocompatibility complex (MHC) genes, which are key in immunity, compared to other vertebrates. However, reasons for this high MHC gene copy number are yet unclear. High-throughput sequencing (HTS) allows MHC genotyping even in individuals with extremely duplicated genes. This HTS data can reveal evidence of selection, which may help to unravel the putative functions of different gene copies, i.e. neofunctionalization. We performed exhaustive genotyping of MHC class I in a Sylvioidea warbler, the sedge warbler, Acrocephalus schoenobaenus, using the Illumina MiSeq technique on individuals from a wild study population. The MHC diversity in 863 genotyped individuals by far exceeds that of any other bird species described to date. A single individual could carry up to 65 different alleles, a large proportion of which are expressed (transcribed). The MHC alleles were of three different lengths differing in evidence of selection, diversity and divergence within our study population. Alleles without any deletions and alleles containing a 6 bp deletion showed characteristics of classical MHC genes, with evidence of multiple sites subject to positive selection and high sequence divergence. In contrast, alleles containing a 3 bp deletion had no sites subject to positive selection and had low divergence. Our results suggest that sedge warbler MHC alleles that either have no deletion, or contain a 6 bp deletion, encode classical antigen presenting MHC molecules. In contrast, MHC alleles containing a 3 bp deletion may encode molecules with a different function. This study demonstrates that highly duplicated MHC genes can be characterised with HTS and that selection patterns can be useful for revealing neofunctionalization. Importantly, our results highlight the need to consider the

  4. Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion.

    Science.gov (United States)

    Albacker, Lee A; Wu, Jeremy; Smith, Peter; Warmuth, Markus; Stephens, Philip J; Zhu, Ping; Yu, Lihua; Chmielecki, Juliann

    2017-01-01

    Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

  5. Multiple-region directed functional connectivity based on phase delays.

    Science.gov (United States)

    Goelman, Gadi; Dan, Rotem

    2017-03-01

    Network analysis is increasingly advancing the field of neuroimaging. Neural networks are generally constructed from pairwise interactions with an assumption of linear relations between them. Here, a high-order statistical framework to calculate directed functional connectivity among multiple regions, using wavelet analysis and spectral coherence has been presented. The mathematical expression for 4 regions was derived and used to characterize a quartet of regions as a linear, combined (nonlinear), or disconnected network. Phase delays between regions were used to obtain network's temporal hierarchy and directionality. The validity of the mathematical derivation along with the effects of coupling strength and noise on its outcomes were studied by computer simulations of the Kuramoto model. The simulations demonstrated correct directionality for a large range of coupling strength and low sensitivity to Gaussian noise compared with pairwise coherences. The analysis was applied to resting-state fMRI data of 40 healthy young subjects to characterize the ventral visual system, motor system and default mode network (DMN). It was shown that the ventral visual system was predominantly composed of linear networks while the motor system and the DMN were composed of combined (nonlinear) networks. The ventral visual system exhibits its known temporal hierarchy, the motor system exhibits center ↔ out hierarchy and the DMN has dorsal ↔ ventral and anterior ↔ posterior organizations. The analysis can be applied in different disciplines such as seismology, or economy and in a variety of brain data including stimulus-driven fMRI, electrophysiology, EEG, and MEG, thus open new horizons in brain research. Hum Brain Mapp 38:1374-1386, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Microfluidic production of multiple emulsions and functional microcapsules

    NARCIS (Netherlands)

    Lee, Tae Yong; Choi, Tae Min; Shim, Tae Soup; Frijns, Raoul A.M.; Kim, Shin Hyun

    2016-01-01

    Recent advances in microfluidics have enabled the controlled production of multiple-emulsion drops with onion-like topology. The multiple-emulsion drops possess an intrinsic core-shell geometry, which makes them useful as templates to create microcapsules with a solid membrane. High flexibility

  7. Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

    Science.gov (United States)

    Balasubramaniam, Shanti; Lewis, B; Mock, D M; Said, H M; Tarailo-Graovac, M; Mattman, A; van Karnebeek, C D; Thorburn, D R; Rodenburg, R J; Christodoulou, J

    2017-01-01

    Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with

  8. Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

    Directory of Open Access Journals (Sweden)

    Leon French

    2017-05-01

    Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

  9. Selection of multiple umbrella species for functional and taxonomic diversity to represent urban biodiversity.

    Science.gov (United States)

    Sattler, T; Pezzatti, G B; Nobis, M P; Obrist, M K; Roth, T; Moretti, M

    2014-04-01

    Surrogates, such as umbrella species, are commonly used to reduce the complexity of quantifying biodiversity for conservation purposes. The presence of umbrella species is often indicative of high taxonomic diversity; however, functional diversity is now recognized as an important metric for biodiversity and thus should be considered when choosing umbrella species. We identified umbrella species associated with high taxonomic and functional biodiversity in urban areas in Switzerland. We analyzed 39,752 individuals of 574 animal species from 96 study plots and 1397 presences of 262 plant species from 58 plots. Thirty-one biodiversity measures of 7 taxonomic groups (plants, spiders, bees, ground beetles, lady bugs, weevils and birds) were included in within- and across-taxa analyses. Sixteen measures were taxonomical (species richness and species diversity), whereas 15 were functional (species traits including mobility, resource use, and reproduction). We used indicator value analysis to identify umbrella species associated with single or multiple biodiversity measures. Many umbrella species were indicators of high biodiversity within their own taxonomic group (from 33.3% in weevils to 93.8% in birds), to a lesser extent they were indicators across taxa. Principal component analysis revealed that umbrella species for multiple measures of biodiversity represented different aspects of biodiversity, especially with respect to measures of taxonomic and functional diversity. Thus, even umbrella species for multiple measures of biodiversity were complementary in the biodiversity aspects they represented. Thus, the choice of umbrella species based solely on taxonomic diversity is questionable and may not represent biodiversity comprehensively. Our results suggest that, depending on conservation priorities, managers should choose multiple and complementary umbrella species to assess the state of biodiversity. © 2013 Society for Conservation Biology.

  10. Individual Differences in Young Children's Suggestibility: Relations to Event Memory, Language Abilities, Working Memory, and Executive Functioning

    Science.gov (United States)

    Roebers, C.M.; Schneider, W.

    2005-01-01

    In this paper, two empirical studies are presented in which an attempt was made to explain individual differences in two different aspects of 4-year-olds' suggestibility, that is, their ability to resist false suggestions and memory impairments due to prior misinformation. As sources of individual differences cognitive skills along the information…

  11. An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis

    Directory of Open Access Journals (Sweden)

    Mohammed Ahmed M

    2009-07-01

    Full Text Available Abstract Background Four- or five-option multiple choice questions (MCQs are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Methods Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses. Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. Results The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88 functioning distractors. Only 52.2% (n = 805 of all distractors were functioning effectively and 10.2% (n = 158 had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. Conclusion The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

  12. An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis.

    Science.gov (United States)

    Tarrant, Marie; Ware, James; Mohammed, Ahmed M

    2009-07-07

    Four- or five-option multiple choice questions (MCQs) are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses). Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88) functioning distractors. Only 52.2% (n = 805) of all distractors were functioning effectively and 10.2% (n = 158) had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

  13. High-Resolution Printing of 3D Structures Using an Electrohydrodynamic Inkjet with Multiple Functional Inks.

    Science.gov (United States)

    An, Byeong Wan; Kim, Kukjoo; Lee, Heejoo; Kim, So-Yun; Shim, Yulhui; Lee, Dae-Young; Song, Jun Yeob; Park, Jang-Ung

    2015-08-05

    Electrohydrodynamic-inkjet-printed high-resolution complex 3D structures with multiple functional inks are demonstrated. Printed 3D structures can have a variety of fine patterns, such as vertical or helix-shaped pillars and straight or rounded walls, with high aspect ratios (greater than ≈50) and narrow diameters (≈0.7 μm). Furthermore, the formation of freestanding, bridge-like Ag wire structures on plastic substrates suggests substantial potentials as high-precision, flexible 3D interconnects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Functional Neuroanatomy Involved in Automatic order Mental Arithmetic and Recitation of the Multiplication Table

    Science.gov (United States)

    Wang, Li-Qun; Saito, Masao

    We used 1.5T functional magnetic resonance imaging (fMRI) to explore that which brain areas contribute uniquely to numeric computation. The BOLD effect activation pattern of metal arithmetic task (successive subtraction: actual calculation task) was compared with multiplication tables repetition task (rote verbal arithmetic memory task) response. The activation found in right parietal lobule during metal arithmetic task suggested that quantitative cognition or numeric computation may need the assistance of sensuous convert, such as spatial imagination and spatial sensuous convert. In addition, this mechanism may be an ’analog algorithm’ in the simple mental arithmetic processing.

  15. Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation

    Directory of Open Access Journals (Sweden)

    Srinivasan M

    2014-12-01

    Full Text Available Mythily Srinivasan,1 Corinne Blackburn,1 Debomoy K Lahiri2,3 1Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, 2Institute of Psychiatry Research, Department of Psychiatry, 3Department of Medical and Molecular Genetics, School of Medicine, Indiana University-Purdue University, Indianapolis, IN, USA Abstract: Glucocorticoid-induced leucine zipper (GILZ is a glucocorticoid responsive protein that links the nuclear factor-kappa B (NFκB and the glucocorticoid signaling pathways. Functional and binding studies suggest that the proline-rich region at the carboxy terminus of GILZ binds the p65 subunit of NFκB and suppresses the immunoinflammatory response. A widely-used strategy in the discovery of peptide drugs involves exploitation of the complementary surfaces of naturally occurring binding partners. Previously, we observed that a synthetic peptide (GILZ-P derived from the proline-rich region of GILZ bound activated p65 and ameliorated experimental encephalomyelitis. Here we characterize the secondary structure of GILZ-P by circular dichroic analysis. GILZ-P adopts an extended polyproline type II helical conformation consistent with the structural conformation commonly observed in interfaces of transient intermolecular interactions. To determine the potential application of GILZ-P in humans, we evaluated the toxicity and efficacy of the peptide drug in mature human macrophage-like THP-1 cells. Treatment with GILZ-P at a wide range of concentrations commonly used for peptide drugs was nontoxic as determined by cell viability and apoptosis assays. Functionally, GILZ-P suppressed proliferation and glutamate secretion by activated macrophages by inhibiting nuclear translocation of p65. Collectively, our data suggest that the GILZ-P has therapeutic potential in chronic CNS diseases where persistent inflammation leads to neurodegeneration such as multiple sclerosis and Alzheimer’s disease. Keywords

  16. Disentangling the complex evolutionary history of the Western Palearctic blue tits (Cyanistes spp.) - phylogenomic analyses suggest radiation by multiple colonization events and subsequent isolation.

    Science.gov (United States)

    Stervander, Martin; Illera, Juan Carlos; Kvist, Laura; Barbosa, Pedro; Keehnen, Naomi P; Pruisscher, Peter; Bensch, Staffan; Hansson, Bengt

    2015-05-01

    Isolated islands and their often unique biota continue to play key roles for understanding the importance of drift, genetic variation and adaptation in the process of population differentiation and speciation. One island system that has inspired and intrigued evolutionary biologists is the blue tit complex (Cyanistes spp.) in Europe and Africa, in particular the complex evolutionary history of the multiple genetically distinct taxa of the Canary Islands. Understanding Afrocanarian colonization events is of particular importance because of recent unconventional suggestions that these island populations acted as source of the widespread population in mainland Africa. We investigated the relationship between mainland and island blue tits using a combination of Sanger sequencing at a population level (20 loci; 12 500 nucleotides) and next-generation sequencing of single population representatives (>3 200 000 nucleotides), analysed in coalescence and phylogenetic frameworks. We found (i) that Afrocanarian blue tits are monophyletic and represent four major clades, (ii) that the blue tit complex has a continental origin and that the Canary Islands were colonized three times, (iii) that all island populations have low genetic variation, indicating low long-term effective population sizes and (iv) that populations on La Palma and in Libya represent relicts of an ancestral North African population. Further, demographic reconstructions revealed (v) that the Canary Islands, conforming to traditional views, hold sink populations, which have not served as source for back colonization of the African mainland. Our study demonstrates the importance of complete taxon sampling and an extensive multimarker study design to obtain robust phylogeographical inferences. © 2015 John Wiley & Sons Ltd.

  17. Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Wattjes, Mike P. [University of Bonn, Department of Radiology/Neuroradiology, Bonn (Germany); VU University Medical Center, MS Center Amsterdam, Department of Radiology, Amsterdam (Netherlands); Harzheim, Michael; Schmidt, Stephan [University of Bonn, Department of Neurology, Bonn (Germany); Lutterbey, Goetz G.; Schild, Hans H.; Traeber, Frank [University of Bonn, Department of Radiology/Neuroradiology, Bonn (Germany); Bogdanow, Manuela [University of Bonn, Department of Medical Biometrics, Informatics and Epidemiology, Bonn (Germany)

    2008-02-15

    The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS. (orig.)

  18. [Cost-effectiveness analysis of interferon beta-1b as treatment for patients with clinically isolated syndrome suggestive of multiple sclerosis in Spain].

    Science.gov (United States)

    Piñol, C

    2016-05-01

    The BENEFIT study has demonstrated the benefits of early treatment with interferon beta 1b (IFNβ-1b). The objective of this study was to estimate the efficiency of early vs delayed IFNβ-1b treatment in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in Spain. A Markov model reflecting the social perspective was developed with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients with CIS, whose health status had been measured on the Expanded Disability Symptom Scale (EDSS), included patients who received early IFNβ-1b treatment and those who did not. Data from the BENEFIT study were used to model EDSS progression and transitions to MS. Costs were estimated from published literature. Patient utilities were derived from EQ-5D data and published data. Mortality was estimated using life tables and EDSS data. Costs (€ at 2013 rates) and outcomes were discounted at 3% per annum. A probabilistic sensitivity analysis was performed. In the base case, both the incremental cost utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of IFNβ-1b versus no treatment were dominant (more effective and less costly) from a social perspective. From the perspective of the Spanish Health System, the ICUR was € 40,702/QALY and the ICER was € 13/relapse avoided. Early treatment with IFNβ-1b after a CIS versus delayed treatment is efficient from a social perspective, but it may not be efficient from the perspective of the NHS which does not take non health-related costs into account. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis

    International Nuclear Information System (INIS)

    Wattjes, Mike P.; Harzheim, Michael; Schmidt, Stephan; Lutterbey, Goetz G.; Schild, Hans H.; Traeber, Frank; Bogdanow, Manuela

    2008-01-01

    The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS. (orig.)

  20. A comparative study of single and multiple hand tasks using functional MRI

    International Nuclear Information System (INIS)

    Shin, Byung Suck; Lee, Ho Kyu; Park, Sung Tae; Kim, Dong Eun; Lee, Myung Jun; Choi, Choong Gon; Kim, Jae Kyun; Suh, Dae Chul; Lim, Tae Hwan

    1998-01-01

    The purpose of this study is to assess, using functional MRI and by comparing activated motor sensory areas, the independence of brain activation during single and alternative multiple hand tasks. The subjects were six healthy volunteers. Using at 1.5T Siemens system and single shot FID-EPI sequencing (T2 weighted image; TR/TE 0.96 msec/ 61msec, flip angle 90 deg, matrix size 96 x 128, slice thickness/gap 5 mm/0.8 mm, FOV 200 mm) and T1-weighted anatomic images, functional MRI was performed. The paradigm of motor tasks consisted of appositional finger movements; the first involved the separate use of the right, left, and both hands in sequence. Using cross-correlation method (threshold : 0.6) and fMRI analysis software (stimulate 5.0), functional images were obtained. The activated area of brain cortex, the number of pixel, the average percentage change in signal intensity, and correlation of the time-signal intensity curve in the activated motor area were analysed and compared between the two task groups. Statistical analysis involved the use of Wilcoxon signed-rank test. Brain activation did not differ according to whether the motor task was single or alternative. We therefore suggest that during multiple stimuli, the relevant functional area and neuronal column are activated independently. (author). 19 refs., 2 tabs., 3 figs

  1. Expression Patterns and Identified Protein-Protein Interactions Suggest That Cassava CBL-CIPK Signal Networks Function in Responses to Abiotic Stresses

    Directory of Open Access Journals (Sweden)

    Chunyan Mo

    2018-03-01

    Full Text Available Cassava is an energy crop that is tolerant of multiple abiotic stresses. It has been reported that the interaction between Calcineurin B-like (CBL protein and CBL-interacting protein kinase (CIPK is implicated in plant development and responses to various stresses. However, little is known about their functions in cassava. Herein, 8 CBL (MeCBL and 26 CIPK (MeCIPK genes were isolated from cassava by genome searching and cloning of cDNA sequences of Arabidopsis CBLs and CIPKs. Reverse-transcriptase polymerase chain reaction (RT-PCR analysis showed that the expression levels of MeCBL and MeCIPK genes were different in different tissues throughout the life cycle. The expression patterns of 7 CBL and 26 CIPK genes in response to NaCl, PEG, heat and cold stresses were analyzed by quantitative real-time PCR (qRT-PCR, and it was found that the expression of each was induced by multiple stimuli. Furthermore, we found that many pairs of CBLs and CIPKs could interact with each other via investigating the interactions between 8 CBL and 25 CIPK proteins using a yeast two-hybrid system. Yeast cells co-transformed with cassava MeCIPK24, MeCBL10, and Na+/H+ antiporter MeSOS1 genes exhibited higher salt tolerance compared to those with one or two genes. These results suggest that the cassava CBL-CIPK signal network might play key roles in response to abiotic stresses.

  2. Neutron generators with size scalability, ease of fabrication and multiple ion source functionalities

    Science.gov (United States)

    Elizondo-Decanini, Juan M

    2014-11-18

    A neutron generator is provided with a flat, rectilinear geometry and surface mounted metallizations. This construction provides scalability and ease of fabrication, and permits multiple ion source functionalities.

  3. Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors.

    Science.gov (United States)

    Villmann, Carmen; Hoffmann, Jutta; Werner, Markus; Kott, Sabine; Strutz-Seebohm, Nathalie; Nilsson, Tanja; Hollmann, Michael

    2008-10-01

    Although considerable progress has been made in characterizing the physiological function of the high-affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1- or KA2-containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non-functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and KA receptors.

  4. A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.

    Science.gov (United States)

    Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

    2015-07-07

    Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K(+) channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

  5. Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin

    OpenAIRE

    Li, Z; Hu, L; Elias, PM; Man, M-Q

    2018-01-01

    Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin.To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin.Following topical ...

  6. Suggested use of sensitive measures of memory to detect functional effects of maternal iodine supplementation on hippocampal development.

    Science.gov (United States)

    Bauer, Patricia J; Dugan, Jessica A

    2016-09-01

    Maternal hypothyroxinemia secondary to iodine deficiency may have neurodevelopmental effects on the specific neurocognitive domain of memory. Associated disruption of thyroid hormone-dependent protein synthesis in the hippocampus has the potential to result in compromised development of the structure with consequential impairments in memory function. Despite links between maternal iodine deficiency during gestation and lactation and abnormal hippocampal development in rat fetuses and pups, there has been little research on the specific function of memory in human infants and young children born to iodine-deficient mothers. Several candidate measures have proven to be sensitive to the effects of gestational iron deficiency on memory function in infants and young children, including habituation and dishabituation, imitation-based tasks, and event-related potentials. Such measures could be used to test the effects of maternal iodine supplementation on the specific neurocognitive domain of memory in infants and young children. Furthermore, progress in understanding the effects of maternal iodine supplementation on neurocognitive development could be accelerated by the development of a nonhuman primate model to complement the rodent model. © 2016 American Society for Nutrition.

  7. Considerable MHC diversity suggests that the functional extinction of baiji is not related to population genetic collapse.

    Directory of Open Access Journals (Sweden)

    Shixia Xu

    Full Text Available To further extend our understanding of the mechanism causing the current nearly extinct status of the baiji (Lipotes vexillifer, one of the most critically endangered species in the world, genetic diversity at the major histocompatibility complex (MHC class II DRB locus was investigated in the baiji. Nine highly divergent DRB alleles were identified in 17 samples, with an average of 28.4 (13.2% nucleotide difference and 16.7 (23.5% amino acid difference between alleles. The unexpectedly high levels of DRB allelic diversity in the baiji may partly be attributable to its evolutionary adaptations to the freshwater environment which is regarded to have a higher parasite diversity compared to the marine environment. In addition, balancing selection was found to be the main mechanisms in generating sequence diversity at baiji DRB gene. Considerable sequence variation at the adaptive MHC genes despite of significant loss of neutral genetic variation in baiji genome might suggest that intense selection has overpowered random genetic drift as the main evolutionary forces, which further suggested that the critically endangered or nearly extinct status of the baiji is not an outcome of genetic collapse.

  8. Cooperative Control for Multiple Autonomous Vehicles Using Descriptor Functions

    Directory of Open Access Journals (Sweden)

    Marta Niccolini

    2014-01-01

    Full Text Available The paper presents a novel methodology for the control management of a swarm of autonomous vehicles. The vehicles, or agents, may have different skills, and be employed for different missions. The methodology is based on the definition of descriptor functions that model the capabilities of the single agent and each task or mission. The swarm motion is controlled by minimizing a suitable norm of the error between agents’ descriptor functions and other descriptor functions which models the entire mission. The validity of the proposed technique is tested via numerical simulation, using different task assignment scenarios.

  9. Robustness of Multiple Objective Decision Analysis Preference Functions

    National Research Council Canada - National Science Library

    Klimack, William

    2002-01-01

    .... The impact of these differences was examined to improve implementation efficiency. The robustness of the decision model was examined with respect to the preference functions to reduce the time burden imposed on the decision maker...

  10. Larval serum proteins of the gypsy moth, Lymantria dispar: Allometric changes during development suggest several functions for arylphorin and lipophorin

    International Nuclear Information System (INIS)

    Karpells, S.T.

    1989-01-01

    Storage proteins are the major nutritive intermediates in insects and although the serum storage proteins are relatively well studied, definitive roles for many of them have yet to be established. To further characterize their roles in development and to establish quantitative baselines for future studies, two serum proteins, arylphorin (Ap) and lipophorin (Lp), of the gypsy moth, Lymantria dispar, were studied. Ap and Lp, isolated from larval hemolymph, were partially characterized biochemically and immunologically. Hemolymph concentrations throughout larval development were determined using quantitative immunoelectrophoresis and absolute hemolymph amounts of protein were determined by measuring hemolymph volume. Cyclic fluctuations in hemolymph concentrations of Ap in particular correlated with each molting cycle and an increase in Lp levels just prior to pupation suggest a metamorphic change in the role or demand for the protein. Sexual dimorphism in protein concentrations are explained in part by the sexual dimorphism in the number of larval instars. In fact, an additional instar of Ap accumulation in the female gypsy moth is suggested to compensate for the lack of a female-specific storage protein in this species. The last two days of each instar were found to be the optimum time to sample protein concentration with minimum variance. Allometric relationships among Ap accumulation, Lp accumulation and weight gain were uncovered. Ap labelled with [ 14 C]-N-ethylmaleimide was shown to be incorporated into newly synthesized cuticle and setae during a larval-larval molt. The antiserum developed against L. dispar Ap was used to identify the Ap of Trichoplusia in and study Ap titers in parasitized T. in larvae. The antiserum was also used to determine the immunological relatedness of 5 species of Lepidoptera

  11. Multiple Types of Memory and Everyday Functional Assessment in Older Adults

    Science.gov (United States)

    Beaver, Jenna

    2017-01-01

    Abstract Objective Current proxy measures for assessing everyday functioning (e.g., questionnaires, performance-based measures, and direct observation) show discrepancies in their rating of functional status. The present study investigated the relationship between multiple proxy measures of functional status and content memory (i.e., memory for information), temporal order memory, and prospective memory in an older adult sample. Method A total of 197 community-dwelling older adults who did (n = 45) or did not meet (n = 152) criteria for mild cognitive impairment (MCI), completed six different assessments of functional status (two questionnaires, two performance-based tasks, and two direct observation tasks) as well as experimental measures of content memory, prospective memory, and temporal order memory. Results After controlling for demographics and content memory, the temporal order and prospective memory measures explained a significant amount of variance in all proxy functional status measures. When all variables were entered into the regression analyses, content memory and prospective memory were found to be significant predictors of all measures of functional status, whereas temporal order memory was a significant predictor for the questionnaire and direct observation measures, but not performance-based measures. Conclusion The results suggest that direct observation and questionnaire measures may be able to capture components of everyday functioning that require context and temporal sequencing abilities, such as multi-tasking, that are not as well captured in many current laboratory performance-based measures of functional status. Future research should aim to inform the development and use of maximally effective and valid proxy measures of functional ability. PMID:28334170

  12. Multiple Types of Memory and Everyday Functional Assessment in Older Adults.

    Science.gov (United States)

    Beaver, Jenna; Schmitter-Edgecombe, Maureen

    2017-06-01

    Current proxy measures for assessing everyday functioning (e.g., questionnaires, performance-based measures, and direct observation) show discrepancies in their rating of functional status. The present study investigated the relationship between multiple proxy measures of functional status and content memory (i.e., memory for information), temporal order memory, and prospective memory in an older adult sample. A total of 197 community-dwelling older adults who did (n = 45) or did not meet (n = 152) criteria for mild cognitive impairment (MCI), completed six different assessments of functional status (two questionnaires, two performance-based tasks, and two direct observation tasks) as well as experimental measures of content memory, prospective memory, and temporal order memory. After controlling for demographics and content memory, the temporal order and prospective memory measures explained a significant amount of variance in all proxy functional status measures. When all variables were entered into the regression analyses, content memory and prospective memory were found to be significant predictors of all measures of functional status, whereas temporal order memory was a significant predictor for the questionnaire and direct observation measures, but not performance-based measures. The results suggest that direct observation and questionnaire measures may be able to capture components of everyday functioning that require context and temporal sequencing abilities, such as multi-tasking, that are not as well captured in many current laboratory performance-based measures of functional status. Future research should aim to inform the development and use of maximally effective and valid proxy measures of functional ability. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Multiple Functional Variants in cis Modulate PDYN Expression.

    Science.gov (United States)

    Babbitt, Courtney C; Silverman, Jesse S; Haygood, Ralph; Reininga, Jennifer M; Rockman, Matthew V; Wray, Gregory A

    2010-02-01

    Understanding genetic variation and its functional consequences within cis-regulatory regions remains an important challenge in human genetics and evolution. Here, we present a fine-scale functional analysis of segregating variation within the cis-regulatory region of prodynorphin, a gene that encodes an endogenous opioid precursor with roles in cognition and disease. In order to characterize the functional consequences of segregating variation in cis in a region under balancing selection in different human populations, we examined associations between specific polymorphisms and gene expression in vivo and in vitro. We identified five polymorphisms within the 5' flanking region that affect transcript abundance: a 68-bp repeat recognized in prior studies, as well as two microsatellites and two single nucleotide polymorphisms not previously implicated as functional variants. The impact of these variants on transcription differs by brain region, sex, and cell type, implying interactions between cis genotype and the differentiated state of cells. The effects of individual variants on expression level are not additive in some combinations, implying epistatic interactions between nearby variants. These data reveal an unexpectedly complex relationship between segregating genetic variation and its expression-trait consequences and highlights the importance of close functional scrutiny of natural genetic variation within even relatively well-studied cis-regulatory regions.

  14. The structural and functional differentiation of hair cells in a lizard's basilar papilla suggests an operational principle of amniote cochleas.

    Science.gov (United States)

    Chiappe, M Eugenia; Kozlov, Andrei S; Hudspeth, A J

    2007-10-31

    The hair cells in the mammalian cochlea are of two distinct types. Inner hair cells are responsible for transducing mechanical stimuli into electrical responses, which they forward to the brain through a copious afferent innervation. Outer hair cells, which are thought to mediate the active process that sensitizes and tunes the cochlea, possess a negligible afferent innervation. For every inner hair cell, there are approximately three outer hair cells, so only one-quarter of the hair cells directly deliver information to the CNS. Although this is a surprising feature for a sensory system, the occurrence of a similar innervation pattern in birds and crocodilians suggests that the arrangement has an adaptive value. Using a lizard with highly developed hearing, the tokay gecko, we demonstrate in the present study that the same principle operates in a third major group of terrestrial animals. We propose that the differentiation of hair cells into signaling and amplifying classes reflects incompatible strategies for the optimization of mechanoelectrical transduction and of an active process based on active hair-bundle motility.

  15. Functional Components of Cognitive Impairment in Multiple Sclerosis: A Cross-Sectional Investigation

    Directory of Open Access Journals (Sweden)

    Jordi A. Matias-Guiu

    2017-11-01

    Full Text Available BackgroundCognitive impairment is frequent and disabling in multiple sclerosis (MS. Changes in information processing speed constitute the most important cognitive deficit in MS. However, given the clinical and topographical variability of the disease, cognitive impairment may vary greatly and appear in other forms in addition to slower information processing speed. Our aim was to determine the frequency of cognitive impairment, the principal cognitive domains, and components involved in MS and to identify factors associated with presence of cognitive impairment in these patients in a large series of patients.MethodsCross-sectional study of 311 patients with MS [236 with relapsing-remitting MS (RRMS, 52 with secondary progressive MS (SPMS, and 23 with primary progressive MS (PPMS]. Patients’ cognitive function was assessed with a comprehensive neuropsychological assessment protocol. Patients displaying deficits in 2 or more cognitive domains were considered to have cognitive impairment associated with MS. We conducted a principal component analysis to detect different cognitive patterns by identifying clusters of tests highly correlated to one another.ResultsCognitive impairment was detected in 41.5% of the sample, and it was more frequent in patients with SPMS and PPMS (P = 0.002. Expanded Disability Status Scale scores and education were independent predictors of cognitive impairment. Principal component analysis identified seven clusters: attention and basic executive function (including information processing speed, planning and high-level executive function, verbal memory and language, executive and visuospatial performance time, fatigue-depression, visuospatial function, and basic attention and verbal/visual working memory. Mean scoring of components 2 (high-order executive functioning and 3 (verbal memory-language was higher in patients with RRMS than in those with PPMS (component 2 and SPMS (component 3.ConclusionMS is linked to

  16. The hypocretins/orexins: integrators of multiple physiological functions

    Science.gov (United States)

    Li, Jingcheng; Hu, Zhian; Lecea, Luis

    2014-01-01

    The hypocretins (Hcrts), also known as orexins, are two peptides derived from a single precursor produced in the posterior lateral hypothalamus. Over the past decade, the orexin system has been associated with numerous physiological functions, including sleep/arousal, energy homeostasis, endocrine, visceral functions and pathological states, such as narcolepsy and drug abuse. Here, we review the discovery of Hcrt/orexins and their receptors and propose a hypothesis as to how the orexin system orchestrates these multifaceted physiological functions. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2 PMID:24102345

  17. Multiple sclerosis impairs regional functional connectivity in the cerebellum

    DEFF Research Database (Denmark)

    Dogonowski, Anne-Marie; Andersen, Kasper Winther; Madsen, Kristoffer Hougaard

    2013-01-01

    in the cerebellum in MS. This might be caused by a functional disruption of cortico-ponto-cerebellar and spino-cerebellar inputs, since patients with higher lesion load in the left cerebellar peduncles showed a stronger reduction in cerebellar homogeneity. In patients, two clusters in the left posterior cerebellum...

  18. Tyrosine Residues Regulate Multiple Nuclear Functions of P54nrb.

    Science.gov (United States)

    Lee, Ahn R; Hung, Wayne; Xie, Ning; Liu, Liangliang; He, Leye; Dong, Xuesen

    2017-04-01

    The non-POU-domain-containing octamer binding protein (NONO; also known as p54nrb) has various nuclear functions ranging from transcription, RNA splicing, DNA synthesis and repair. Although tyrosine phosphorylation has been proposed to account for the multi-functional properties of p54nrb, direct evidence on p54nrb as a phosphotyrosine protein remains unclear. To investigate the tyrosine phosphorylation status of p54nrb, we performed site-directed mutagenesis on the five tyrosine residues of p54nrb, replacing the tyrosine residues with phenylalanine or alanine, and immunoblotted for tyrosine phosphorylation. We then preceded with luciferase reporter assays, RNA splicing minigene assays, co-immunoprecipitation, and confocal microscopy to study the function of p54nrb tyrosine residues on transcription, RNA splicing, protein-protein interaction, and cellular localization. We found that p54nrb was not phosphorylated at tyrosine residues. Rather, it has non-specific binding affinity to anti-phosphotyrosine antibodies. However, replacement of tyrosine with phenylalanine altered p54nrb activities in transcription co-repression and RNA splicing in gene context-dependent fashions by means of differential regulation of p54nrb protein association with its interacting partners and co-regulators of transcription and splicing. These results demonstrate that tyrosine residues, regardless of phosphorylation status, are important for p54nrb function. J. Cell. Physiol. 232: 852-861, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. "THE RELATION OF HYPERHOMOCYSTEINEMIA TO COGNITIVE FUNCTION AND BRAIN ATROPHY IN PATIENTS WITH MULTIPLE SCLEROSIS "

    Directory of Open Access Journals (Sweden)

    M. Ghaffarpour

    2007-06-01

    Full Text Available Cognitive impairment may be a common even at the onset of multiple sclerosis (MS. In this case-control study, we tried to find out the probable relationship between homocysteine levels and cerebral atrophy or cognitive impairment in patients with multiple sclerosis. One hundred fifty six patients who had MS according to McDonald diagnostic criteria were included in this study. Patients’ age, gender, and educational level, MS duration and clinical type, disability, cognitive function state based on minimental state examination (MMSE, presence of hyperhomocysteinemia, and brain atrophy were evaluated. There was no statistically significant relationship between hyperhomocysteinemia and cognitive status. Total homocysteine levels had a significant correlation with MMSE score only in those patients with elementary level of education. Also total homocysteine levels and overall cerebral atrophy did not indicate significant relationship according to those independent variables mentioned above except in the patients with EDSS less than 6. When intercaudate ratio > 0.10 was applied as a criterion for cerebral atrophy, we found that hyperhomocysteinemia related significantly to intercaudate ratio > 0.10 in females, aged between 21 and 30 years, MS duration ≤ 5 years, primary progressive MS and relapsing-remitting MS clinical types, EDSS ≤ 3 and elementary level of education. We suggest applying MMSE only for the first step of cognitive function survey. In the next steps, much more exact test must be used (e.g. MSNQ. Also we can not suggest measuring plasma homocysteine level as criterion for monitoring the cognitive function in patients with MS.

  20. Multiple functional units in the preattentive segmentation of speech in Japanese: evidence from word illusions.

    Science.gov (United States)

    Nakamura, Miyoko; Kolinsky, Régine

    2014-12-01

    We explored the functional units of speech segmentation in Japanese using dichotic presentation and a detection task requiring no intentional sublexical analysis. Indeed, illusory perception of a target word might result from preattentive migration of phonemes, morae, or syllables from one ear to the other. In Experiment I, Japanese listeners detected targets presented in hiragana and/or kanji. Phoneme migrations did occur, suggesting that orthography-independent sublexical constituents play some role in segmentation. However, syllable and especially mora migrations were more numerous. This pattern of results was not observed in French speakers (Experiment 2), suggesting that it reflects native segmentation in Japanese. To control for the intervention of kanji representations (many words are written in kanji, and one kanji often corresponds to one syllable), in Experiment 3, Japanese listeners were presented with target loanwords that can be written only in katakana. Again, phoneme migrations occurred, while the first mora and syllable led to similar rates of illusory percepts. No migration occurred for the second, "special" mora (/J/ or/N/), probably because this constitutes the latter part of a heavy syllable. Overall, these findings suggest that multiple units, such as morae, syllables, and even phonemes, function independently of orthographic knowledge in Japanese preattentive speech segmentation.

  1. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  2. New MoM code incorporating multiple domain basis functions

    CSIR Research Space (South Africa)

    Lysko, AA

    2011-08-01

    Full Text Available piecewise linear approximation of geometry. This often leads to an unnecessarily great number of unknowns used to model relatively small loop and spiral antennas, coils and other curved structures. This is because the program creates a dense mesh... to accelerate computation of the elements of the impedance matrix and showed acceleration factor exceeding an order of magnitude, subject to a high accuracy requirement. 3. On Code Functionality and Application Results The package of programs was written...

  3. The multiple roles and functions of English in South Korea

    Directory of Open Access Journals (Sweden)

    Gene Vasilopoulos

    2013-10-01

    Full Text Available In the field of language and identity, the subcategory of gender has been an area of growing interest (Pavlenko, 2001; Norton & Pavlenko, 2004; Menard-Warwick, 2008; and Higgins, 2010. Adopting the view of gender as “a system of social relationships and discursive practices” (Norton & Pavlenko, 2004, p. 504, social context is fundamental in understanding how gender relates to foreign language learning. This qualitative study focused on the extent to which gender impacts English language learning and English language use in the context of teaching English as a foreign language in South Korea. More specifically, it investigates how gender shapes self and social identity, and how these identities relate to English language learning and English language use, at present and/or in the future, in both real and/or imagined communities. Four male and four female participants were selected using purposive homogenous sampling techniques based on the criteria of having lived abroad in an English speaking community for over 5 years—a criterion which assumes the formation of self and social identity in addition to their native Korean L1. Data was collected through multiple methods including open-ended questionnaires, in-depth interviews, and focus group discussions. Interview and questionnaire data reveals gender differences in the symbolic meaning of English language, the relevance of English in self and social positioning, and the role of English in shaping future professional trajectories with males situating themselves in international contexts and females in the local.

  4. Functional Disturbances Within Frontostriatal Circuits Across Multiple Childhood Psychopathologies

    Science.gov (United States)

    Marsh, Rachel; Maia, Tiago V.; Peterson, Bradley S.

    2009-01-01

    Objective Neuroimaging studies of healthy individuals inform us about the normative maturation of the frontostriatal circuits that subserve self-regulatory control processes. Findings from these studies can be used as a reference frame against which to compare the aberrant development of these processes in individuals across a wide range of childhood psychopathologies. Method The authors reviewed extensive neuroimaging evidence for the presence of abnormalities in frontostriatal circuits in children and adults with Tourette’s syndrome and obsessive-compulsive disorder (OCD) as well as a more limited number of imaging studies of adolescents and adults with anorexia nervosa or bulimia nervosa that, together, implicate dysregulation of frontostriatal control systems in the pathogenesis of these eating disorders. Results The presence of an impaired capacity for self-regulatory control that derives from abnormal development of frontostriatal circuits likely interacts in similar ways with normally occurring somatic sensations and motor urges, intrusive thoughts, sensations of hunger, and preoccupation with body shape and weight to contribute, respectively, to the development of the tics of Tourette’s syndrome, the obsessions of OCD, the binge eating behaviors of bulimia, and the self-starvation of anorexia. Conclusions Analogous brain mechanisms in parallel frontostriatal circuits, or even in differing portions of the same frontostriatal circuit, may underlie the differing behavioral disturbances in these multiple disorders, although further research is needed to confirm this hypothesis. PMID:19448188

  5. On Measurement of Efficiency of Cobb-Douglas Production Function with Additive and Multiplicative Errors

    Directory of Open Access Journals (Sweden)

    Md. Moyazzem Hossain

    2015-02-01

    Full Text Available In developing counties, efficiency of economic development has determined by the analysis of industrial production. An examination of the characteristic of industrial sector is an essential aspect of growth studies. The most of the developed countries are highly industrialized as they brief “The more industrialization, the more development”. For proper industrialization and industrial development we have to study industrial input-output relationship that leads to production analysis. For a number of reasons econometrician’s belief that industrial production is the most important component of economic development because, if domestic industrial production increases, GDP will increase, if elasticity of labor is higher, implement rates will increase and investment will increase if elasticity of capital is higher. In this regard, this paper should be helpful in suggesting the most suitable Cobb-Douglas production function to forecast the production process for some selected manufacturing industries of developing countries like Bangladesh. This paper choose the appropriate Cobb-Douglas function which gives optimal combination of inputs, that is, the combination that enables it to produce the desired level of output with minimum cost and hence with maximum profitability for some selected manufacturing industries of Bangladesh over the period 1978-79 to 2011-2012. The estimated results shows that the estimates of both capital and labor elasticity of Cobb-Douglas production function with additive errors are more efficient than those estimates of Cobb-Douglas production function with multiplicative errors.

  6. Ras proteins have multiple functions in vegetative cells of Dictyostelium.

    Science.gov (United States)

    Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

    2010-11-01

    During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG⁻ cells are only partially deficient in chemotaxis, whereas rasC⁻/rasG⁻ cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG⁻, rasC⁻, and rasC⁻/rasG⁻ cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG⁻ and rasC⁻/rasG⁻ cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG⁻ and rasC⁻/rasG⁻ cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells.

  7. A Powerful Test for Comparing Multiple Regression Functions.

    Science.gov (United States)

    Maity, Arnab

    2012-09-01

    In this article, we address the important problem of comparison of two or more population regression functions. Recently, Pardo-Fernández, Van Keilegom and González-Manteiga (2007) developed test statistics for simple nonparametric regression models: Y(ij) = θ(j)(Z(ij)) + σ(j)(Z(ij))∊(ij), based on empirical distributions of the errors in each population j = 1, … , J. In this paper, we propose a test for equality of the θ(j)(·) based on the concept of generalized likelihood ratio type statistics. We also generalize our test for other nonparametric regression setups, e.g, nonparametric logistic regression, where the loglikelihood for population j is any general smooth function [Formula: see text]. We describe a resampling procedure to obtain the critical values of the test. In addition, we present a simulation study to evaluate the performance of the proposed test and compare our results to those in Pardo-Fernández et al. (2007).

  8. Acquisition and processing of multiple functional investigations in cardiology

    International Nuclear Information System (INIS)

    Baruthio, J.; Constantinesco, A.; Chavas, M.; Meyer, P.; Dumitresco, B.; Chambron, J.; Nikitine, S.; Voegtlin, R.

    1978-01-01

    This work is based on a acquisition and pretreating Service of data and signals resulting from several types of functional explorations in cardiology. This Service, through a specialised phone-line, is connected to the Medical Centre of Informatic where the different treatments and on occasion the recording of data are carried out. This functions according to the Real Time Executive System and the clinical results are send back to the investigation unit. The main types of cardiologic analysis as studied by the system are envisaged: measure in real time of the cardiac output and analysis of the radiocardiogram, measure and display of the thoracic potentials, spectral analysis of the vectorcardiogram, quantitative cineangiocardiography and analysis of intracardiac pressures. This system is particularly interesting in that it may treat several processes which could ask for a great capacity of storing and an important calculus power, see for instance the study of thoracic potentials. This type of analysis could not be envisaged financially with isolated calculators. The set of results obtained enables us to investigate thoroughly and precisely the cardiac performance [fr

  9. Validating archetypes for the Multiple Sclerosis Functional Composite.

    Science.gov (United States)

    Braun, Michael; Brandt, Alexander Ulrich; Schulz, Stefan; Boeker, Martin

    2014-08-03

    Numerous information models for electronic health records, such as openEHR archetypes are available. The quality of such clinical models is important to guarantee standardised semantics and to facilitate their interoperability. However, validation aspects are not regarded sufficiently yet. The objective of this report is to investigate the feasibility of archetype development and its community-based validation process, presuming that this review process is a practical way to ensure high-quality information models amending the formal reference model definitions. A standard archetype development approach was applied on a case set of three clinical tests for multiple sclerosis assessment: After an analysis of the tests, the obtained data elements were organised and structured. The appropriate archetype class was selected and the data elements were implemented in an iterative refinement process. Clinical and information modelling experts validated the models in a structured review process. Four new archetypes were developed and publicly deployed in the openEHR Clinical Knowledge Manager, an online platform provided by the openEHR Foundation. Afterwards, these four archetypes were validated by domain experts in a team review. The review was a formalised process, organised in the Clinical Knowledge Manager. Both, development and review process turned out to be time-consuming tasks, mostly due to difficult selection processes between alternative modelling approaches. The archetype review was a straightforward team process with the goal to validate archetypes pragmatically. The quality of medical information models is crucial to guarantee standardised semantic representation in order to improve interoperability. The validation process is a practical way to better harmonise models that diverge due to necessary flexibility left open by the underlying formal reference model definitions.This case study provides evidence that both community- and tool-enabled review processes

  10. Multiple Pesticides Detoxification Function of Maize (Zea mays) GST34.

    Science.gov (United States)

    Li, Dongzhi; Xu, Li; Pang, Sen; Liu, Zhiqian; Zhao, Weisong; Wang, Chengju

    2017-03-08

    ZmGST34 is a maize Tau class GST gene and was found to be differently expressed between two maize cultivars differing in tolerance to herbicide metolachlor. To explore the possible role of ZmGST34 in maize development, the expression pattern and substrate specificity of ZmGST34 were characterized by quantitative RT-PCR and heterologous expression system, respectively. The results indicated that the expression level of ZmGST34 was increased ∼2-5-fold per day during the second-leaf stage of maize seedling. Chloroacetanilide herbicides or phytohormone treatments had no influence on the expression level of ZmGST34, suggesting that ZmGST34 is a constitutively expressed gene in maize seedling. Heterologous expression in Escherichia coli and in Arabidopsis thaliana proved that ZmGST34 can metabolize most chloroacetanilide herbicides and increase tolerance to these herbicides in transgenic Arabidopsis thaliana. The constitutive expression pattern and broad substrate activity of ZmGST34 suggested that this gene may play an important role in maize development in addition to the detoxification of pesticides.

  11. Bisphenol A affects androgen receptor function via multiple mechanisms.

    Science.gov (United States)

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. Published by Elsevier Ireland Ltd.

  12. Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function

    Science.gov (United States)

    Maher, Pamela

    2017-01-01

    It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. PMID:25961687

  13. Mnesic performance and executive functions in patients with multiple sclerosis (MS

    Directory of Open Access Journals (Sweden)

    Isabel Introzzi

    2009-10-01

    Full Text Available The Episodic Memory (EM and the Executive Functions (EF are cognitive areas that are affected in patients with diagnosis of Multiple Sclerosis (MS. Nowadays there exists scarce works destined to explore the infl uence of the EF on measures of mnesic performance in MS. For this reason, we analyze the effect of the EF on the performance in a set of memory measures. We worked with a clinical group (n=36 and with a control group (n=36 compared by age and educational level. The results show that the clinical group obtained significantly low average values in all the mnesic indexes (with exception of recognition and in all the executive measures. All the executive indexes showed significant associations with some of the indexes of mnesic performance. These findings suggest that the problems in the episodic memory in EM patients could be analyzed as the manifestation of a global disorder that could be similar to the one that involves the EF.

  14. Forgotten but Not Gone: Retro-Cue Costs and Benefits in a Double-Cueing Paradigm Suggest Multiple States in Visual Short-Term Memory

    Science.gov (United States)

    van Moorselaar, Dirk; Olivers, Christian N. L.; Theeuwes, Jan; Lamme, Victor A. F.; Sligte, Ilja G.

    2015-01-01

    Visual short-term memory (VSTM) performance is enhanced when the to-be-tested item is cued after encoding. This so-called retro-cue benefit is typically accompanied by a cost for the noncued items, suggesting that information is lost from VSTM upon presentation of a retrospective cue. Here we assessed whether noncued items can be restored to VSTM…

  15. Forgotten but not gone: Retro-cue costs and benefits in a double-cueing paradigm suggest multiple states in visual short-term memory

    NARCIS (Netherlands)

    van Moorselaar, D.; Olivers, C.N.L.; Theeuwes, J.; Lamme, V.A.F.; Sligte, I.G.

    2015-01-01

    Visual short-term memory (VSTM) performance is enhanced when the to-be-tested item is cued after encoding. This so-called retro-cue benefit is typically accompanied by a cost for the noncued items, suggesting that information is lost from VSTM upon presentation of a retrospective cue. Here we

  16. Forgotten but not gone: retro-cue cost and benefits in a double-cueing paradigm suggest multiple states in visual short-term memory

    NARCIS (Netherlands)

    van Moorselaar, D.; Olivers, C.N.L.; Theeuwes, J.; Lamme, V.A.F.; Sligte, I.G.

    2015-01-01

    Visual short-term memory (VSTM) performance is enhanced when the to-be-tested item is cued after encoding. This so-called retro-cue benefit is typically accompanied by a cost for the noncued items, suggesting that information is lost from VSTM upon presentation of a retrospective cue. Here we

  17. Melatonin in Plants - Diversity of Levels and Multiplicity of Functions.

    Science.gov (United States)

    Hardeland, Rüdiger

    2016-01-01

    Melatonin has been detected in numerous plant species. A particularly surprising finding concerns the highly divergent levels of melatonin that vary between species, organs and environmental conditions, from a few pg/g to over 20 μg/g, reportedly up to 200 μg/g. Highest values have been determined in oily seeds and in plant organs exposed to high UV radiation. The divergency of melatonin concentrations is discussed under various functional aspects and focused on several open questions. This comprises differences in precursor availability, catabolism, the relative contribution of isoenzymes of the melatonin biosynthetic pathway, and differences in rate limitation by either serotonin N-acetyltransferase or N-acetylserotonin O-methyltransferase. Other differences are related to the remarkable pleiotropy of melatonin, which exhibits properties as a growth regulator and morphogenetic factor, actually debated in terms of auxin-like effects, and as a signaling molecule that modulates pathways of ethylene, abscisic, jasmonic and salicylic acids and is involved in stress tolerance, pathogen defense and delay of senescence. In the context of high light/UV intensities, elevated melatonin levels exceed those required for signaling via stress-related phytohormones and may comprise direct antioxidant and photoprotectant properties, perhaps with a contribution of its oxidatively formed metabolites, such as N (1)-acetyl-N (2)-formyl-5-methoxykynuramine and its secondary products. High melatonin levels in seeds may also serve antioxidative protection and have been shown to promote seed viability and germination capacity.

  18. Correlates of sexual function in male and female patients with multiple sclerosis.

    Science.gov (United States)

    Lew-Starowicz, Michal; Rola, Rafal

    2014-09-01

    Many factors have been suggested to contribute to sexual dysfunction (SD) in multiple sclerosis (MS) patients, but the research on their impact on sexual functioning (SF) and sexual quality of life (SQoL) remains scant. The aim of this study was to investigate correlates of SF and SQoL in MS patients, as well as possible gender differences. 204 MS patients were interviewed, completed the questionnaires, and underwent neurological assessment. Primary outcome measures included the International Index of Erectile Function, the Female Sexual Function Questionnaire, the Sexual Quality of Life Questionnaire, the Beck Depression Inventory, and the Expanded Disability Status Scale. The course and duration of the disease did not predict patients' SF. Negative correlations were found for brainstem symptoms with orgasmic function and overall satisfaction in men and between cognitive functioning and the partner domain in women. Interestingly, brainstem symptoms correlated positively with the arousal domain in women. More than half (52.1%) of patients fulfilled Beck Depression Inventory criteria for depression, and these patients showed more SD than nondepressive individuals. The strongest negative correlations with depressive symptoms were found for desire, erectile function, and overall satisfaction with sexual life in men and for orgasm and sexual enjoyment in women. Deterioration in particular domains of SF was clearly related with diminished SQoL. The main gender difference was a strong influence of decreased desire on SQoL in women and no such correlation in men. Negative assessment of the relationship with partner significantly affected all domains of SF and SQoL in MS women and the desire domain in MS men. Several correlates of SF in MS patients were found. The role of brainstem symptoms needs further investigation. Clinicians should pay close attention to depressive symptoms and relationship factors in MS patients who suffer from SD. © 2014 International Society for

  19. Function of One Regular Separable Relation Set Decided for the Minimal Covering in Multiple Valued Logic

    Directory of Open Access Journals (Sweden)

    Liu Yu Zhen

    2016-01-01

    Full Text Available Multiple-valued logic is an important branch of the computer science and technology. Multiple-valued logic studies the theory, multiple-valued circuit & multiple-valued system, and the applications of multiple-valued logic included.In the theory of multiple-valued logic, one primary and important problem is the completeness of function sets, which can be solved depending on the decision for all the precomplete sets(also called maximal closed sets of K-valued function sets noted by PK*, and another is the decision for Sheffer function, which can be totally solved by picking out all of the minimal covering of the precomplete sets. In the function structure theory of multi-logic, decision on Sheffer function is an important role. It contains structure and decision of full multi-logic and partial multi-logic. Its decision is closely related to decision of completeness of function which can be done by deciding the minimal covering of full multi-logic and partial-logic. By theory of completeness of partial multi-logic, we prove that function of one regular separable relation is not minimal covering of PK* under the condition of m = 2, σ = e.

  20. Multiple loci associated with renal function in African Americans.

    Directory of Open Access Journals (Sweden)

    Daniel Shriner

    Full Text Available The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR. We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.

  1. Interferon-β treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Frystyk, Jan; Miller, Karen K

    2010-01-01

    We describe a 34-year-old female treated with IFN-ß for 8 years with a biochemical profile suggestive of acromegaly. The patient presented with elevated serum insulin-like growth factor-I (IGF-I) and insufficient suppression of growth hormone (GH) during oral glucose tolerance test (OGTT). There ......-I. In conclusion, IFN-ß treatment mimicked acromegaly biochemically. The changes were partially reversible....

  2. Interferon-β treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Frystyk, Jan; Miller, Karen K

    2010-01-01

    We describe a 34-year-old female treated with IFN-β for 8 years with a biochemical profile suggestive of acromegaly. The patient presented with elevated serum insulin-like growth factor-I (IGF-I) and insufficient suppression of growth hormone (GH) during oral glucose tolerance test (OGTT). There ......-I. In conclusion, IFN-β treatment mimicked acromegaly biochemically. The changes were partially reversible....

  3. Estimation of Multiple Point Sources for Linear Fractional Order Systems Using Modulating Functions

    KAUST Repository

    Belkhatir, Zehor; Laleg-Kirati, Taous-Meriem

    2017-01-01

    This paper proposes an estimation algorithm for the characterization of multiple point inputs for linear fractional order systems. First, using polynomial modulating functions method and a suitable change of variables the problem of estimating

  4. CD21+ (B2 antigen+) cell decrement and CD4+CD29+ (helper-inducer) cell increment suggest an activation of cell immune reactivity in multiple sclerosis.

    Science.gov (United States)

    Gambi, D; Porrini, A M; Giampietro, A; Macor, S

    1991-08-01

    Two-color flow cytometric analysis on peripheral blood lymphocytes of 35 untreated multiple sclerosis (MS) patients, 17 other medical disease (OMD) patients and 14 healthy control (HC) subjects was performed to evaluate the levels of different T and B cell subpopulations. In MS patients we observed an increase in CD4+CD29+ helper-inducer cells but this increase was not related to the different phases of the disease. We hypothesize that this change is related to the reduction of CD21+ cells expressing B2 antigen, a 140 kDa molecule disappearing after B cell activation. An increased level of CD4+CD45RA- (helper-inducer-like cells) and a reduction of CD4+CD29- (suppressor-inducer-like cells) were also present in our patients. These findings demonstrate an immune 'disequilibrium' in MS, which is linked with an increased level of CD25+ cells expressing the interleukin-2 (IL-2) receptor. IL-2, besides being a T cell growth factor, is also a B cell growth factor. These data let us hypothesize that an activation of the immune response is present in MS.

  5. Sequential optimization of matrix chain multiplication relative to different cost functions

    KAUST Repository

    Chikalov, Igor; Hussain, Shahid; Moshkov, Mikhail

    2011-01-01

    In this paper, we present a methodology to optimize matrix chain multiplication sequentially relative to different cost functions such as total number of scalar multiplications, communication overhead in a multiprocessor environment, etc. For n matrices our optimization procedure requires O(n 3) arithmetic operations per one cost function. This work is done in the framework of a dynamic programming extension that allows sequential optimization relative to different criteria. © 2011 Springer-Verlag Berlin Heidelberg.

  6. Forgotten but not gone: Retro-cue costs and benefits in a double-cueing paradigm suggest multiple states in visual short-term memory.

    Science.gov (United States)

    van Moorselaar, Dirk; Olivers, Christian N L; Theeuwes, Jan; Lamme, Victor A F; Sligte, Ilja G

    2015-11-01

    Visual short-term memory (VSTM) performance is enhanced when the to-be-tested item is cued after encoding. This so-called retro-cue benefit is typically accompanied by a cost for the noncued items, suggesting that information is lost from VSTM upon presentation of a retrospective cue. Here we assessed whether noncued items can be restored to VSTM when made relevant again by a subsequent second cue. We presented either 1 or 2 consecutive retro-cues (80% valid) during the retention interval of a change-detection task. Relative to no cue, a valid cue increased VSTM capacity by 2 items, while an invalid cue decreased capacity by 2. Importantly, when a second, valid cue followed an invalid cue, capacity regained 2 items, so that performance was back on par. In addition, when the second cue was also invalid, there was no extra loss of information from VSTM, suggesting that those items that survived a first invalid cue, automatically also survived a second. We conclude that these results are in support of a very versatile VSTM system, in which memoranda adopt different representational states depending on whether they are deemed relevant now, in the future, or not at all. We discuss a neural model that is consistent with this conclusion. (c) 2015 APA, all rights reserved).

  7. Ned-19 inhibition of parasite growth and multiplication suggests a role for NAADP mediated signalling in the asexual development of Plasmodium falciparum.

    Science.gov (United States)

    Suárez-Cortés, Pablo; Gambara, Guido; Favia, Annarita; Palombi, Fioretta; Alano, Pietro; Filippini, Antonio

    2017-09-12

    Although malaria is a preventable and curable human disease, millions of people risk to be infected by the Plasmodium parasites and to develop this illness. Therefore, there is an urgent need to identify new anti-malarial drugs. Ca 2+ signalling regulates different processes in the life cycle of Plasmodium falciparum, representing a suitable target for the development of new drugs. This study investigated for the first time the effect of a highly specific inhibitor of nicotinic acid adenine dinucleotide phosphate (NAADP)-induced Ca 2+ release (Ned-19) on P. falciparum, revealing the inhibitory effect of this compound on the blood stage development of this parasite. Ned-19 inhibits both the transition of the parasite from the early to the late trophozoite stage and the ability of the late trophozoite to develop to the multinucleated schizont stage. In addition, Ned-19 affects spontaneous intracellular Ca 2+ oscillations in ring and trophozoite stage parasites, suggesting that the observed inhibitory effects may be associated to regulation of intracellular Ca 2+ levels. This study highlights the inhibitory effect of Ned-19 on progression of the asexual life cycle of P. falciparum. The observation that Ned-19 inhibits spontaneous Ca 2+ oscillations suggests a potential role of NAADP in regulating Ca 2+ signalling of P. falciparum.

  8. Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

    Science.gov (United States)

    Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

    2012-08-01

    Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

  9. Interferon-beta treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Frystyk, Jan; Miller, K.K.

    2010-01-01

    We describe a 34-year-old female treated with IFN-beta for 8 years with a biochemical profile suggestive of acromegaly. The patient presented with elevated serum insulin-like growth factor-I (IGF-I) and insufficient suppression of growth hormone (GH) during oral glucose tolerance test (OGTT......). There were no clinical features of acromegaly. A 5-day profile showed higher GH levels on the 3 days following IFN-beta injections. Total and bioactive IGF-I were also elevated but did not fluctuate. Four weeks off IFN-beta normalized suppression of GH during OGTT but did not reduce serum IGF-I or bioactive...... IGF-I. In conclusion, IFN-beta treatment mimicked acromegaly biochemically. The changes were partially reversible...

  10. Using multiple schedules during functional communication training to promote rapid transfer of treatment effects.

    Science.gov (United States)

    Fisher, Wayne W; Greer, Brian D; Fuhrman, Ashley M; Querim, Angie C

    2015-12-01

    Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and therapists. With 2 children, we conducted FCT in the context of mixed (baseline) and multiple (treatment) schedules introduced across settings or therapists using a multiple baseline design. Results indicated that when the multiple schedules were introduced, the functional communication response came under rapid discriminative control, and problem behavior remained at near-zero rates. We extended these findings with another individual by using a more traditional baseline in which problem behavior produced reinforcement. Results replicated those of the previous participants and showed rapid reductions in problem behavior when multiple schedules were implemented across settings. © Society for the Experimental Analysis of Behavior.

  11. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    Science.gov (United States)

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  12. Tamsulosin 0.4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction

    NARCIS (Netherlands)

    Höfner, K.; Claes, H.; de Reijke, T. M.; Folkestad, B.; Speakman, M. J.

    1999-01-01

    To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Data from 830 patients randomized into three European

  13. Evolutionary relationships in the sand-dwelling cichlid lineage of lake tanganyika suggest multiple colonization of rocky habitats and convergent origin of biparental mouthbrooding.

    Science.gov (United States)

    Koblmüller, Stephan; Salzburger, Walter; Sturmbauer, Christian

    2004-01-01

    The cichlid species flock of Lake Tanganyika is comprised of seven seeding lineages that evolved in step with changes of the lake environment. One seeding lineage diversified into at least six lineages within a short period of time. Our study focuses on the diversification of one of these lineages, the Ectodini, comprising highly specialized, sand- and rock-dwelling species. They display two distinct breeding styles: maternal and biparental mouthbrooding. By analyzing three mtDNA gene segments in 30 species representing all 13 described genera, we show that the Ectodini rapidly diversified into four clades at the onset of their radiation. The monotypic genus Grammatotria is likely to represent the most ancestral split, followed by the almost contemporary origin of three additional clades, the first comprising the benthic genus Callochromis, the second comprising the benthic genera Asprotilapia, Xenotilapia, Enantiopus, and Microdontochromis, and the third comprising the semi-pelagic genera Ophthalmotilapia, Cardiopharynx, Cyathopharynx, Ectodus, Aulonocranus, Lestradea, and Cunningtonia. Our study confirms the benthic and sand-dwelling life-style as ancestral. Rocky habitats were colonized independently in the Xenotilapia- and Ophthalmotilapia-clade. The Xenotilapia-clade comprises both maternal and biparental mouthbrooders. Their mode of breeding appears to be highly plastic: biparental mouthbrooding either evolved once in the common ancestor of the clade, to be reverted at least three times, or evolved at least five times independently from a maternally mouthbrooding ancestor. Furthermore, the genera Xenotilapia, Microdontochromis, Lestradea, and Ophthalmotilapia appeared paraphyletic in our analyses, suggesting the need of taxonomic revision.

  14. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  15. Reconstruction of an input function from a dynamic PET water image using multiple tissue curves

    Science.gov (United States)

    Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro

    2016-08-01

    Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with {{\\text{H}}2} 15O or C15O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic {{\\text{H}}2} 15O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

  16. Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

    Science.gov (United States)

    Deepak, Kishore K; Al-Umran, Khalid Umran; AI-Sheikh, Mona H; Dkoli, B V; Al-Rubaish, Abdullah

    2015-01-01

    The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines. We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters. We analyzed the effect of varying degree of non-functionality ranging from 0 to 4, on test reliability, difficulty index, discrimination index and point biserial correlation. The non-functionality of distracters inversely affected the test reliability and quality of items in a predictable manner. The non-functioning distracters made the items easier and lowered the discrimination index significantly. Three non-functional distracters in a 5-option MCQ significantly affected all psychometric properties (p psychometrically as effective as 5-option items. Our study reveals that a multiple choice question with 3 functional options provides lower most limit of item format that has adequate psychometric property. The test containing items with less number of functioning options have significantly lower reliability. The distracter function analysis and revision of nonfunctioning distracters can serve as important methods to improve the psychometrics and reliability of assessment.

  17. On functional determinants of matrix differential operators with multiple zero modes

    NARCIS (Netherlands)

    Falco, G.M.; Fedorenko, Andrey A; Gruzberg, Ilya A

    2017-01-01

    We generalize the method of computing functional determinants with a single excluded zero eigenvalue developed by McKane and Tarlie to differential operators with multiple zero eigenvalues. We derive general formulas for such functional determinants of $r\\times r$ matrix second order differential

  18. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    Science.gov (United States)

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  19. Effects of Functional Mobility Skills Training for Adults with Severe Multiple Disabilities

    Science.gov (United States)

    Whinnery, Stacie B.; Whinnery, Keith W.

    2011-01-01

    This study investigated the effects of a functional mobility program on the functional standing and walking skills of five adults with developmental disabilities. The Mobility Opportunities Via Education (MOVE) Curriculum was implemented using a multiple-baseline across subjects design. Repeated measures were taken during baseline, intervention…

  20. Micropatterning of Functional Conductive Polymers with Multiple Surface Chemistries in Register

    DEFF Research Database (Denmark)

    Lind, Johan Ulrik; Acikgöz, Canet; Daugaard, Anders Egede

    2012-01-01

    A versatile procedure is presented for fast and efficient micropatterning of multiple types of covalently bound surface chemistry in perfect register on and between conductive polymer microcircuits. The micropatterning principle is applied to several types of native and functionalized PEDOT (poly(3...... functionalized conjugated polymer systems....

  1. The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

    Science.gov (United States)

    Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

    2013-10-02

    Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

  2. Prospective memory in multiple sclerosis: The impact of cue distinctiveness and executive functioning.

    Science.gov (United States)

    Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

    2016-11-01

    Prospective memory (PM), the ability to remember to do something at the appropriate time in the future, is crucial in everyday life. One way to improve PM performance is to increase the salience of a cue announcing that it is time to act. Multiple sclerosis (MS) patients often report PM failures and there is growing evidence of PM deficits among this population. However, such deficits are poorly characterized and their relation to cognitive status remains unclear. To better understand PM deficits in MS patients, this study investigated the impact of cue salience on PM, and its relation to retrospective memory (RM) and executive deficits. Thirty-nine (39) MS patients were compared to 18 healthy controls on a PM task modulating cue salience during an ongoing general knowledge test. MS patients performed worse than controls on the PM task, regardless of cue salience. MS patients' executive functions contributed significantly to the variance in PM performance, whereas age, education and RM did not. Interestingly, low- and high-executive patients' performance differed when the cue was not salient, but not when it was, suggesting that low-executive MS patients benefited more from cue salience. These findings add to the growing evidence of PM deficits in MS and highlight the contribution of executive functions to certain aspects of PM. In low-executive MS patients, high cue salience improves PM performance by reducing the detection threshold and need for environmental monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Functional genomic analysis supports conservation of function among cellulose synthase-like a gene family members and suggests diverse roles of mannans in plants

    DEFF Research Database (Denmark)

    Liepman, Aaron H; Nairn, C Joseph; Willats, William G T

    2007-01-01

    from Arabidopsis (Arabidopsis thaliana), guar (Cyamopsis tetragonolobus), and Populus trichocarpa catalyze beta-1,4-mannan and glucomannan synthase reactions in vitro. Mannan polysaccharides and homologs of CslA genes appear to be present in all lineages of land plants analyzed to date. In many plants......, the CslA genes are members of extended multigene families; however, it is not known whether all CslA proteins are glucomannan synthases. CslA proteins from diverse land plant species, including representatives of the mono- and dicotyledonous angiosperms, gymnosperms, and bryophytes, were produced...... they are prevalent at cell junctions and in buds. Taken together, these results demonstrate that members of the CslA gene family from diverse plant species encode glucomannan synthases and support the hypothesis that mannans function in metabolic networks devoted to other cellular processes in addition to cell wall...

  4. Curvelet-domain multiple matching method combined with cubic B-spline function

    Science.gov (United States)

    Wang, Tong; Wang, Deli; Tian, Mi; Hu, Bin; Liu, Chengming

    2018-05-01

    Since the large amount of surface-related multiple existed in the marine data would influence the results of data processing and interpretation seriously, many researchers had attempted to develop effective methods to remove them. The most successful surface-related multiple elimination method was proposed based on data-driven theory. However, the elimination effect was unsatisfactory due to the existence of amplitude and phase errors. Although the subsequent curvelet-domain multiple-primary separation method achieved better results, poor computational efficiency prevented its application. In this paper, we adopt the cubic B-spline function to improve the traditional curvelet multiple matching method. First, select a little number of unknowns as the basis points of the matching coefficient; second, apply the cubic B-spline function on these basis points to reconstruct the matching array; third, build constraint solving equation based on the relationships of predicted multiple, matching coefficients, and actual data; finally, use the BFGS algorithm to iterate and realize the fast-solving sparse constraint of multiple matching algorithm. Moreover, the soft-threshold method is used to make the method perform better. With the cubic B-spline function, the differences between predicted multiple and original data diminish, which results in less processing time to obtain optimal solutions and fewer iterative loops in the solving procedure based on the L1 norm constraint. The applications to synthetic and field-derived data both validate the practicability and validity of the method.

  5. DMPD: Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17070092 Suppressor of cytokine signaling (SOCS) 2, a protein with multiple function...Epub 2006 Oct 27. (.png) (.svg) (.html) (.csml) Show Suppressor of cytokine signaling (SOCS) 2, a protein with multiple function...SOCS) 2, a protein with multiple functions. Authors Rico-Bautista E, Flores-Morales A, Fernandez-Perez L. Pu

  6. Availability of thermodynamic system with multiple performance parameters based on vector-universal generating function

    International Nuclear Information System (INIS)

    Cai Qi; Shang Yanlong; Chen Lisheng; Zhao Yuguang

    2013-01-01

    Vector-universal generating function was presented to analyze the availability of thermodynamic system with multiple performance parameters. Vector-universal generating function of component's performance was defined, the arithmetic model based on vector-universal generating function was derived for the thermodynamic system, and the calculation method was given for state probability of multi-state component. With the stochastic simulation of the degeneration trend of the multiple factors, the system availability with multiple performance parameters was obtained under composite factors. It is shown by an example that the results of the availability obtained by the binary availability analysis method are somewhat conservative, and the results considering parameter failure based on vector-universal generating function reflect the operation characteristics of the thermodynamic system better. (authors)

  7. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H

    2009-01-01

    randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes...

  8. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue

    OpenAIRE

    Emma Rosalie Driehuis; Lizanne Eva van den Akker; Vincent de Groot; Heleen Beckerman

    2018-01-01

    Objective: To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. Design: A cross-sectional study. Patients: Sixty-two participants with multiple sclerosis-related fatigue. Methods: Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ...

  9. Correlation functions with fusion-channel multiplicity in W3 Toda field theory

    International Nuclear Information System (INIS)

    Belavin, Vladimir; Estienne, Benoit; Foda, Omar; Santachiara, Raoul

    2016-01-01

    Current studies of W N Toda field theory focus on correlation functions such that the W N highest-weight representations in the fusion channels are multiplicity-free. In this work, we study W 3 Toda 4-point functions with multiplicity in the fusion channel. The conformal blocks of these 4-point functions involve matrix elements of a fully-degenerate primary field with a highest-weight in the adjoint representation of sl 3 , and a fully-degenerate primary field with a highest-weight in the fundamental representation of sl 3 . We show that, when the fusion rules do not involve multiplicities, the matrix elements of the fully-degenerate adjoint field, between two arbitrary descendant states, can be computed explicitly, on equal footing with the matrix elements of the semi-degenerate fundamental field. Using null-state conditions, we obtain a fourth-order Fuchsian differential equation for the conformal blocks. Using Okubo theory, we show that, due to the presence of multiplicities, this differential equation belongs to a class of Fuchsian equations that is different from those that have appeared so far in W N theories. We solve this equation, compute its monodromy group, and construct the monodromy-invariant correlation functions. This computation shows in detail how the ambiguities that are caused by the presence of multiplicities are fixed by requiring monodromy-invariance.

  10. Correlation functions with fusion-channel multiplicity in W{sub 3} Toda field theory

    Energy Technology Data Exchange (ETDEWEB)

    Belavin, Vladimir [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky Avenue 53, 119991 Moscow (Russian Federation); Department of Quantum Physics, Institute for Information Transmission Problems,Bolshoy Karetny per. 19, 127994 Moscow (Russian Federation); Estienne, Benoit [LPTHE, CNRS and Université Pierre et Marie Curie,Sorbonne Universités, 4 Place Jussieu, 75252 Paris Cedex 05 (France); Foda, Omar [School of Mathematics and Statistics, University of Melbourne,Parkville, Victoria 3010 (Australia); Santachiara, Raoul [LPTMS, CNRS (UMR 8626), Université Paris-Saclay,15 rue Georges Clémenceau, 91405 Orsay (France)

    2016-06-22

    Current studies of W{sub N} Toda field theory focus on correlation functions such that the W{sub N} highest-weight representations in the fusion channels are multiplicity-free. In this work, we study W{sub 3} Toda 4-point functions with multiplicity in the fusion channel. The conformal blocks of these 4-point functions involve matrix elements of a fully-degenerate primary field with a highest-weight in the adjoint representation of sl{sub 3}, and a fully-degenerate primary field with a highest-weight in the fundamental representation of sl{sub 3}. We show that, when the fusion rules do not involve multiplicities, the matrix elements of the fully-degenerate adjoint field, between two arbitrary descendant states, can be computed explicitly, on equal footing with the matrix elements of the semi-degenerate fundamental field. Using null-state conditions, we obtain a fourth-order Fuchsian differential equation for the conformal blocks. Using Okubo theory, we show that, due to the presence of multiplicities, this differential equation belongs to a class of Fuchsian equations that is different from those that have appeared so far in W{sub N} theories. We solve this equation, compute its monodromy group, and construct the monodromy-invariant correlation functions. This computation shows in detail how the ambiguities that are caused by the presence of multiplicities are fixed by requiring monodromy-invariance.

  11. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Freedman, Mark S; Polman, Chris H

    2009-01-01

    with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon...... index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment...

  12. Predicting Multiple Functions of Sustainable Flood Retention Basins under Uncertainty via Multi-Instance Multi-Label Learning

    Directory of Open Access Journals (Sweden)

    Qinli Yang

    2015-03-01

    Full Text Available The ambiguity of diverse functions of sustainable flood retention basins (SFRBs may lead to conflict and risk in water resources planning and management. How can someone provide an intuitive yet efficient strategy to uncover and distinguish the multiple potential functions of SFRBs under uncertainty? In this study, by exploiting both input and output uncertainties of SFRBs, the authors developed a new data-driven framework to automatically predict the multiple functions of SFRBs by using multi-instance multi-label (MIML learning. A total of 372 sustainable flood retention basins, characterized by 40 variables associated with confidence levels, were surveyed in Scotland, UK. A Gaussian model with Monte Carlo sampling was used to capture the variability of variables (i.e., input uncertainty, and the MIML-support vector machine (SVM algorithm was subsequently applied to predict the potential functions of SFRBs that have not yet been assessed, allowing for one basin belonging to different types (i.e., output uncertainty. Experiments demonstrated that the proposed approach enables effective automatic prediction of the potential functions of SFRBs (e.g., accuracy >93%. The findings suggest that the functional uncertainty of SFRBs under investigation can be better assessed in a more comprehensive and cost-effective way, and the proposed data-driven approach provides a promising method of doing so for water resources management.

  13. Analysis of Multiple Spurious Operation Scenarios for Decay Heat Removal Function of CANDU Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Youngseung; Bae, Yeon-kyoung; Kim, Myungsu [KHNP CRI, Daejeon (Korea, Republic of)

    2016-10-15

    The worst fire broke out in the Browns Ferry Nuclear Power Plant on March 22, 1975. A fire occurrence in a nuclear power plant has recognized a latently serious incident. Nuclear power plants should achieve and maintain the safe shutdown conditions during and after the occurrence of a fire. Functions of the safe shutdown are five such as the shutdown function, the decay heat removal function, the containment function, monitoring and control function, and the supporting function for CANDU type reactors. The purpose of this paper is to analyze that the decay heat removal function of the safe shutdown functions for CANDU type reactors is achieved under the fire induced multiple spurious operation. The scenarios of the fire induced multiple spurious operations (MSO) for the systems used for the decay heat cooling were analyzed. Additionally, Integrated Severe Accident Analysis code for CANDU plants (ISAAC) for determining success criteria of thermal hydraulic analysis was used. Decay heat cooling systems of CANDU reactors are the auxiliary feedwater system, the emergency water supply system, and the shutdown cooling system. A big fire can threat the safety of nuclear power plants, and safe shutdown conditions. The regulatory body in Korea requires the fire hazard analysis including fire induced MSOs. The safe shutdown functions for CANDU reactors are the shutdown function, the decay heat removal function, the containment function, the monitoring and control function, and the supporting service function. The number of spurious operations for the auxiliary feedwater system is more than six and that for the emergency water supply system is one. Additionally, misoperations for the shutdown cooling system are more than two. Accordingly, if total nine components could be spuriously operated, the decay heat removal function would be lost entirely.

  14. Analysis of Multiple Spurious Operation Scenarios for Decay Heat Removal Function of CANDU Reactors

    International Nuclear Information System (INIS)

    Lee, Youngseung; Bae, Yeon-kyoung; Kim, Myungsu

    2016-01-01

    The worst fire broke out in the Browns Ferry Nuclear Power Plant on March 22, 1975. A fire occurrence in a nuclear power plant has recognized a latently serious incident. Nuclear power plants should achieve and maintain the safe shutdown conditions during and after the occurrence of a fire. Functions of the safe shutdown are five such as the shutdown function, the decay heat removal function, the containment function, monitoring and control function, and the supporting function for CANDU type reactors. The purpose of this paper is to analyze that the decay heat removal function of the safe shutdown functions for CANDU type reactors is achieved under the fire induced multiple spurious operation. The scenarios of the fire induced multiple spurious operations (MSO) for the systems used for the decay heat cooling were analyzed. Additionally, Integrated Severe Accident Analysis code for CANDU plants (ISAAC) for determining success criteria of thermal hydraulic analysis was used. Decay heat cooling systems of CANDU reactors are the auxiliary feedwater system, the emergency water supply system, and the shutdown cooling system. A big fire can threat the safety of nuclear power plants, and safe shutdown conditions. The regulatory body in Korea requires the fire hazard analysis including fire induced MSOs. The safe shutdown functions for CANDU reactors are the shutdown function, the decay heat removal function, the containment function, the monitoring and control function, and the supporting service function. The number of spurious operations for the auxiliary feedwater system is more than six and that for the emergency water supply system is one. Additionally, misoperations for the shutdown cooling system are more than two. Accordingly, if total nine components could be spuriously operated, the decay heat removal function would be lost entirely

  15. A diet based on multiple functional concepts improves cardiometabolic risk parameters in healthy subjects

    Directory of Open Access Journals (Sweden)

    Tovar Juscelino

    2012-04-01

    Full Text Available Abstract Background Different foods can modulate cardiometabolic risk factors in persons already affected by metabolic alterations. The objective of this study was to assess, in healthy overweight individuals, the impact of a diet combining multiple functional concepts on risk markers associated with cardiometabolic diseases (CMD. Methods Fourty-four healthy women and men (50-73 y.o, BMI 25-33, fasting glycemia ≤ 6.1 mmol/L participated in a randomized crossover intervention comparing a multifunctional (active diet (AD with a control diet (CD devoid of the "active" components. Each diet was consumed during 4 wk with a 4 wk washout period. AD included the following functional concepts: low glycemic impact meals, antioxidant-rich foods, oily fish as source of long-chain omega-3 fatty acids, viscous dietary fibers, soybean and whole barley kernel products, almonds, stanols and a probiotic strain (Lactobacillus plantarum Heal19/DSM15313. Results Although the aim was to improve metabolic markers without promoting body weight loss, minor weight reductions were observed with both diets (0.9-1.8 ± 0.2%; P P P P = 0.0056, LDL/HDL (-27 ± 2%; P P 1c (-2 ± 0.4%; P = 0.0013, hs-CRP (-29 ± 9%; P = 0.0497 and systolic blood pressure (-8 ± 1%¸ P = 0.0123. The differences remained significant after adjustment for weight change. After AD, the Framingham cardiovascular risk estimate was 30 ± 4% (P P Conclusion The improved biomarker levels recorded in healthy individuals following the multifunctional regime suggest preventive potential of this dietary approach against CMD.

  16. Validity and Reliability of Scores Obtained on Multiple-Choice Questions: Why Functioning Distractors Matter

    Science.gov (United States)

    Ali, Syed Haris; Carr, Patrick A.; Ruit, Kenneth G.

    2016-01-01

    Plausible distractors are important for accurate measurement of knowledge via multiple-choice questions (MCQs). This study demonstrates the impact of higher distractor functioning on validity and reliability of scores obtained on MCQs. Freeresponse (FR) and MCQ versions of a neurohistology practice exam were given to four cohorts of Year 1 medical…

  17. Accounting for multiple functions in environmental life cycle assessment of storm water management solutions

    DEFF Research Database (Denmark)

    Brudler, Sarah; Arnbjerg-Nielsen, Karsten; Rygaard, Martin

    The wide range of approaches to handle storm water runoff have varying effects on the environment. Local stormwater control measures for retention and treatment are increasingly used components in urban climate adaptation plans. Often, these solutions modify the multiple functions of urban...

  18. Multiple Sclerosis and Employment: A Research Review Based on the International Classification of Function

    Science.gov (United States)

    Frain, Michael P.; Bishop, Malachy; Rumrill, Phillip D., Jr.; Chan, Fong; Tansey, Timothy N.; Strauser, David; Chiu, Chung-Yi

    2015-01-01

    Multiple sclerosis (MS) is an unpredictable, sometimes progressive chronic illness affecting people in the prime of their working lives. This article reviews the effects of MS on employment based on the World Health Organization's International Classification of Functioning, Disability and Health model. Correlations between employment and…

  19. Embedding multiple self-organisation functionalities in future radio access networks

    NARCIS (Netherlands)

    Jansen, T.; Amirijoo, M.; Türke, U.; Jorguseski, L.; Zetterberg, K.; Nascimento, J.R.V. do; Schmelz, L.C.; Turk, J.; Balan, I.

    2009-01-01

    Wireless network operators today allocate considerable manual effort in managing their networks. A viable solution for lowering the manual effort is to introduce self-organisation functionalities. In this paper we discuss the challenges that are encountered when embedding multiple self-organisation

  20. Stepwise Analysis of Differential Item Functioning Based on Multiple-Group Partial Credit Model.

    Science.gov (United States)

    Muraki, Eiji

    1999-01-01

    Extended an Item Response Theory (IRT) method for detection of differential item functioning to the partial credit model and applied the method to simulated data using a stepwise procedure. Then applied the stepwise DIF analysis based on the multiple-group partial credit model to writing trend data from the National Assessment of Educational…

  1. Disruption of Structural and Functional Networks in Long-Standing Multiple Sclerosis

    NARCIS (Netherlands)

    Tewarie, P.; Steenwijk, M.D.; Tijms, B.M.; Daams, M.; Balk, L.J.; Stam, C.J.; Uitdehaag, B.M.J.; Polman, C.H.; Geurts, J.J.G.; Barkhof, F.; Pouwels, P.J.W.; Vrenken, H.; Hillebrand, A.

    2014-01-01

    Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter

  2. Transfer functions of double- and multiple-cavity Fabry-Perot filters driven by Lorentzian sources.

    Science.gov (United States)

    Marti, J; Capmany, J

    1996-12-20

    We derive expressions for the transfer functions of double- and multiple-cavity Fabry-Perot filters driven by laser sources with Lorentzian spectrum. These are of interest because of their applications in sensing and channel filtering in optical frequency-division multiplexing networks.

  3. Using Multiple Schedules during Functional Communication Training to Promote Rapid Transfer of Treatment Effects

    Science.gov (United States)

    Fisher, Wayne W.; Greer, Brian D.; Fuhrman, Ashley M.; Querim, Angie C.

    2015-01-01

    Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and…

  4. Langevin dynamics for vector variables driven by multiplicative white noise: A functional formalism

    Science.gov (United States)

    Moreno, Miguel Vera; Arenas, Zochil González; Barci, Daniel G.

    2015-04-01

    We discuss general multidimensional stochastic processes driven by a system of Langevin equations with multiplicative white noise. In particular, we address the problem of how time reversal diffusion processes are affected by the variety of conventions available to deal with stochastic integrals. We present a functional formalism to build up the generating functional of correlation functions without any type of discretization of the Langevin equations at any intermediate step. The generating functional is characterized by a functional integration over two sets of commuting variables, as well as Grassmann variables. In this representation, time reversal transformation became a linear transformation in the extended variables, simplifying in this way the complexity introduced by the mixture of prescriptions and the associated calculus rules. The stochastic calculus is codified in our formalism in the structure of the Grassmann algebra. We study some examples such as higher order derivative Langevin equations and the functional representation of the micromagnetic stochastic Landau-Lifshitz-Gilbert equation.

  5. The Usefulness of Multilevel Hash Tables with Multiple Hash Functions in Large Databases

    Directory of Open Access Journals (Sweden)

    A.T. Akinwale

    2009-05-01

    Full Text Available In this work, attempt is made to select three good hash functions which uniformly distribute hash values that permute their internal states and allow the input bits to generate different output bits. These functions are used in different levels of hash tables that are coded in Java Programming Language and a quite number of data records serve as primary data for testing the performances. The result shows that the two-level hash tables with three different hash functions give a superior performance over one-level hash table with two hash functions or zero-level hash table with one function in term of reducing the conflict keys and quick lookup for a particular element. The result assists to reduce the complexity of join operation in query language from O( n2 to O( 1 by placing larger query result, if any, in multilevel hash tables with multiple hash functions and generate shorter query result.

  6. IMPROVING FUNCTIONAL INDEPENDENCE OF PATIENTS WITH MULTIPLE SCLEROSIS BY PHYSICAL THERAPY AND OCCUPATIONAL THERAPY

    Directory of Open Access Journals (Sweden)

    Ana-Maria Ticărat

    2011-06-01

    Full Text Available Introduction. Patients with multiple sclerosis can have a normal life despite of their real or possible disability and of the progressive nature of it. Scope. Patients who follow physical therapy and occupational therapy will have an increased quality of life and a greater functional independence.Methods. The randomized study was made on 7 patients with multiple sclerosis, from Oradea Day Centre, 3 times/week, ages between 35 – 55 years, functional level between mild and sever. Assessment and rehabilitation methods: inspection, BARTHEL Index. Frenkel method, brething exercises, weights exercises, gait exercises, writind exercises and games were used in the rehabilitation process. Group therapies: sociotherapy, arttherapy, music therapy. Results analysis consisted of the comparison of baseline and final means.Results. By analizing baseline and final means for Barthel Index for each functon separately, it was shown a mild improvement of functional independence for almost assessed functions, with at least 1-1,5 points.Conclusions. Persons with multiple sclerosis who follow physical therapy and occupational therapy presents a better functional independence after the treatment.

  7. Method of Fusion Diagnosis for Dam Service Status Based on Joint Distribution Function of Multiple Points

    Directory of Open Access Journals (Sweden)

    Zhenxiang Jiang

    2016-01-01

    Full Text Available The traditional methods of diagnosing dam service status are always suitable for single measuring point. These methods also reflect the local status of dams without merging multisource data effectively, which is not suitable for diagnosing overall service. This study proposes a new method involving multiple points to diagnose dam service status based on joint distribution function. The function, including monitoring data of multiple points, can be established with t-copula function. Therefore, the possibility, which is an important fusing value in different measuring combinations, can be calculated, and the corresponding diagnosing criterion is established with typical small probability theory. Engineering case study indicates that the fusion diagnosis method can be conducted in real time and the abnormal point can be detected, thereby providing a new early warning method for engineering safety.

  8. Resistance training improves muscle strength and functional capacity in multiple sclerosis

    DEFF Research Database (Denmark)

    Dalgas, U; Stenager, E; Jakobsen, J

    2009-01-01

    strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity. Level of evidence: The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle......OBJECTIVE: To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether the improvements are maintained after the trial. METHODS: The present study was a 2-arm...... and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score...

  9. Disease load at conception predicts survival in later epidemics in a historical French-Canadian cohort, suggesting functional trans-generational effects in humans.

    Directory of Open Access Journals (Sweden)

    Kai Willführ

    Full Text Available OBJECTIVE: Functional trans-generational and parental effects are potentially important determinants of health in several mammals. For humans, the existing evidence is weak. We investigate whether disease exposure triggers functional trans-generational response effects among humans by analyzing siblings who were conceived under different disease loads, and comparing their mortality in later epidemics. Under functional trans-generational response mechanisms, we expect that those who were conceived under high pathogenic stress load will have relatively low mortality during a later epidemic. METHODS: We use data from the Registre de la Population du Québec Ancien, which covers the historical population living in St. Lawrence Valley, Québec, Canada. Children born in 1705-1724 were grouped according to their exposure during conception to the measles 1714-15 epidemic. The 1714-15 epidemic was followed by two mortality crises in 1729-1734. The cause of the first crises in 1729 is not exactly known. The second crisis in 1732 was caused by a smallpox epidemic. Using proportional hazard Cox regression models with multivariate adjustment and with fixed-effects approach that compare siblings, we analyze whether mortality in 1729-1734 is affected by exposure to the 1714-15 epidemic. RESULTS: Children who were conceived during the peak of the measles epidemic of 1714-15 exhibited significantly lower mortality during the 1729-1734 crisis than those who were born before the 1714-15 epidemic (mortality hazard ratio 0.106, p<.05 in multivariate adjusted models; 0.142 p<.1 in sibling comparison models. CONCLUSIONS: The results are consistent with a trans-generational mechanism that functionally responds to pathogen stress and suggest that early disease exposure may be protective later in life. Alternative explanations for the mortality patterns are discussed and shown to be problematic.

  10. Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

    Science.gov (United States)

    Lewis, Brian A

    2010-01-15

    The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

  11. Characterizing functional connectivity during rest in multiple sclerosis patients versus healthy volunteers using independent component analysis

    Energy Technology Data Exchange (ETDEWEB)

    Palacio Garcia, L.; Andrzejak, R.; Prchkovska, V.; Rodrigues, P.

    2016-07-01

    It is commonly thought that our brain is not active when it does not receive any external input. However, during rest, there are still certain distant regions of the brain that are functionally correlated between them: the so-called resting-state networks. This functional connectivity of the brain is disrupted in many neurological diseases. In particular, it has been shown that one of the most studied resting-state networks (the default-mode network) is affected in multiple sclerosis, which is the most common disabling neurological condition affecting the central nervous system of young adults. In this work, I focus on the study of the differences in the resting-state networks between multiple sclerosis patients and healthy volunteers. In order to study the effects of multiple sclerosis on the functional connectivity of the brain, a numerical method known as independent component analysis (ICA) is applied. This technique divides the resting-state fMRI data into independent components. Nonetheless, noise, which could be due to head motion or physiological artifacts, may corrupt the data by indicating a false activation. Therefore, I create a web user interface that allows the user to manually classify all the independent components for a given subject. Eventually, the components classified as noise should be removed from the functional data in order to prevent them from taking part in any further analysis. (Author)

  12. Atom localization and center-of-mass wave-function determination via multiple simultaneous quadrature measurements

    International Nuclear Information System (INIS)

    Evers, Joerg; Qamar, Shahid; Zubairy, M. Suhail

    2007-01-01

    We discuss localization and center-of-mass wave-function measurement of a quantum particle using multiple simultaneous dispersive interactions of the particle with different standing-wave fields. In particular, we consider objects with an internal structure consisting of a single ground state and several excited states. The transitions between ground and the corresponding excited states are coupled to the light fields in the dispersive limit, thus giving rise to a phase shift of the light field during the interaction. We show that multiple simultaneous measurements allow both an increase in the measurement or localization precision in a single direction and the performance of multidimensional measurements or localization. Further, we show that multiple measurements may relax the experimental requirements for each individual measurement

  13. Advanced correlation grid: Analysis and visualisation of functional connectivity among multiple spike trains.

    Science.gov (United States)

    Masud, Mohammad Shahed; Borisyuk, Roman; Stuart, Liz

    2017-07-15

    This study analyses multiple spike trains (MST) data, defines its functional connectivity and subsequently visualises an accurate diagram of connections. This is a challenging problem. For example, it is difficult to distinguish the common input and the direct functional connection of two spike trains. The new method presented in this paper is based on the traditional pairwise cross-correlation function (CCF) and a new combination of statistical techniques. First, the CCF is used to create the Advanced Correlation Grid (ACG) correlation where both the significant peak of the CCF and the corresponding time delay are used for detailed analysis of connectivity. Second, these two features of functional connectivity are used to classify connections. Finally, the visualization technique is used to represent the topology of functional connections. Examples are presented in the paper to demonstrate the new Advanced Correlation Grid method and to show how it enables discrimination between (i) influence from one spike train to another through an intermediate spike train and (ii) influence from one common spike train to another pair of analysed spike trains. The ACG method enables scientists to automatically distinguish between direct connections from spurious connections such as common source connection and indirect connection whereas existing methods require in-depth analysis to identify such connections. The ACG is a new and effective method for studying functional connectivity of multiple spike trains. This method can identify accurately all the direct connections and can distinguish common source and indirect connections automatically. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Combining Shigella Tn-seq data with gold-standard E. coli gene deletion data suggests rare transitions between essential and non-essential gene functionality.

    Science.gov (United States)

    Freed, Nikki E; Bumann, Dirk; Silander, Olin K

    2016-09-06

    Gene essentiality - whether or not a gene is necessary for cell growth - is a fundamental component of gene function. It is not well established how quickly gene essentiality can change, as few studies have compared empirical measures of essentiality between closely related organisms. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in the bacterial pathogen Shigella flexneri 2a 2457T on a genome-wide scale. Superficial analysis of this data suggested that 481 protein-coding genes in this Shigella strain are critical for robust cellular growth on rich media. Comparison of this set of genes with a gold-standard data set of essential genes in the closely related Escherichia coli K12 BW25113 revealed that an excessive number of genes appeared essential in Shigella but non-essential in E. coli. Importantly, and in converse to this comparison, we found no genes that were essential in E. coli and non-essential in Shigella, implying that many genes were artefactually inferred as essential in Shigella. Controlling for such artefacts resulted in a much smaller set of discrepant genes. Among these, we identified three sets of functionally related genes, two of which have previously been implicated as critical for Shigella growth, but which are dispensable for E. coli growth. The data presented here highlight the small number of protein coding genes for which we have strong evidence that their essentiality status differs between the closely related bacterial taxa E. coli and Shigella. A set of genes involved in acetate utilization provides a canonical example. These results leave open the possibility of developing strain-specific antibiotic treatments targeting such differentially essential genes, but suggest that such opportunities may be rare in closely related bacteria.

  15. Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion.

    Science.gov (United States)

    Hogarth, Marshall W; Garton, Fleur C; Houweling, Peter J; Tukiainen, Taru; Lek, Monkol; Macarthur, Daniel G; Seto, Jane T; Quinlan, Kate G R; Yang, Nan; Head, Stewart I; North, Kathryn N

    2016-03-01

    A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ∼ 18% of the global population. There is no associated disease phenotype, but α-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of α-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of α-actinin-3 expression level by comparing the muscle phenotypes of Actn3(+/-) (HET) mice to Actn3(+/+) [wild-type (WT)] and Actn3(-/-) [knockout (KO)] littermates. We show reduction in α-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of α-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z-line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Structural networks involved in attention and executive functions in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Sara Llufriu

    2017-01-01

    Full Text Available Attention and executive deficits are disabling symptoms in multiple sclerosis (MS that have been related to disconnection mechanisms. We aimed to investigate changes in structural connectivity in MS and their association with attention and executive performance applying an improved framework that combines high order probabilistic tractography and anatomical exclusion criteria postprocessing. We compared graph theory metrics of structural networks and fractional anisotropy (FA of white matter (WM connections or edges between 72 MS subjects and 38 healthy volunteers (HV and assessed their correlation with cognition. Patients displayed decreased network transitivity, global efficiency and increased path length compared with HV (p < 0.05, corrected. Also, nodal strength was decreased in 26 of 84 gray matter regions. The distribution of nodes with stronger connections or hubs of the network was similar among groups except for the right pallidum and left insula, which became hubs in patients. MS subjects presented reduced edge FA widespread in the network, while FA was increased in 24 connections (p < 0.05, corrected. Decreased integrity of frontoparietal networks, deep gray nuclei and insula correlated with worse attention and executive performance (r between 0.38 and 0.55, p < 0.05, corrected. Contrarily, higher strength in the right transverse temporal cortex and increased FA of several connections (mainly from cingulate, frontal and occipital cortices were associated with worse functioning (r between −0.40 and −0.47, p < 0.05 corrected. In conclusion, structural brain connectivity is disturbed in MS due to widespread impairment of WM connections and gray matter structures. The increased edge connectivity suggests the presence of reorganization mechanisms at the structural level. Importantly, attention and executive performance relates to frontoparietal networks, deep gray nuclei and insula. These results support the relevance of

  17. Competing failure analysis in phased-mission systems with multiple functional dependence groups

    International Nuclear Information System (INIS)

    Wang, Chaonan; Xing, Liudong; Peng, Rui; Pan, Zhusheng

    2017-01-01

    A phased-mission system (PMS) involves multiple, consecutive, non-overlapping phases of operation. The system structure function and component failure behavior in a PMS can change from phase to phase, posing big challenges to the system reliability analysis. Further complicating the problem is the functional dependence (FDEP) behavior where the failure of certain component(s) causes other component(s) to become unusable or inaccessible or isolated. Previous studies have shown that FDEP can cause competitions between failure propagation and failure isolation in the time domain. While such competing failure effects have been well addressed in single-phase systems, only little work has focused on PMSs with a restrictive assumption that a single FDEP group exists in one phase of the mission. Many practical systems (e.g., computer systems and networks), however may involve multiple FDEP groups during the mission. Moreover, different FDEP groups can be dependent due to sharing some common components; they may appear in a single phase or multiple phases. This paper makes new contributions by modeling and analyzing reliability of PMSs subject to multiple FDEP groups through a Markov chain-based methodology. Propagated failures with both global and selective effects are considered. Four case studies are presented to demonstrate application of the proposed method. - Highlights: • Reliability of phased-mission systems subject to competing failure propagation and isolation effects is modeled. • Multiple independent or dependent functional dependence groups are considered. • Propagated failures with global effects and selective effects are studied. • Four case studies demonstrate generality and application of the proposed Markov-based method.

  18. Impacts of medical treatments for lower urinary tract symptoms suggestive to benign prostatic hyperplasia on male sexual functions

    Directory of Open Access Journals (Sweden)

    Shih-Tsung Huang

    2016-03-01

    Full Text Available Although alpha blockers with or without 5-alpha reductase inhibitors (5-ARIs have become the standard of treatment for men with moderate to severe lower urinary tract symptoms suggestive to benign prostatic hyperplasia (LUTS/BPH, their negative adverse effects on male sexual functions have become another major issue, which may have a direct impact on patients' quality of life and overall satisfaction. Erectile dysfunction, ejaculation disorders, reduced libido, or anorgasmia have been noted among patients receiving these standards of treatments and these adverse events may be irreversible even after discontinuation of medications. Physicians should inform and discuss with their patients about these potential side effects before prescribing these medications for their LUTS/BPH treatment. Tadalafil is the first phosphodiesterase type 5 inhibitor which has the indications for LUTS/BPH and erectile dysfunction and its efficacy is comparable to alpha-blockers with regards to the reduction of LUTS and improvement of quality of life. Moreover, early clinical studies have showed that the combination use tadalafil with alpha blockers or 5-ARIs may have an additional benefit on symptom relief and maximum urinary flow rate (Qmax improvement. As expected, the improvement on erectile function is significant, especially among patients taking 5-ARIs regularly. Although there are promising data from the combination use of tadalafil with 5-ARIs or tadalafil with alpha-blockers, more large-scale clinical studies are still needed to confirm their long term safety and efficacy profiles.

  19. Validation of the fatigue scale for motor and cognitive functions in a danish multiple sclerosis cohort

    DEFF Research Database (Denmark)

    Oervik, M. S.; Sejbaek, T.; Penner, I. K.

    2017-01-01

    Background Our objective was to validate the Danish translation of the Fatigue Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS) patients. Materials and methods A Danish MS cohort (n = 84) was matched and compared to the original German validation cohort (n = 309) and a he......Background Our objective was to validate the Danish translation of the Fatigue Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS) patients. Materials and methods A Danish MS cohort (n = 84) was matched and compared to the original German validation cohort (n = 309...... positive correlations between the two fatigue scales implied high convergent validity (total scores: r = 0.851, p gender). Correcting for depression did not result in any significant adjustments of the correlations...

  20. Adaptive modified function projective synchronization of multiple time-delayed chaotic Rossler system

    International Nuclear Information System (INIS)

    Sudheer, K. Sebastian; Sabir, M.

    2011-01-01

    In this Letter we consider modified function projective synchronization of unidirectionally coupled multiple time-delayed Rossler chaotic systems using adaptive controls. Recently, delay differential equations have attracted much attention in the field of nonlinear dynamics. The high complexity of the multiple time-delayed systems can provide a new architecture for enhancing message security in chaos based encryption systems. Adaptive control can be used for synchronization when the parameters of the system are unknown. Based on Lyapunov stability theory, the adaptive control law and the parameter update law are derived to make the state of two chaotic systems are function projective synchronized. Numerical simulations are presented to demonstrate the effectiveness of the proposed adaptive controllers.

  1. Jigsaw puzzle metasurface for multiple functions: polarization conversion, anomalous reflection and diffusion.

    Science.gov (United States)

    Zhao, Yi; Cao, Xiangyu; Gao, Jun; Liu, Xiao; Li, Sijia

    2016-05-16

    We demonstrate a simple reconfigurable metasurface with multiple functions. Anisotropic tiles are investigated and manufactured as fundamental elements. Then, the tiles are combined in a certain sequence to construct a metasurface. Each of the tiles can be adjusted independently which is like a jigsaw puzzle and the whole metasurface can achieve diverse functions by different layouts. For demonstration purposes, we realize polarization conversion, anomalous reflection and diffusion by a jigsaw puzzle metasurface with 6 × 6 pieces of anisotropic tile. Simulated and measured results prove that our method offers a simple and effective strategy for metasurface design.

  2. Use of multiple functional traits of protozoa for bioassessment of marine pollution.

    Science.gov (United States)

    Zhong, Xiaoxiao; Xu, Guangjian; Xu, Henglong

    2017-06-30

    Ecological parameters based on multiply functional traits have many advantages for monitoring programs by reducing "signal to noise" ratios of observed species data. To identify potential indicators for bioassessment of marine pollution in function space, the functional patterns of protozoan communities and relationships with environmental changes were studied in coastal waters of the Yellow Sea during a 1-year period. The results showed that: (1) the spatial variability in functional trait distributions of the protozoa was significantly associated with changes in environmental variables, especially chemical oxygen demand (COD) and nutrients on spatial scale; (2) the functional traits, especially food resources and feeding type, were significantly correlated with COD and nutrients; and (3) the functional diversity indices were generally related to nutrients or COD. Based on the results, we suggest that the functional traits and diversity indices of protozoan communities may be used as more effective indicators for bioassessment of marine pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Charged Particles Multiplicity and Scaling Violation of Fragmentation Functions in Electron-Positron Annihilation

    International Nuclear Information System (INIS)

    Ghaffary, Tooraj

    2016-01-01

    By the use of data from the annihilation process of electron-positron in AMY detector at 60 GeV center of mass energy, charged particles multiplicity distribution is obtained and fitted with the KNO scaling. Then, momentum spectra of charged particles and momentum distribution with respect to the jet axis are obtained, and the results are compared to the different models of QCD; also, the distribution of fragmentation functions and scaling violations are studied. It is being expected that the scaling violations of the fragmentation functions of gluon jets are stronger than the quark ones. One of the reasons for such case is that splitting function of quarks is larger than splitting function of gluon.

  4. Functional and structural balances of homologous sensorimotor regions in multiple sclerosis fatigue

    DEFF Research Database (Denmark)

    Cogliati Dezza, I; Zito, G; Tomasevic, L

    2015-01-01

    regions-known to be crucial for sensorimotor networks effectiveness-decrease with MS fatigue increase. Functional connectivity measures at rest and during a simple motor task (weak handgrip of either the right or left hand) were derived from primary sensorimotor areas electroencephalographic recordings......Fatigue in multiple sclerosis (MS) is a highly disabling symptom. Among the central mechanisms behind it, an involvement of sensorimotor networks is clearly evident from structural and functional studies. We aimed at assessing whether functional/structural balances of homologous sensorimotor...... in 27 mildly disabled MS patients. Structural MRI-derived inter-hemispheric asymmetries included the cortical thickness of Rolandic regions and the volume of thalami. Fatigue symptoms increased together with the functional inter-hemispheric imbalance of sensorimotor homologous areas activities at rest...

  5. A multiplicative process for generating a beta-like survival function with application to the UK 2016 EU referendum results

    Science.gov (United States)

    Fenner, Trevor; Kaufmann, Eric; Levene, Mark; Loizou, George

    Human dynamics and sociophysics suggest statistical models that may explain and provide us with better insight into social phenomena. Contextual and selection effects tend to produce extreme values in the tails of rank-ordered distributions of both census data and district-level election outcomes. Models that account for this nonlinearity generally outperform linear models. Fitting nonlinear functions based on rank-ordering census and election data therefore improves the fit of aggregate voting models. This may help improve ecological inference, as well as election forecasting in majoritarian systems. We propose a generative multiplicative decrease model that gives rise to a rank-order distribution and facilitates the analysis of the recent UK EU referendum results. We supply empirical evidence that the beta-like survival function, which can be generated directly from our model, is a close fit to the referendum results, and also may have predictive value when covariate data are available.

  6. Differential co-localization with choline acetyltransferase in nervus terminalis suggests functional differences for GnRH isoforms in bonnethead sharks (Sphyrna tiburo).

    Science.gov (United States)

    Moeller, John F; Meredith, Michael

    2010-12-17

    The nervus terminalis (NT) is a vertebrate cranial nerve whose function in adults is unknown. In bonnethead sharks, the nerve is anatomically independent of the olfactory system, with two major cell populations within one or more ganglia along its exposed length. Most cells are immunoreactive for either gonadotropin-releasing hormone (GnRH) or RF-amide-like peptides. To define further the cell populations and connectivity, we used double-label immunocytochemistry with antisera to different isoforms of GnRH and to choline acetyltransferase (ChAT). The labeling patterns of two GnRH antisera revealed different populations of GnRH-immunoreactive (ir) cell profiles in the NT ganglion. One antiserum labeled a large group of cells and fibers, which likely contain mammalian GnRH (GnRH-I) as described in previous studies and which were ChAT immunoreactive. The other antiserum labeled large club-like structures, which were anuclear, and a sparse number of fibers, but with no clear labeling of cell bodies in the ganglion. These club structures were choline acetyltrasferase (ChAT)-negative, and preabsorption control tests suggest they may contain chicken-GnRH-II (GnRH-II) or dogfish GnRH. The second major NT ganglion cell-type was immunoreactive for RF-amides, which regulate GnRH release in other vertebrates, and may provide an intraganglionic influence on GnRH release. The immunocytochemical and anatomical differences between the two GnRH-immunoreactive profile types indicate possible functional differences for these isoforms in the NT. The club-like structures may be sites of GnRH release into the general circulation since these structures were observed near blood vessels and resembled structures seen in the median eminence of rats. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Gene expression and immunohistochemical analyses of mKast suggest its late pupal and adult-specific functions in the honeybee brain.

    Directory of Open Access Journals (Sweden)

    Atsuhiro Yamane

    Full Text Available In insect brains, the mushroom bodies (MBs, a higher center comprise intrinsic neurons, termed Kenyon cells (KCs. We previously showed that the honeybee (Apis mellifera L. MBs comprise four types of KCs, in addition to the previously known three types of KCs: class I large-type KCs (lKCs, class I small-type KCs (sKCs and class II KCs, novel class I 'middle-type' KCs (mKCs, which are characterized by the preferential expression of a gene, termed mKast. Although mKast was originally discovered during the search for genes whose expression is enriched in the optic lobes (OLs in the worker brain, subsequent analysis revealed that the gene is expressed in an mKC-preferential manner in the MBs. To gain more insights into the function of mKast in the honeybee brain, we here performed expression analysis of mKast and immunohistochemistry of the mKast protein. Prominent mKast expression was first detected in the brain after the P7 pupal stage. In addition, mKast was expressed almost selectively in the brain, suggesting its late pupal and adult specific functions in the brain. Immunohistochemistry revealed that mKast-like immunoreactivity is detected in several regions in the worker brain: inside and around the MB calyces, at the outer edges of the OL lobula, at the outer surface of and posterior to the antennal lobes (ALs, along the dorsal midline of the anterior brain and at the outer surface of the subesophageal ganglions (SOG. mKast-like immunoreactivities in the MBs, OLs, ALs and SOG were due to the corresponding neurons, while mKast-like immunoreactivities beneath/between the MB calyces were assumed to most likely correspond to the lateral/medial neurosecretory cells.

  8. Amino acid composition of the bushcricket spermatophore and the function of courtship feeding: Variable composition suggests a dynamic role of the nuptial gift.

    Science.gov (United States)

    Jarrige, Alicia; Body, Mélanie; Giron, David; Greenfield, Michael D; Goubault, Marlène

    2015-11-01

    Nuptial gifts are packages of non-gametic material transferred by males to females at mating. These gifts are common in bushcrickets, where males produce a complex spermatophore consisting in a sperm-containing ampulla and an edible sperm-free spermatophylax. Two non-mutually exclusive hypotheses have been suggested to explain the function of the spermatophylax: the paternal investment hypothesis proposes that it represents a male nutritional investment in offspring; the mating effort hypothesis proposes that the spermatophylax maximizes the male's sperm transfer. Because gift production may represent significant energy expenditure, males are expected to adjust their investment relative to the perceived quality of the female. In this study, we first examined the free amino acid composition and protein-bound amino acid composition of the nuptial gift in the bushcricket, Ephippiger diurnus (Orthoptera: Tettigoniidae). Second, we investigated whether this composition was altered according to female age and body weight. Our study represents the first investigation of both free and protein-bound amino acid fractions of a bushcricket spermatophylax. We found that composition of the nuptial gift varied both qualitatively and quantitatively with respect to traits of the receiving female: older females received larger amounts of protein-bound amino acids (both essential and non-essential), less water and less free glycine. This result suggests that gift composition is highly labile in E. diurnus, and we propose that gift allocation might represent a form of cryptic male mate choice, allowing males to maximize their chances of paternity according to the risk of sperm competition that is associated with mate quality. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Multiple populations within globular clusters in Early-type galaxies Exploring their effect on stellar initial mass function estimates

    Science.gov (United States)

    Chantereau, W.; Usher, C.; Bastian, N.

    2018-05-01

    It is now well-established that most (if not all) ancient globular clusters host multiple populations, that are characterised by distinct chemical features such as helium abundance variations along with N-C and Na-O anti-correlations, at fixed [Fe/H]. These very distinct chemical features are similar to what is found in the centres of the massive early-type galaxies and may influence measurements of the global properties of the galaxies. Additionally, recent results have suggested that M/L variations found in the centres of massive early-type galaxies might be due to a bottom-heavy stellar initial mass function. We present an analysis of the effects of globular cluster-like multiple populations on the integrated properties of early-type galaxies. In particular, we focus on spectral features in the integrated optical spectrum and the global mass-to-light ratio that have been used to infer variations in the stellar initial mass function. To achieve this we develop appropriate stellar population synthesis models and take into account, for the first time, an initial-final mass relation which takes into consideration a varying He abundance. We conclude that while the multiple populations may be present in massive early-type galaxies, they are likely not responsible for the observed variations in the mass-to-light ratio and IMF sensitive line strengths. Finally, we estimate the fraction of stars with multiple populations chemistry that come from disrupted globular clusters within massive ellipticals and find that they may explain some of the observed chemical patterns in the centres of these galaxies.

  10. Resource partitioning along multiple niche axes drives functional diversity in parrotfishes on Caribbean coral reefs.

    Science.gov (United States)

    Adam, Thomas C; Kelley, Megan; Ruttenberg, Benjamin I; Burkepile, Deron E

    2015-12-01

    The recent loss of key consumers to exploitation and habitat degradation has significantly altered community dynamics and ecosystem function across many ecosystems worldwide. Predicting the impacts of consumer losses requires knowing the level of functional diversity that exists within a consumer assemblage. In this study, we document functional diversity among nine species of parrotfishes on Caribbean coral reefs. Parrotfishes are key herbivores that facilitate the maintenance and recovery of coral-dominated reefs by controlling algae and provisioning space for the recruitment of corals. We observed large functional differences among two genera of parrotfishes that were driven by differences in diet. Fishes in the genus Scarus targeted filamentous algal turf assemblages, crustose coralline algae, and endolithic algae and avoided macroalgae, while fishes in the genus Sparisoma preferentially targeted macroalgae. However, species with similar diets were dissimilar in other attributes, including the habitats they frequented, the types of substrate they fed from, and the spatial scale at which they foraged. These differences indicate that species that appear to be functionally redundant when looking at diet alone exhibit high levels of complementarity when we consider multiple functional traits. By identifying key functional differences among parrotfishes, we provide critical information needed to manage parrotfishes to enhance the resilience of coral-dominated reefs and reverse phase shifts on algal-dominated reefs throughout the wider Caribbean. Further, our study provides a framework for predicting the impacts of consumer losses in other species rich ecosystems.

  11. Balance functions: Multiplicity and transverse momentum dependence of the charge dependent correlations in ALICE

    CERN Document Server

    AUTHOR|(CDS)2078856; Snellings, Raimond; Christakoglou, Panos

    The measurement of charge-dependent correlations between positively and negatively charged particles as a function of pseudorapidity and azimuthal angle, known as the balance functions, provide insight to the properties of matter created in high-energy collisions. The balance functions are argued to probe the creation time of the particles and are also sensitive to the collective motion of the system. In this thesis, I present the results of the measured balance functions in p--Pb collisions at √sNN = 5.02~TeV obtained with the ALICE detector at the LHC. The results are compared with balance functions measured in pp and Pb--Pb collisions at √s=7~TeV and √sNN = 2.76~TeV$, respectively. The width of the balance functions in both pseudorapidity and azimuthal angle for non-identified charged particles decreases with increasing multiplicity in all three systems, for particles with low transverse momentum value pT < 2~GeV/c. For higher values of transverse momentum the balance functions become narrower and...

  12. The function of communities in protein interaction networks at multiple scales

    Directory of Open Access Journals (Sweden)

    Jones Nick S

    2010-07-01

    Full Text Available Abstract Background If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. Results Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein. Conclusions We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.

  13. Eight novel F13A1 gene missense mutations in patients with mild FXIII deficiency: in silico analysis suggests changes in FXIII-A subunit structure/function.

    Science.gov (United States)

    Biswas, Arijit; Ivaskevicius, Vytautas; Thomas, Anne; Varvenne, Michael; Brand, Brigitte; Rott, Hannelore; Haussels, Iris; Ruehl, Heiko; Scholz, Ute; Klamroth, Robert; Oldenburg, Johannes

    2014-10-01

    Mild FXIII deficiency is an under-diagnosed disorder because the carriers of this deficiency are often asymptomatic and reveal a phenotype only under special circumstances like surgery or induced trauma. Mutational reports from this type of deficiency have been rare. In this study, we present the phenotypic and genotypic data of nine patients showing mild FXIII-A deficiency caused by eight novel heterozygous missense mutations (Pro166Leu, Arg171Gln, His342Tyr, Gln415Arg, Leu529Pro, Gln601Lys, Arg703Gln and Arg715Gly) in the F13A1 gene. None of these variants were seen in 200 healthy controls. In silico structural analysis of the local wild-type protein structures (activated and non-activated) from X-ray crystallographic models downloaded from the protein databank identified potential structural/functional effects for the identified mutations. The missense mutations in the core domain are suggested to be directly influencing the catalytic triad. Mutations on other domains might influence other critical factors such as activation peptide cleavage or the barrel domain integrity. In vitro expression and subsequent biochemical studies in the future will be able to confirm the pathophysiological mechanisms proposed for the mutations in this article.

  14. Synthesis of Carbon Dots with Multiple Color Emission by Controlled Graphitization and Surface Functionalization.

    Science.gov (United States)

    Miao, Xiang; Qu, Dan; Yang, Dongxue; Nie, Bing; Zhao, Yikang; Fan, Hongyou; Sun, Zaicheng

    2018-01-01

    Multiple-color-emissive carbon dots (CDots) have potential applications in various fields such as bioimaging, light-emitting devices, and photocatalysis. The majority of the current CDots to date exhibit excitation-wavelength-dependent emissions with their maximum emission limited at the blue-light region. Here, a synthesis of multiple-color-emission CDots by controlled graphitization and surface function is reported. The CDots are synthesized through controlled thermal pyrolysis of citric acid and urea. By regulating the thermal-pyrolysis temperature and ratio of reactants, the maximum emission of the resulting CDots gradually shifts from blue to red light, covering the entire light spectrum. Specifically, the emission position of the CDots can be tuned from 430 to 630 nm through controlling the extent of graphitization and the amount of surface functional groups, COOH. The relative photoluminescence quantum yields of the CDots with blue, green, and red emission reach up to 52.6%, 35.1%, and 12.9%, respectively. Furthermore, it is demonstrated that the CDots can be uniformly dispersed into epoxy resins and be fabricated as transparent CDots/epoxy composites for multiple-color- and white-light-emitting devices. This research opens a door for developing low-cost CDots as alternative phosphors for light-emitting devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple Pollutants with High Performance.

    Science.gov (United States)

    Pan, Shunlong; Li, Jiansheng; Noonan, Owen; Fang, Xiaofeng; Wan, Gaojie; Yu, Chengzhong; Wang, Lianjun

    2017-05-02

    Simultaneous removal of multiple pollutants from aqueous solution with less energy consumption is crucial in water purification. Here, a novel concept of dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of nanostructured adsorbents into the finger-like pores of ultrafiltration (UF) membrane rather than in the membrane matrix in previous reports of blend membranes, resulting in an exceptionally high active content and simultaneous removal of multiple pollutants from water due to the dual functions of rejection and adsorption. As a demonstration, hollow porous Zr(OH) x nanospheres (HPZNs) were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine coating with a high content of 68.9 wt %. The decontamination capacity of DFUF membranes toward multiple model pollutants (colloidal gold, polyethylene glycol (PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10 ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively removed the colloidal gold and PEG below instrument detection limit, however the blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of nanoadsorbents during testing; and the membrane can be easily regenerated and reused. This study sheds new light on the design of high performance multifunction membranes for drinking water purification.

  16. Multiple logic functions from extended blockade region in a silicon quantum-dot transistor

    International Nuclear Information System (INIS)

    Lee, Youngmin; Lee, Sejoon; Im, Hyunsik; Hiramoto, Toshiro

    2015-01-01

    We demonstrate multiple logic-functions at room temperature on a unit device of the Si single electron transistor (SET). Owing to the formation of the multi-dot system, the device exhibits the enhanced Coulomb blockade characteristics (e.g., large peak-to-valley current ratio ∼200) that can improve the reliability of the SET-based logic circuits. The SET displays a unique feature useful for the logic applications; namely, the Coulomb oscillation peaks are systematically shifted by changing either of only the gate or the drain voltage. This enables the SET to act as a multi-functional one-transistor logic gate with AND, OR, NAND, and XOR functions

  17. Multiple logic functions from extended blockade region in a silicon quantum-dot transistor

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Youngmin; Lee, Sejoon, E-mail: sejoon@dongguk.edu; Im, Hyunsik [Department of Semiconductor Science, Dongguk University-Seoul, Seoul 100-715 (Korea, Republic of); Hiramoto, Toshiro [Institute of Industrial Science, University of Tokyo, Tokyo 153-8505 (Japan)

    2015-02-14

    We demonstrate multiple logic-functions at room temperature on a unit device of the Si single electron transistor (SET). Owing to the formation of the multi-dot system, the device exhibits the enhanced Coulomb blockade characteristics (e.g., large peak-to-valley current ratio ∼200) that can improve the reliability of the SET-based logic circuits. The SET displays a unique feature useful for the logic applications; namely, the Coulomb oscillation peaks are systematically shifted by changing either of only the gate or the drain voltage. This enables the SET to act as a multi-functional one-transistor logic gate with AND, OR, NAND, and XOR functions.

  18. Multiple-scanning-probe tunneling microscope with nanoscale positional recognition function.

    Science.gov (United States)

    Higuchi, Seiji; Kuramochi, Hiromi; Laurent, Olivier; Komatsubara, Takashi; Machida, Shinichi; Aono, Masakazu; Obori, Kenichi; Nakayama, Tomonobu

    2010-07-01

    Over the past decade, multiple-scanning-probe microscope systems with independently controlled probes have been developed for nanoscale electrical measurements. We developed a quadruple-scanning-probe tunneling microscope (QSPTM) that can determine and control the probe position through scanning-probe imaging. The difficulty of operating multiple probes with submicrometer precision drastically increases with the number of probes. To solve problems such as determining the relative positions of the probes and avoiding of contact between the probes, we adopted sample-scanning methods to obtain four images simultaneously and developed an original control system for QSPTM operation with a function of automatic positional recognition. These improvements make the QSPTM a more practical and useful instrument since four images can now be reliably produced, and consequently the positioning of the four probes becomes easier owing to the reduced chance of accidental contact between the probes.

  19. Experimental design and multiple response optimization. Using the desirability function in analytical methods development.

    Science.gov (United States)

    Candioti, Luciana Vera; De Zan, María M; Cámara, María S; Goicoechea, Héctor C

    2014-06-01

    A review about the application of response surface methodology (RSM) when several responses have to be simultaneously optimized in the field of analytical methods development is presented. Several critical issues like response transformation, multiple response optimization and modeling with least squares and artificial neural networks are discussed. Most recent analytical applications are presented in the context of analytLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, ArgentinaLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, Argentinaical methods development, especially in multiple response optimization procedures using the desirability function. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Multiple exciton generation in chiral carbon nanotubes: Density functional theory based computation

    Science.gov (United States)

    Kryjevski, Andrei; Mihaylov, Deyan; Kilina, Svetlana; Kilin, Dmitri

    2017-10-01

    We use a Boltzmann transport equation (BE) to study time evolution of a photo-excited state in a nanoparticle including phonon-mediated exciton relaxation and the multiple exciton generation (MEG) processes, such as exciton-to-biexciton multiplication and biexciton-to-exciton recombination. BE collision integrals are computed using Kadanoff-Baym-Keldysh many-body perturbation theory based on density functional theory simulations, including exciton effects. We compute internal quantum efficiency (QE), which is the number of excitons generated from an absorbed photon in the course of the relaxation. We apply this approach to chiral single-wall carbon nanotubes (SWCNTs), such as (6,2) and (6,5). We predict efficient MEG in the (6,2) and (6,5) SWCNTs within the solar spectrum range starting at the 2Eg energy threshold and with QE reaching ˜1.6 at about 3Eg, where Eg is the electronic gap.

  1. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue.

    Science.gov (United States)

    Rosalie Driehuis, Emma; van den Akker, Lizanne Eva; de Groot, Vincent; Beckerman, Heleen

    2018-02-13

    To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. A cross-sectional study. Sixty-two participants with multiple sclerosis-related fatigue. Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min). Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), physical functioning with the Short Form 36 - physical functioning (SF36-pf), and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA). Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status). Mean maximal oxygen uptake (VO2max) was 23.9 ml/kg/min (standard deviation (SD) 6.3 ml/kg/min). There was no significant relationship between VO2max and physical activity (PASIPD): β = 0.320, 95% confidence interval (95% CI) = -0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf): β = 1.527, 95% CI = 0.820-2.234, R2 = 25.9%, and was significantly related to IPA domains "autonomy indoors" (β = -0.043, 95% CI = -0.067 to -0.020, R2 = 20.6%), "autonomy outdoors" (β = -0.037, 95% CI = -0.062 to -0.012, R2 = 18.2%) and "social life and relationships" (β=-0.033, 95% CI = -0.060 to -0.007, R2 = 21.3%). Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

  2. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue

    Directory of Open Access Journals (Sweden)

    Emma Rosalie Driehuis

    2018-01-01

    Full Text Available Objective: To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. Design: A cross-sectional study. Patients: Sixty-two participants with multiple sclerosis-related fatigue. Methods: Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min. Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD, physical functioning with the Short Form 36 – physical functioning (SF36-pf, and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA. Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status. Results: Mean maximal oxygen uptake (VO2max was 23.9 ml/kg/min (standard deviation (SD 6.3 ml/kg/min. There was no significant relationship between VO2max and physical activity (PASIPD: β = 0.320, 95% confidence interval (95% CI = –0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf: β = 1.527, 95% CI = 0.820–2.234, R2 = 25.9%, and was significantly related to IPA domains “autonomy indoors” (β = –0.043, 95% CI = –0.067 to –0.020, R2 = 20.6%, “autonomy outdoors” (β = –0.037, 95% CI = –0.062 to –0.012, R2 = 18.2% and “social life and relationships” (β=–0.033, 95% CI = –0.060 to –0.007, R2 = 21.3%. Conclusion: Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

  3. Comparative evaluation of Plateletworks, Multiplate analyzer and Platelet function analyzer-200 in cardiology patients.

    Science.gov (United States)

    Kim, Jeeyong; Cho, Chi Hyun; Jung, Bo Kyeung; Nam, Jeonghun; Seo, Hong Seog; Shin, Sehyun; Lim, Chae Seung

    2018-04-14

    The objective of this study was to comparatively evaluate three commercial whole-blood platelet function analyzer systems: Platelet Function Analyzer-200 (PFA; Siemens Canada, Mississauga, Ontario, Canada), Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and Plateletworks Combo-25 kit (PLW; Helena Laboratories, Beaumont, TX, USA). Venipuncture was performed on 160 patients who visited a department of cardiology. Pairwise agreement among the three platelet function assays was assessed using Cohen's kappa coefficient and percent agreement within the reference limit. Kappa values with the same agonists were poor between PFA-collagen (COL; agonist)/adenosine diphosphate (ADP) and MP-ADP (-0.147), PFA-COL/ADP and PLW-ADP (0.089), MP-ADP and PLW-ADP (0.039), PFA-COL/ADP and MP-COL (-0.039), and between PFA-COL/ADP and PLW-COL (-0.067). Nonetheless, kappa values for the same assay principle with a different agonist were slightly higher between PFA-COL/ADP and PFA-COL/EPI (0.352), MP-ADP and MP-COL (0.235), and between PLW-ADP and PLW-COL (0.247). The range of percent agreement values was 38.7% to 73.8%. Therefore, various measurements of platelet function by more than one method were needed to obtain a reliable interpretation of platelet function considering low kappa coefficient and modest percent agreement rates among 3 different platelet function tests.

  4. The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

    Science.gov (United States)

    Golan, Daniel; Doniger, Glen M; Wissemann, Karl; Zarif, Myassar; Bumstead, Barbara; Buhse, Marijean; Fafard, Lori; Lavi, Idit; Wilken, Jeffrey; Gudesblatt, Mark

    2018-02-01

    The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

  5. Regional resources buffer the impact of functional limitations on perceived autonomy in older adults with multiple illnesses.

    Science.gov (United States)

    Schüz, Benjamin; Westland, Josh N; Wurm, Susanne; Tesch-Römer, Clemens; Wolff, Julia K; Warner, Lisa M; Schwarzer, Ralf

    2016-03-01

    Retaining perceptions of autonomy is a key component of successful aging. Perceived autonomy refers to the capacity to make and enact self-directed decisions. These perceptions are often threatened in older adults with multiple illnesses, when functional limitations resulting from these illnesses impede the enactment of self-directed decisions. Regional resources (in Germany specifically at the level of administrative districts) might counteract these impediments of autonomy. Economically stronger districts can provide more-concrete support resources for older adults, buffering the negative effect of functional limitations on self-perceived autonomy. This study assessed participants aged over 65 with 2 or more chronic conditions. In total, N = 287 provided data (Mage = 73.3, SD = 5.07), and n = 97 were women. Gross domestic product (GDP) per capita was used as a proxy measure of administrative district wealth in Germany. Hierarchical multilevel regression analyses with cross-level interactions were conducted. Results suggest that the detrimental effect of functional limitations on perceived autonomy is less pronounced for participants residing in higher GDP districts. Conversely, for participants in lower GDP districts, the effect is exacerbated. This finding suggests that districts with greater financial resources might be better able to invest in supports that promote and facilitate autonomy and, thus, provide a buffer against threats to individual perceived autonomy. (c) 2016 APA, all rights reserved).

  6. Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

    2018-02-01

    Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Proteomics analysis suggests broad functional changes in potato leaves triggered by phosphites and a complex indirect mode of action against Phytophthora infestans.

    Science.gov (United States)

    Lim, Sanghyun; Borza, Tudor; Peters, Rick D; Coffin, Robert H; Al-Mughrabi, Khalil I; Pinto, Devanand M; Wang-Pruski, Gefu

    2013-11-20

    Phosphite (salts of phosphorous acid; Phi)-based fungicides are increasingly used in controlling oomycete pathogens, such as the late blight agent Phytophthora infestans. In plants, low amounts of Phi induce pathogen resistance through an indirect mode of action. We used iTRAQ-based quantitative proteomics to investigate the effects of phosphite on potato plants before and after infection with P. infestans. Ninety-three (62 up-regulated and 31 down-regulated) differentially regulated proteins, from a total of 1172 reproducibly identified proteins, were identified in the leaf proteome of Phi-treated potato plants. Four days post-inoculation with P. infestans, 16 of the 31 down-regulated proteins remained down-regulated and 42 of the 62 up-regulated proteins remained up-regulated, including 90% of the defense proteins. This group includes pathogenesis-related, stress-responsive, and detoxification-related proteins. Callose deposition and ultrastructural analyses of leaf tissues after infection were used to complement the proteomics approach. This study represents the first comprehensive proteomics analysis of the indirect mode of action of Phi, demonstrating broad effects on plant defense and plant metabolism. The proteomics data and the microscopy study suggest that Phi triggers a hypersensitive response that is responsible for induced resistance of potato leaves against P. infestans. Phosphie triggers complex functional changes in potato leaves that are responsible for the induced resistance against Phytophthora infestans. This article is part of a Special Issue entitled: Translational Plant Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Edaphic, structural and physiological contrasts across Amazon Basin forest–savanna ecotones suggest a role for potassium as a key modulator of tropical woody vegetation structure and function

    Directory of Open Access Journals (Sweden)

    J. Lloyd

    2015-11-01

    C / N ratios than nearby forest plots. These soil differences were also reflected in canopy averaged leaf traits with savanna trees typically having higher leaf mass per unit area but lower mass-based nitrogen (Nm and potassium (Km. Both Nm and Km also increased with declining mean annual precipitation (PA, but most area-based leaf traits such as leaf photosynthetic capacity showed no systematic variation with PA or vegetation type. Despite this invariance, when taken in conjunction with other measures such as mean canopy height, area-based soil exchangeable potassium content, [K]sa , proved to be an excellent predictor of several photosynthetic properties (including 13C isotope discrimination. Moreover, when considered in a multivariate context with PA and soil plant available water storage capacity (θP as covariates, [K]sa also proved to be an excellent predictor of stand-level canopy area, providing drastically improved fits as compared to models considering just PA and/or θP. Neither calcium, nor magnesium, nor soil pH could substitute for potassium when tested as alternative model predictors (ΔAIC > 10. Nor for any model could simple soil texture metrics such as sand or clay content substitute for either [K]sa or θP. Taken in conjunction with recent work in Africa and the forests of the Amazon Basin, this suggests – in combination with some newly conceptualised interacting effects of PA and θP also presented here – a critical role for potassium as a modulator of tropical vegetation structure and function.

  9. Functional microarray analysis suggests repressed cell-cell signaling and cell survival-related modules inhibit progression of head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Soares Fernando A

    2011-04-01

    Full Text Available Abstract Background Cancer shows a great diversity in its clinical behavior which cannot be easily predicted using the currently available clinical or pathological markers. The identification of pathways associated with lymph node metastasis (N+ and recurrent head and neck squamous cell carcinoma (HNSCC may increase our understanding of the complex biology of this disease. Methods Tumor samples were obtained from untreated HNSCC patients undergoing surgery. Patients were classified according to pathologic lymph node status (positive or negative or tumor recurrence (recurrent or non-recurrent tumor after treatment (surgery with neck dissection followed by radiotherapy. Using microarray gene expression, we screened tumor samples according to modules comprised by genes in the same pathway or functional category. Results The most frequent alterations were the repression of modules in negative lymph node (N0 and in non-recurrent tumors rather than induction of modules in N+ or in recurrent tumors. N0 tumors showed repression of modules that contain cell survival genes and in non-recurrent tumors cell-cell signaling and extracellular region modules were repressed. Conclusions The repression of modules that contain cell survival genes in N0 tumors reinforces the important role that apoptosis plays in the regulation of metastasis. In addition, because tumor samples used here were not microdissected, tumor gene expression data are represented together with the stroma, which may reveal signaling between the microenvironment and tumor cells. For instance, in non-recurrent tumors, extracellular region module was repressed, indicating that the stroma and tumor cells may have fewer interactions, which disable metastasis development. Finally, the genes highlighted in our analysis can be implicated in more than one pathway or characteristic, suggesting that therapeutic approaches to prevent tumor progression should target more than one gene or pathway

  10. Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

    Science.gov (United States)

    Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

    2013-11-01

    Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE

  11. Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading

    KAUST Repository

    Ellis, Joanne

    2017-09-14

    Sedimentation, nutrients and metal loading to coastal environments are increasing, associated with urbanization and global warming, hence there is a growing need to predict ecological responses to such change. Using a regression technique we predicted how maximum abundance of 20 macrobenthic taxa and 22 functional traits separately and interactively responded to these key stressors. The abundance of most taxa declined in response to sedimentation and metal loading while a unimodal response was often associated with nutrient loading. Optimum abundances for both taxa and traits occurred at relatively low stressor levels, highlighting the vulnerability of estuaries to increasing stressor loads. Individual taxa were more susceptible to stress than traits, suggesting that functional traits may be less sensitive for detecting changes in ecosystem health. Multiplicative effects were more common than additive interactions. The observed sensitivity of most taxa to increasing sedimentation and metal loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

  12. Cross Talk Analysis on Multiple Coupled Transmission Lines; (The calculation of transfer functions on multiple coupled tansmission lines in an inhomogeneous dielectric medium)

    DEFF Research Database (Denmark)

    Dalby, Arne Brejning

    1994-01-01

    A flow graph relating voltages and the forward and reflected propagation modes (¿ TEM) on multiple coupled transmission lines in an inhomogeneous dielectric medium is presented. This flow graph directy gives the different transfer functions, including S-parameters, in matrix form needed to calcul......A flow graph relating voltages and the forward and reflected propagation modes (¿ TEM) on multiple coupled transmission lines in an inhomogeneous dielectric medium is presented. This flow graph directy gives the different transfer functions, including S-parameters, in matrix form needed...

  13. Sexual function in multiple sclerosis. A 5-year follow-up study

    DEFF Research Database (Denmark)

    Stenager, E; Stenager, E N; Jensen, K

    1996-01-01

    Sexual dysfunction is known to occur in multiple sclerosis (MS). The purpose of the study is to describe the change in sexual function and symptoms in a longitudinal study. Forty-nine patients (27 females, 22 males) with definite MS were interviewed and examined with 5 years interval. The number...... of patients with sexual dysfunction increased significantly (p = 0.009) and involved females and males equally. Males usually had 1 or two symptoms of sexual dysfunction, while females frequently had 2 or more symptoms. It is concluded that the risk of sexual dysfunction increases over time. Further studies...

  14. Vibrations analysis and bifurcations in the self-sustained electromechanical system with multiple functions

    International Nuclear Information System (INIS)

    Yamapi, R.; Moukam Kakmeni, F.M.; Aziz-Alaoui, M.A.

    2005-07-01

    We consider in this paper the dynamics of the self-sustained electromechanical system with multiple functions, consisting of an electrical Rayleigh-Duffing oscillator, magnetically coupled with linear mechanical oscillators. The averaging and the balance harmonic method are used to and the amplitudes of the oscillatory states respectively in the autonomous and non-autonomous cases, and analyze the condition in which the quenching of self-sustained oscillations appears. The effects of the number of linear mechanical oscillators on the behavior of the model are discussed. Various bifurcation structures, the stability chart and the variation of the Lyapunov exponent are obtained, using numerical simulations of the equations of motion. (author)

  15. Alignment engineering in liquid crystalline elastomers: Free-form microstructures with multiple functionalities

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Hao; Cerretti, Giacomo; Wiersma, Diederik S., E-mail: camilla.parmeggiani@lens.unifi.it, E-mail: wiersma@lens.unifi.it [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); Wasylczyk, Piotr [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); Faculty of Physics, Institute of Experimental Physics, University of Warsaw, ul. Hoza 69, Warszawa 00-681 (Poland); Martella, Daniele [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); Dipartimento di Chimica “Ugo Schiff,” University of Florence, via della Lastruccia 3-13, 50019 Sesto Fiorentino (Italy); Parmeggiani, Camilla, E-mail: camilla.parmeggiani@lens.unifi.it, E-mail: wiersma@lens.unifi.it [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); CNR-INO, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy)

    2015-03-16

    We report a method to fabricate polymer microstructures with local control over the molecular orientation. Alignment control is achieved on molecular level in a structure of arbitrary form that can be from 1 to 100 μm in size, by fixing the local boundary conditions with micro-grating patterns. The method makes use of two-photon polymerization (Direct Laser Writing) and is demonstrated specifically in liquid-crystalline elastomers. This concept allows for the realization of free-form polymeric structures with multiple functionalities which are not possible to realize with existing techniques and which can be locally controlled by light in the micrometer scale.

  16. Multiple kernel learning using single stage function approximation for binary classification problems

    Science.gov (United States)

    Shiju, S.; Sumitra, S.

    2017-12-01

    In this paper, the multiple kernel learning (MKL) is formulated as a supervised classification problem. We dealt with binary classification data and hence the data modelling problem involves the computation of two decision boundaries of which one related with that of kernel learning and the other with that of input data. In our approach, they are found with the aid of a single cost function by constructing a global reproducing kernel Hilbert space (RKHS) as the direct sum of the RKHSs corresponding to the decision boundaries of kernel learning and input data and searching that function from the global RKHS, which can be represented as the direct sum of the decision boundaries under consideration. In our experimental analysis, the proposed model had shown superior performance in comparison with that of existing two stage function approximation formulation of MKL, where the decision functions of kernel learning and input data are found separately using two different cost functions. This is due to the fact that single stage representation helps the knowledge transfer between the computation procedures for finding the decision boundaries of kernel learning and input data, which inturn boosts the generalisation capacity of the model.

  17. Multiple parton scattering in nuclei: heavy quark energy loss and modified fragmentation functions

    International Nuclear Information System (INIS)

    Zhang Benwei; Wang, Enke; Wang Xinnian

    2005-01-01

    Multiple scattering, induced radiative energy loss and modified fragmentation functions of a heavy quark in nuclear matter are studied within the framework of generalized factorization in perturbative QCD. Modified heavy quark fragmentation functions and energy loss are derived in detail with illustration of the mass dependencies of the Landau-Pomeranchuk-Migdal interference effects and heavy quark energy loss. Due to the quark mass dependence of the gluon formation time, the nuclear size dependencies of nuclear modification of the heavy quark fragmentation function and heavy quark energy loss are found to change from a linear to a quadratic form when the initial energy and momentum scale are increased relative to the quark mass. The radiative energy loss of the heavy quark is also significantly suppressed due to limited cone of gluon radiation imposed by the mass. Medium modification of the heavy quark fragmentation functions is found to be limited to the large z region due to the form of heavy quark fragmentation functions in vacuum

  18. Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Luca Prosperini

    2015-01-01

    Full Text Available Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS. In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI. In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations.

  19. Hypnosis, suggestion, and suggestibility: an integrative model.

    Science.gov (United States)

    Lynn, Steven Jay; Laurence, Jean-Roch; Kirsch, Irving

    2015-01-01

    This article elucidates an integrative model of hypnosis that integrates social, cultural, cognitive, and neurophysiological variables at play both in and out of hypnosis and considers their dynamic interaction as determinants of the multifaceted experience of hypnosis. The roles of these variables are examined in the induction and suggestion stages of hypnosis, including how they are related to the experience of involuntariness, one of the hallmarks of hypnosis. It is suggested that studies of the modification of hypnotic suggestibility; cognitive flexibility; response sets and expectancies; the default-mode network; and the search for the neurophysiological correlates of hypnosis, more broadly, in conjunction with research on social psychological variables, hold much promise to further understanding of hypnosis.

  20. Role of executive functions in prospective memory in multiple sclerosis: Impact of the strength of cue-action association.

    Science.gov (United States)

    Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

    2016-01-01

    Patients diagnosed with multiple sclerosis (MS) often report prospective memory (PM) deficits. Although PM is important for daily functioning, it is not formally assessed in clinical practice. The aim of this study was to examine the role of executive functions in MS patients' PM revealed by the effect of strength of cue-action association on PM performance. Thirty-nine MS patients were compared to 18 healthy controls matched for age, gender, and education on a PM task modulating the strength of association between the cue and the intended action. Deficits in MS patients affecting both prospective and retrospective components of PM were confirmed using 2 × 2 × 2 mixed analyses of variance (ANOVAs). Among patients, multiple regression analyses revealed that the impairment was modulated by the efficiency of executive functions, whereas retrospective memory seemed to have little impact on PM performance, contrary to expectation. More specifically, results of 2 × 2 × 2 mixed-model analyses of covariance (ANCOVAs) showed that low-executive patients had more difficulty detecting and, especially, retrieving the appropriate action when the cue and the action were unrelated, whereas high-executive patients' performance seemed to be virtually unaffected by the cue-action association. Using an objective measure, these findings confirm the presence of PM deficits in MS. They also suggest that such deficits depend on executive functioning and can be reduced when automatic PM processes are engaged through semantic cue-action association. They underscore the importance of assessing PM in clinical settings through a cognitive evaluation and offer an interesting avenue for rehabilitation.

  1. Analyzing the multiple functions of stereotypical behavior for students with autism: implications for assessment and treatment.

    Science.gov (United States)

    Kennedy, C H; Meyer, K A; Knowles, T; Shukla, S

    2000-01-01

    We studied behavioral functions associated with stereotypical responses for students with autism. In Study 1, analogue functional analyses (attention, demand, no-attention, and recreation conditions) were conducted for 5 students. Results suggested that stereotypy was multiply determined or occurred across all assessment conditions. For 2 students, stereotypy was associated with positive and negative reinforcement and the absence of environmental stimulation. For 2 other students, stereotypy occurred at high levels across all experimental conditions. For the 5th student, stereotypy was associated with negative reinforcement and the absence of environmental stimulation. In Study 2, the stereotypy of 1 student was further analyzed on a function-by-function basis. Within a concurrent-schedules procedure, alternative responses were taught to the student using functional communication training. The results of Study 2 showed that similar topographies of stereotypy, based on qualitatively different reinforcers, were reduced only when differential reinforcement contingencies for alternative forms of communication were implemented for specific response-reinforcer relations. Our results suggest that the causes of stereotypy for students with autism are complex and that the presumed association between response topography and behavioral function may be less important than previously realized.

  2. Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily.

    Science.gov (United States)

    Akiva, Eyal; Copp, Janine N; Tokuriki, Nobuhiko; Babbitt, Patricia C

    2017-11-07

    Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination of tools that include large-scale phylogenetic reconstruction to determine the sequence, structural, and functional relationships of the functionally diverse flavin mononucleotide-dependent nitroreductase (NTR) superfamily (>24,000 sequences from all domains of life, 54 structures, and >10 enzymatic functions). Our results suggest an evolutionary model in which contemporary subgroups of the superfamily have diverged in a radial manner from a minimal flavin-binding scaffold. We identified the structural design principle for this divergence: Insertions at key positions in the minimal scaffold that, combined with the fixation of key residues, have led to functional specialization. These results will aid future efforts to delineate the emergence of functional diversity in enzyme superfamilies, provide clues for functional inference for superfamily members of unknown function, and facilitate rational redesign of the NTR scaffold. Copyright © 2017 the Author(s). Published by PNAS.

  3. Measurement of hadron multiplicities in deep inelastic scattering and extraction of quark fragmentation functions

    International Nuclear Information System (INIS)

    Curiel-Garcia, Quiela-Marina

    2014-01-01

    One of the goals of the COMPASS experience is the study of the nucleon spin structure. Data were taken from a polarized muon beam (160 GeV/c) scattering off a polarized target ( 6 LiD or NH 3 ). In this context, the need of a precise knowledge of quark Fragmentation Functions (final-state hadronization of quarks q into hadrons h, FFs) was raised. The FFs can be extracted from hadron multiplicities produced in Semi-Inclusive Deep Inelastic Scattering (SIDIS). This thesis presents the measurement of charged hadrons (pions and kaons) multiplicities from SIDIS data collected in 2006. The data cover a large kinematical range: Q 2 ≥1 (GeV/c)2, y belongs to [0.1,0.9], x belongs to [0.004,0.7] and W belongs to [5,17] GeV. These multiplicities provide an important input for global QCD analyses of world data at NLO, aiming at the FFs determination. (author) [fr

  4. Unpolarised transverse momentum dependent distribution and fragmentation functions from SIDIS multiplicities

    International Nuclear Information System (INIS)

    Anselmino, M.; Boglione, M.; Gonzalez, H. J.O.; Melis, S.; Prokudin, A.

    2014-01-01

    In this study, the unpolarised transverse momentum dependent distribution and fragmentation functions are extracted from HERMES and COMPASS experimental measurements of SIDIS multiplicities for charged hadron production. The data are grouped into independent bins of the kinematical variables, in which the TMD factorisation is expected to hold. A simple factorised functional form of the TMDs is adopted, with a Gaussian dependence on the intrinsic transverse momentum, which turns out to be quite adequate in shape. HERMES data do not need any normalisation correction, while fits of the COMPASS data much improve with a y-dependent overall normalisation factor. A comparison of the extracted TMDs with previous EMC and JLab data confirms the adequacy of the simple gaussian distributions. The possible role of the TMD evolution is briefly considered

  5. Multiple nutritional deficiencies in cerebral palsy compounding physical and functional impairments

    Directory of Open Access Journals (Sweden)

    P G Hariprasad

    2017-01-01

    Full Text Available Introduction: Cerebral palsy (CP refers to a spectrum of disorders causing physical and intellectual morbidity. Macro and micro nutrient deficiencies often contribute to the subnormal physical and mental capabilities of them. Objectives: To assess the growth, nutritional status, physical and functional ability and quality of life in cerebral palsy children and to determine any relation with their gross motor and functional capabilities. Method: The study was conducted at a Tertiary Care Centre, with the participants in the age group 1-16 years. A pretested evaluation tool was prepared which included Anthropometric measurements, tests for hemoglobin and Vitamin D estimation, evidence of micronutrient deficiencies, Dietary patterns, Epidemiological factors, Functional assessment using GMFM (Gross Motor Function Measure and FIM (Functional Independent Measurement scales and Quality of life (QOL assessment. The data was statistically analyzed. Results: Out of the 41 children, 30 had quadriplegia, 3 had hemiplegia and 8 had spastic diplegia. 34 (82.9% were severely underweight, 35 (85.4% had severe stunting and 38 (92.7% had severe wasting. Micronutrient deficiencies were noted like vitamin B complex deficiency in 37 (90.2%, vitamin A deficiency in 31 (75.6%, low vitamin D levels in 27 (65.9% and insufficient levels in 9 (22%, severe anemia in 5 (12.2% and moderate anemia in 26 (63.4%.The gross motor and functional scores were suboptimum in the majority of patients and the care givers had significant impairment in the quality of life. Conclusion: Majority of children with cerebral palsy had multiple nutritional deficiencies, gross motor and functional disabilities. QOL of the children and their care givers were suboptimum. A comprehensive package that address dietary intake, correction of micronutrient deficiencies especially anemia and vitamin D deficiency, physical and emotional support is recommended for the wellbeing of the affected children.

  6. Finger and foot tapping as alternative outcomes of upper and lower extremity function in multiple sclerosis.

    Science.gov (United States)

    Tanigawa, Makoto; Stein, Jason; Park, John; Kosa, Peter; Cortese, Irene; Bielekova, Bibiana

    2017-01-01

    While magnetic resonance imaging contrast-enhancing lesions represent an excellent screening tool for disease-modifying treatments in relapsing-remitting multiple sclerosis (RRMS), this biomarker is insensitive for testing therapies against compartmentalized inflammation in progressive multiple sclerosis (MS). Therefore, alternative sensitive outcomes are needed. Using machine learning, clinician-acquired disability scales can be combined with timed measures of neurological functions such as walking speed (e.g. 25-foot walk; 25FW) or fine finger movements (e.g. 9-hole peg test; 9HPT) into sensitive composite clinical scales, such as the recently developed combinatorial, weight-adjusted disability scale (CombiWISE). Ideally, these complementary simplified measurements of certain neurological functions could be performed regularly at patients' homes using smartphones. We asked whether tests amenable to adaptation to smartphone technology, such as finger and foot tapping have comparable sensitivity and specificity to current non-clinician-acquired disability measures. We observed that finger and foot tapping can differentiate RRMS and progressive MS in a cross-sectional study and can also measure yearly and two-year disease progression in the latter, with better power (based on z-scores) in comparison to currently utilized 9HPT and 25FW. Replacing the 9HPT and 25FW with simplified tests broadly adaptable to smartphone technology may enhance the power of composite scales for progressive MS.

  7. Solution to PDEs using radial basis function finite-differences (RBF-FD) on multiple GPUs

    International Nuclear Information System (INIS)

    Bollig, Evan F.; Flyer, Natasha; Erlebacher, Gordon

    2012-01-01

    This paper presents parallelization strategies for the radial basis function-finite difference (RBF-FD) method. As a generalized finite differencing scheme, the RBF-FD method functions without the need for underlying meshes to structure nodes. It offers high-order accuracy approximation and scales as O(N) per time step, with N being with the total number of nodes. To our knowledge, this is the first implementation of the RBF-FD method to leverage GPU accelerators for the solution of PDEs. Additionally, this implementation is the first to span both multiple CPUs and multiple GPUs. OpenCL kernels target the GPUs and inter-processor communication and synchronization is managed by the Message Passing Interface (MPI). We verify our implementation of the RBF-FD method with two hyperbolic PDEs on the sphere, and demonstrate up to 9x speedup on a commodity GPU with unoptimized kernel implementations. On a high performance cluster, the method achieves up to 7x speedup for the maximum problem size of 27,556 nodes.

  8. The Effects of Massage Therapy on Multiple Sclerosis Patients’ Quality of Life and Leg Function

    Directory of Open Access Journals (Sweden)

    Brittany Schroeder

    2014-01-01

    Full Text Available Background. Massage therapy is a noninvasive treatment that many individuals with multiple sclerosis (MS use to supplement their conventional treatment. Objective. We hypothesize that massage therapy will improve the leg function and overall quality of life (QoL of MS patients. Design. A two-period (rest, massage crossover design was used. Twenty-four individuals with MS ranging from 3.0 to 7.0 on the Expanded Disability Status Scale (EDSS received Swedish massage treatments for four weeks. Exercise capacity and leg function as well as QoL were assessed using the Six-Minute Walk Test (6MWT and the Hamburg Quality of Life in Multiple Sclerosis (HAQUAMS instrument, respectively. Assessments were measured before and after a massage period and a rest period where no massages were employed. Results. The results displayed no significant changes in 6MWT distances or HAQUAMS scores. However, the participants perceived improvement in overall health as expressed in written comments. Conclusions. Massage is a safe, noninvasive treatment that may assist MS patients in managing the stress of their symptoms. Future studies with larger sample size and cortisol measures are warranted.

  9. Improving executive functioning in children with ADHD: training multiple executive functions within the context of a computer game. a randomized double-blind placebo controlled trial.

    Directory of Open Access Journals (Sweden)

    Sebastiaan Dovis

    Full Text Available Executive functions (EFs training interventions aimed at ADHD-symptom reduction have yielded mixed results. Generally, these interventions focus on training a single cognitive domain (e.g., working memory [WM], inhibition, or cognitive-flexibility. However, evidence suggests that most children with ADHD show deficits on multiple EFs, and that these EFs are largely related to different brain regions. Therefore, training multiple EFs might be a potentially more effective strategy to reduce EF-related ADHD symptoms.Eighty-nine children with a clinical diagnosis of ADHD (aged 8-12 were randomized to either a full-active-condition where visuospatial WM, inhibition and cognitive-flexibility were trained, a partially-active-condition where inhibition and cognitive-flexibility were trained and the WM-training task was presented in placebo-mode, or to a full placebo-condition. Short-term and long-term (3-months effects of this gamified, 25-session, home-based computer-training were evaluated on multiple outcome domains.During training compliance was high (only 3% failed to meet compliance criteria. After training, only children in the full-active condition showed improvement on measures of visuospatial short-term-memory (STM and WM. Inhibitory performance and interference control only improved in the full-active- and the partially-active condition. No Treatment-condition x Time interactions were found for cognitive-flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general problem behaviors. Nonetheless, almost all measures showed main Time-effects, including the teacher-ratings.Improvements on inhibition and visuospatial STM and WM were specifically related to the type of treatment received. However, transfer to untrained EFs and behaviors was mostly nonspecific (i.e., only interference control improved exclusively in the two EF training conditions. As such

  10. The assessment of problems in functioning and the subjective perception of these problems in people with Multiple Sclerosis : the Multiple Sclerosis Impact Profile (MSIP)

    NARCIS (Netherlands)

    Wynia, Klaske; Roodbol, Petrie F.; Middel, Berry

    People with Multiple Sclerosis (MS) perceive consequences of this chronic condition that are not limited to impairments in physical functioning but also have their impact on limitations in activities and restrictions in participation in life situations. There is a growing awareness among healthcare

  11. “The Relationship between Executive Functioning, Processing Speed and White Matter Integrity in Multiple Sclerosis”

    Science.gov (United States)

    Genova, Helen M.; DeLuca, John; Chiaravalloti, Nancy; Wylie, Glenn

    2014-01-01

    The primary purpose of the current study was to examine the relationship between performance on executive tasks and white matter integrity, assessed by diffusion tensor imaging (DTI) in Multiple Sclerosis (MS). A second aim was to examine how processing speed affects the relationship between executive functioning and FA. This relationship was examined in two executive tasks that rely heavily on processing speed: the Color-Word Interference Test and Trail-Making Test (Delis-Kaplan Executive Function System). It was hypothesized that reduced fractional anisotropy (FA) is related to poor performance on executive tasks in MS, but that this relationship would be affected by the statistical correction of processing speed from the executive tasks. 15 healthy controls and 25 persons with MS participated. Regression analyses were used to examine the relationship between executive functioning and FA, both before and after processing speed was removed from the executive scores. Before processing speed was removed from the executive scores, reduced FA was associated with poor performance on Color-Word Interference Test and Trail-Making Test in a diffuse network including corpus callosum and superior longitudinal fasciculus. However, once processing speed was removed, the relationship between executive functions and FA was no longer significant on the Trail Making test, and significantly reduced and more localized on the Color-Word Interference Test. PMID:23777468

  12. A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.

    Science.gov (United States)

    Lee, Jennifer E; Bisht, Babita; Hall, Michael J; Rubenstein, Linda M; Louison, Rebecca; Klein, Danielle T; Wahls, Terry L

    2017-01-01

    The objective of this study was to examine whether participation in a 12-month multimodal intervention would improve mood and cognitive function in adults with progressive multiple sclerosis (MS). In this one-arm, open-label feasibility trial, participants were prescribed a home-based multimodal intervention, including (1) a modified Paleolithic diet; (2) an exercise program (stretching and strengthening of the trunk and lower limb muscles); (3) neuromuscular electrical stimulation (EStim) of trunk and lower limb muscles; and (4) stress management (meditation and self-massage). Individuals completed measures of mood (Beck Anxiety and Depression Inventories) and cognitive (Cognitive Stability Index, Cognitive Screening Test, Delis-Kaplan Executive Function System) and executive function (Wechsler Adult Intelligence Scale) at baseline and 3, 6, 9, and 12 months after the start of the intervention. Dosage of the multimodal intervention was assessed at 3, 6, 9, and 12 months. The more individuals participated in the intervention activities, the greater improvements they had from baseline to 12 months on self-report measures of anxiety (Beck Anxiety Inventory [BAI]; ps = 0.001 to 0.02), depression (Beck Depression Inventory [BDI]; ps = Mood and cognitive improvements were more closely related to a higher intake of the modified Paleolithic diet than to exercise and stress management dosage. Anxiety and depression changes were evident after just a few months, whereas changes in cognitive function were generally not observed until later in the intervention period. Mood and cognitive function changes from baseline to 12 months were significantly associated with fatigue improvements (ps = exercise, EStim, and stress management intervention like this one has the potential to improve the mood and cognitive symptoms that can lead to considerable suffering in people with MS, potentially improving quality of life and function for people with progressive MS.

  13. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    Directory of Open Access Journals (Sweden)

    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  14. Evolution of the Black Hole Mass Function in Star Clusters from Multiple Mergers

    Science.gov (United States)

    Christian, Pierre; Mocz, Philip; Loeb, Abraham

    2018-05-01

    We investigate the effects of black hole (BH) mergers in star clusters on the black hole mass function (BHMF). As BHs are not produced in pair-instability supernovae, it is suggested that there is a dearth of high-mass stellar BHs. This dearth generates a gap in the upper end of the BHMF. Meanwhile, parameter fitting of X-ray binaries suggests the existence of a gap in the mass function under 5 solar masses. We show, through evolving a coagulation equation, that BH mergers can appreciably fill the upper mass gap, and that the lower mass gap generates potentially observable features at larger mass scales. We also explore the importance of ejections in such systems and whether dynamical clusters can be formation sites of intermediate-mass BH seeds.

  15. Towards an integration of biodiversity-ecosystem functioning and food web theory to evaluate relationships between multiple ecosystem services

    NARCIS (Netherlands)

    Hines, Jes; van der Putten, W.H.; De Deyn, G.B.; Wagg, Cameron; Voigt, Winfried; Mulder, Christian; Weisser, Wolfgang W.; Engel, Jan; Melian, Carlos; Scheu, Stefan; Birkhofer, Klaus; Ebeling, Anne; Scherber, Christoph; Eisenhauer, Nico

    2015-01-01

    Ecosystem responses to changes in species diversity are often studied individually. However, changes in species diversity can simultaneously influence multiple interdependent ecosystem functions. Therefore, an important challenge is to determine when and how changes in species diversity that

  16. Disrupted Module Efficiency of Structural and Functional Brain Connectomes in Clinically Isolated Syndrome and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Yaou Liu

    2018-04-01

    Full Text Available Recent studies have demonstrated disrupted topological organization of brain connectome in multiple sclerosis (MS. However, whether the communication efficiency between different functional systems is affected in the early stage of MS remained largely unknown. In this study, we constructed the structural connectivity (SC and functional connectivity (FC networks in 41 patients with clinically isolated syndrome (CIS, 32 MS patients and 35 healthy controls (HC based on diffusion and resting-state functional MRI. To quantify the communication efficiency within and between different functional systems, we proposed two measures called intra- and inter-module efficiency. Based on the module parcellation of functional backbone network, the intra- and inter-module efficiency of SC and FC networks was calculated for each participant. For the SC network, CIS showed decreased inter-module efficiency between the sensory-motor network (SMN, the visual network (VN, the default-mode network (DMN and the fronto-parietal network (FPN compared with HC, while MS showed more widespread decreased module efficiency both within and between modules relative to HC and CIS. For the FC network, no differences were found between CIS and HC, and a decreased inter-module efficiency between SMN and FPN and between VN and FPN was identified in MS, compared with HC and CIS. Moreover, both intra- and inter-module efficiency of SC network were correlated with the disability and cognitive scores in MS. Therefore, our results demonstrated early SC changes between modules in CIS, and more widespread SC alterations and inter-module FC changes were observed in MS, which were further associated with cognitive impairment and physical disability.

  17. Regulation of EphA4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function

    DEFF Research Database (Denmark)

    Egea, Joaquim; Nissen, Ulla Vig; Dufour, Audrey

    2005-01-01

    Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also...... requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4 EE), whose kinase is constitutively activated in the absence of ephrinB ligands......, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4EE, including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation...

  18. Multiple zeta functions and double wrapping in planar N=4 SYM

    Science.gov (United States)

    Leurent, Sébastien; Volin, Dmytro

    2013-10-01

    Using the FiNLIE solution of the AdS/CFT Y-system, we compute the anomalous dimension of the Konishi operator in planar N=4 SYM up to eight loops, i.e. up to the leading double wrapping order. At this order a non-reducible Euler-Zagier sum, ζ1,2,8, appears for the first time. We find that at all orders in perturbation, every spectral-dependent quantity of the Y-system is expressed through multiple Hurwitz zeta functions, hence we provide a Mathematica package to manipulate these functions, including the particular case of Euler-Zagier sums. Furthermore, we conjecture that only Euler-Zagier sums can appear in the answer for the anomalous dimension at any order in perturbation theory. We also resum the leading transcendentality terms of the anomalous dimension at all orders, obtaining a simple result in terms of Bessel functions. Finally, we demonstrate that exact Bethe equations should be related to an absence of poles condition that becomes especially non-trivial at double wrapping.

  19. Building a functional neurocognitive theory of the multiple intelligences anatomical framework

    Directory of Open Access Journals (Sweden)

    Carlo eCerruti

    2013-12-01

    Full Text Available A key goal of educational neuroscience is to conduct constrained experimental research that is theory-driven and yet also clearly related to educators’ complex set of questions and concerns. However, the fields of education, cognitive psychology and neuroscience use different levels of description to characterize human ability. An important advance in research in educational neuroscience would be the identification of a cognitive and neurocognitive framework at a level of description relatively intuitive to educators. I argue that the theory of multiple intelligences (Gardner, 1983, a conception of the mind that motivated a past generation of teachers, may provide such an opportunity. I criticize MI for doing little to clarify for teachers a core misunderstanding, specifically that MI was only an anatomical map of the mind but not a functional theory that detailed how the mind actually processes information. In an attempt to build a functional MI theory, I integrate into MI basic principles of cognitive and neural functioning, namely interregional neural facilitation and inhibition. In so doing I hope to forge a path towards constrained experimental research that bears upon teachers’ concerns about teaching and learning.

  20. Multiple genetic interaction experiments provide complementary information useful for gene function prediction.

    Directory of Open Access Journals (Sweden)

    Magali Michaut

    Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.

  1. Volatile terpenoids: multiple functions, biosynthesis, modulation and manipulation by genetic engineering.

    Science.gov (United States)

    Abbas, Farhat; Ke, Yanguo; Yu, Rangcai; Yue, Yuechong; Amanullah, Sikandar; Jahangir, Muhammad Muzammil; Fan, Yanping

    2017-11-01

    Terpenoids play several physiological and ecological functions in plant life through direct and indirect plant defenses and also in human society because of their enormous applications in the pharmaceutical, food and cosmetics industries. Through the aid of genetic engineering its role can by magnified to broad spectrum by improving genetic ability of crop plants, enhancing the aroma quality of fruits and flowers and the production of pharmaceutical terpenoids contents in medicinal plants. Terpenoids are structurally diverse and the most abundant plant secondary metabolites, playing an important role in plant life through direct and indirect plant defenses, by attracting pollinators and through different interactions between the plants and their environment. Terpenoids are also significant because of their enormous applications in the pharmaceutical, food and cosmetics industries. Due to their broad distribution and functional versatility, efforts are being made to decode the biosynthetic pathways and comprehend the regulatory mechanisms of terpenoids. This review summarizes the recent advances in biosynthetic pathways, including the spatiotemporal, transcriptional and post-transcriptional regulatory mechanisms. Moreover, we discuss the multiple functions of the terpene synthase genes (TPS), their interaction with the surrounding environment and the use of genetic engineering for terpenoid production in model plants. Here, we also provide an overview of the significance of terpenoid metabolic engineering in crop protection, plant reproduction and plant metabolic engineering approaches for pharmaceutical terpenoids production and future scenarios in agriculture, which call for sustainable production platforms by improving different plant traits.

  2. Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

    Science.gov (United States)

    Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

    2016-01-01

    Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

  3. Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis

    Directory of Open Access Journals (Sweden)

    Chelsea M. Stillman

    2016-12-01

    Full Text Available Physical activity (PA is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

  4. Functional Brain Connectivity during Multiple Motor Imagery Tasks in Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Alkinoos Athanasiou

    2018-01-01

    Full Text Available Reciprocal communication of the central and peripheral nervous systems is compromised during spinal cord injury due to neurotrauma of ascending and descending pathways. Changes in brain organization after spinal cord injury have been associated with differences in prognosis. Changes in functional connectivity may also serve as injury biomarkers. Most studies on functional connectivity have focused on chronic complete injury or resting-state condition. In our study, ten right-handed patients with incomplete spinal cord injury and ten age- and gender-matched healthy controls performed multiple visual motor imagery tasks of upper extremities and walking under high-resolution electroencephalography recording. Directed transfer function was used to study connectivity at the cortical source space between sensorimotor nodes. Chronic disruption of reciprocal communication in incomplete injury could result in permanent significant decrease of connectivity in a subset of the sensorimotor network, regardless of positive or negative neurological outcome. Cingulate motor areas consistently contributed the larger outflow (right and received the higher inflow (left among all nodes, across all motor imagery categories, in both groups. Injured subjects had higher outflow from left cingulate than healthy subjects and higher inflow in right cingulate than healthy subjects. Alpha networks were less dense, showing less integration and more segregation than beta networks. Spinal cord injury patients showed signs of increased local processing as adaptive mechanism. This trial is registered with NCT02443558.

  5. Feasibility study for remote assessment of cognitive function in multiple sclerosis.

    Science.gov (United States)

    George, Michaela F; Holingue, Calliope B; Briggs, Farren B S; Shao, Xiaorong; Bellesis, Kalliope H; Whitmer, Rachel A; Schaefer, Catherine; Benedict, Ralph Hb; Barcellos, Lisa F

    2016-01-01

    Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (pTICS-M score among cases (pTICS-M score was significantly lower in cases compared to controls (p=0.007). Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

  6. Deformable microparticles with multiple functions for drug delivery and device testing

    Science.gov (United States)

    Thula, Taili T.

    Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of

  7. Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

    Directory of Open Access Journals (Sweden)

    Justin A. Roby

    2014-01-01

    Full Text Available Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV, Japanese encephalitis virus (JEV, yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA derived from the 3' untranslated region (UTR. sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.

  8. Multiple gcd-closed sets and determinants of matrices associated with arithmetic functions

    Directory of Open Access Journals (Sweden)

    Hong Siao

    2016-01-01

    Full Text Available Let f be an arithmetic function and S = {x1, …, xn} be a set of n distinct positive integers. By (f(xi, xj (resp. (f[xi, xj] we denote the n × n matrix having f evaluated at the greatest common divisor (xi, xj (resp. the least common multiple [xi, xj] of x, and xj as its (i, j-entry, respectively. The set S is said to be gcd closed if (xi, xj ∈ S for 1 ≤ i, j ≤ n. In this paper, we give formulas for the determinants of the matrices (f(xi, xj and (f[xi, xj] if S consists of multiple coprime gcd-closed sets (i.e., S equals the union of S1, …, Sk with k ≥ 1 being an integer and S1, …, Sk being gcd-closed sets such that (lcm(Si, lcm(Sj = 1 for all 1 ≤ i ≠ j ≤ k. This extends the Bourque-Ligh, Hong’s and the Hong-Loewy formulas obtained in 1993, 2002 and 2011, respectively. It also generalizes the famous Smith’s determinant.

  9. Multiple functions of a multi-component mating pheromone in sea lamprey Petromyzon marinus

    Science.gov (United States)

    Johnson, N.S.; Yun, S.-S.; Buchinger, T.J.; Li, W.

    2012-01-01

    The role of the C24 sulphate in the mating pheromone component, 7α,12α,24-trihydroxy-5α-cholan-3-one 24-sulphate (3kPZS), to specifically induce upstream movement in ovulated female sea lampreys Petromyzon marinus was investigated. 7α,12α-dihydroxy-5α-cholan-3-one 24-oic acid (3kACA), a structurally similar bile acid released by spermiated males, but lacking the C24 sulphate ester, was tested in bioassays at concentrations between 10−11 and 10−14 molar (M). 3kACA did not induce upstream movement in females or additional reproductive behaviours. In contrast, spermiated male washings induced upstream movement, prolonged retention on a nest and induced an array of nesting behaviours. Differential extraction and elution by solid-phase extraction resins showed that components other than 3kPZS + 3kACA are necessary to retain females on nests and induce nest cleaning behaviours. All pheromone components, including components in addition to 3kPZS + 3kACA that retain females and induce nest cleaning behaviours were released from the anterior region of the males, as had been reported for 3kPZS. It is concluded that the sea lamprey male mating pheromone has multiple functions and is composed of multiple components.

  10. Heavy-flavour production as a function of multiplicity in pp collisions at ALICE

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    The measurement of inclusive heavy-flavour production cross sections in proton-proton (pp) collisions at LHC energies constituted an important test of perturbative QCD calculations. The measured cross sections can be described within uncertainties by next-to-leading order (NLO) and fixed-order with next-to-leading-log re-summation (FONLL) calculations with collinear factorization, as well as by leading-order (LO) calculations in the kt-factorization approach. More differential measurements of charm and beauty production in pp collisions can provide further information about the particle production mechanisms. The production of prompt D mesons and non-prompt J/psi mesons in proton-proton collisions at a centre-of-mass energy of 7 TeV was measured by the ALICE Collaboration as a function of the multiplicity of charged particles produced in the collision. D0, D+ and D*+ mesons were reconstructed from their hadronic decay channels in the central rapidity region and their yields were measured in different multipl...

  11. Development of particle multiplicity distributions using a general form of the grand canonical partition function

    International Nuclear Information System (INIS)

    Lee, S.J.; Mekjian, A.Z.

    2004-01-01

    Various phenomenological models of particle multiplicity distributions are discussed using a general form of a unified model which is based on the grand canonical partition function and Feynman's path integral approach to statistical processes. These models can be written as special cases of a more general distribution which has three control parameters which are a,x,z. The relation to these parameters to various physical quantities are discussed. A connection of the parameter a with Fisher's critical exponent τ is developed. Using this grand canonical approach, moments, cumulants and combinants are discussed and a physical interpretation of the combinants are given and their behavior connected to the critical exponent τ. Various physical phenomena such as hierarchical structure, void scaling relations, Koba-Nielson-Olesen or KNO scaling features, clan variables, and branching laws are shown in terms of this general approach. Several of these features which were previously developed in terms of the negative binomial distribution are found to be more general. Both hierarchical structure and void scaling relations depend on the Fisher exponent τ. Applications of our approach to the charged particle multiplicity distribution in jets of L3 and H1 data are given

  12. Multiple Time Series Forecasting Using Quasi-Randomized Functional Link Neural Networks

    Directory of Open Access Journals (Sweden)

    Thierry Moudiki

    2018-03-01

    Full Text Available We are interested in obtaining forecasts for multiple time series, by taking into account the potential nonlinear relationships between their observations. For this purpose, we use a specific type of regression model on an augmented dataset of lagged time series. Our model is inspired by dynamic regression models (Pankratz 2012, with the response variable’s lags included as predictors, and is known as Random Vector Functional Link (RVFL neural networks. The RVFL neural networks have been successfully applied in the past, to solving regression and classification problems. The novelty of our approach is to apply an RVFL model to multivariate time series, under two separate regularization constraints on the regression parameters.

  13. Estimation of Multiple Point Sources for Linear Fractional Order Systems Using Modulating Functions

    KAUST Repository

    Belkhatir, Zehor

    2017-06-28

    This paper proposes an estimation algorithm for the characterization of multiple point inputs for linear fractional order systems. First, using polynomial modulating functions method and a suitable change of variables the problem of estimating the locations and the amplitudes of a multi-pointwise input is decoupled into two algebraic systems of equations. The first system is nonlinear and solves for the time locations iteratively, whereas the second system is linear and solves for the input’s amplitudes. Second, closed form formulas for both the time location and the amplitude are provided in the particular case of single point input. Finally, numerical examples are given to illustrate the performance of the proposed technique in both noise-free and noisy cases. The joint estimation of pointwise input and fractional differentiation orders is also presented. Furthermore, a discussion on the performance of the proposed algorithm is provided.

  14. Computer Simulations Reveal Multiple Functions for Aromatic Residues in Cellulase Enzymes (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-07-01

    NREL researchers use high-performance computing to demonstrate fundamental roles of aromatic residues in cellulase enzyme tunnels. National Renewable Energy Laboratory (NREL) computer simulations of a key industrial enzyme, the Trichoderma reesei Family 6 cellulase (Cel6A), predict that aromatic residues near the enzyme's active site and at the entrance and exit tunnel perform different functions in substrate binding and catalysis, depending on their location in the enzyme. These results suggest that nature employs aromatic-carbohydrate interactions with a wide variety of binding affinities for diverse functions. Outcomes also suggest that protein engineering strategies in which mutations are made around the binding sites may require tailoring specific to the enzyme family. Cellulase enzymes ubiquitously exhibit tunnels or clefts lined with aromatic residues for processing carbohydrate polymers to monomers, but the molecular-level role of these aromatic residues remains unknown. In silico mutation of the aromatic residues near the catalytic site of Cel6A has little impact on the binding affinity, but simulation suggests that these residues play a major role in the glucopyranose ring distortion necessary for cleaving glycosidic bonds to produce fermentable sugars. Removal of aromatic residues at the entrance and exit of the cellulase tunnel, however, dramatically impacts the binding affinity. This suggests that these residues play a role in acquiring cellulose chains from the cellulose crystal and stabilizing the reaction product, respectively. These results illustrate that the role of aromatic-carbohydrate interactions varies dramatically depending on the position in the enzyme tunnel. As aromatic-carbohydrate interactions are present in all carbohydrate-active enzymes, the results have implications for understanding protein structure-function relationships in carbohydrate metabolism and recognition, carbon turnover in nature, and protein engineering

  15. The relationship between multiple joint flexibility and functional performance in independent and physically active elderly women

    Directory of Open Access Journals (Sweden)

    Maria Joana de Carvalho

    2007-09-01

    Full Text Available Multi-joint flexibility assessment seems to be more appropriate for analyzing the association between fl exibility and functional fitness, but there is a lack of studies to confi rm this possibility in elderly people. The present study investigated the relationship between a multiple joint fl exibility assessment and the functional performance of 30 independent and physically active elderly women (age=68±1yr. Flexibility was assessed using the Chair Sit-and-Reach Test (CSRT. Functional performance was tested by a combination of three tasks: a Step Length (SL; b Time to Put on Sneakers (TPS; c Climbing Stairs (CS. The association between fl exibility and functional performance was tested by both simple and multiple correlation techniques. Pearson’s correlation was signifi cant for TPS (r = -.37; p ABSTRACT

  16. Open to Suggestion.

    Science.gov (United States)

    Journal of Reading, 1987

    1987-01-01

    Offers (1) suggestions for improving college students' study skills; (2) a system for keeping track of parent, teacher, and community contacts; (3) suggestions for motivating students using tic tac toe; (4) suggestions for using etymology to improve word retention; (5) a word search grid; and (6) suggestions for using postcards in remedial reading…

  17. Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

    Science.gov (United States)

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

  18. Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

    Science.gov (United States)

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

  19. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

    Science.gov (United States)

    McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

    2015-10-13

    The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases

  20. In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function.

    Science.gov (United States)

    Follin, Elna; Karlsson, Maria; Lundegaard, Claus; Nielsen, Morten; Wallin, Stefan; Paulsson, Kajsa; Westerdahl, Helena

    2013-04-01

    The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1-α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their functional and genetic relationships. We found more pronounced clustering of the MHC class I allomorphs (allele specific proteins) in regards to their function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrow and great reed warbler, although these species diverged 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be ruled out.

  1. Impulsivity, self-control, and hypnotic suggestibility.

    Science.gov (United States)

    Ludwig, V U; Stelzel, C; Krutiak, H; Prunkl, C E; Steimke, R; Paschke, L M; Kathmann, N; Walter, H

    2013-06-01

    Hypnotic responding might be due to attenuated frontal lobe functioning after the hypnotic induction. Little is known about whether personality traits linked with frontal functioning are associated with responsiveness to hypnotic suggestions. We assessed whether hypnotic suggestibility is related to the traits of self-control and impulsivity in 154 participants who completed the Brief Self-Control Scale, the Self-Regulation Scale, the Barratt Impulsiveness Scale (BIS-11), and the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A). BIS-11 non-planning impulsivity correlated positively with HGSHS:A (Bonferroni-corrected). Furthermore, in the best model emerging from a stepwise multiple regression, both non-planning impulsivity and self-control positively predicted hypnotic suggestibility, and there was an interaction of BIS-11 motor impulsivity with gender. For men only, motor impulsivity tended to predict hypnotic suggestibility. Hypnotic suggestibility is associated with personality traits linked with frontal functioning, and hypnotic responding in men and women might differ. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

    International Nuclear Information System (INIS)

    Umezu, K.; Sugawara, N.; Chen, C.; Haber, J.E.; Kolodner, R.D.

    1998-01-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10 4 to 10 5 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

  3. Skin and scales of teleost fish: Simple structure but high performance and multiple functions

    Science.gov (United States)

    Vernerey, Franck J.; Barthelat, Francois

    2014-08-01

    Natural and man-made structural materials perform similar functions such as structural support or protection. Therefore they rely on the same types of properties: strength, robustness, lightweight. Nature can therefore provide a significant source of inspiration for new and alternative engineering designs. We report here some results regarding a very common, yet largely unknown, type of biological material: fish skin. Within a thin, flexible and lightweight layer, fish skins display a variety of strain stiffening and stabilizing mechanisms which promote multiple functions such as protection, robustness and swimming efficiency. We particularly discuss four important features pertaining to scaled skins: (a) a strongly elastic tensile behavior that is independent from the presence of rigid scales, (b) a compressive response that prevents buckling and wrinkling instabilities, which are usually predominant for thin membranes, (c) a bending response that displays nonlinear stiffening mechanisms arising from geometric constraints between neighboring scales and (d) a robust structure that preserves the above characteristics upon the loss or damage of structural elements. These important properties make fish skin an attractive model for the development of very thin and flexible armors and protective layers, especially when combined with the high penetration resistance of individual scales. Scaled structures inspired by fish skin could find applications in ultra-light and flexible armor systems, flexible electronics or the design of smart and adaptive morphing structures for aerospace vehicles.

  4. Stroop performance in multiple sclerosis: information processing, selective attention, or executive functioning?

    Science.gov (United States)

    Macniven, J A B; Davis, C; Ho, M-Y; Bradshaw, C M; Szabadi, E; Constantinescu, C S

    2008-09-01

    Cognitive impairments in information processing speed, attention and executive functioning are widely reported in patients with multiple sclerosis (MS). Several studies have identified impaired performance on the Stroop test in people with MS, yet uncertainty remains over the cause of this phenomenon. In this study, 25 patients with MS were assessed with a neuropsychological test battery including a computerized Stroop test and a computerized test of information processing speed, the Graded Conditional Discrimination Tasks (GCDT). The patient group was compared with an individually age, sex and estimated premorbid IQ-matched healthy control group. The patients' reaction times (RTs) were significantly longer than those of the controls on all Stroop test trials and there was a significantly enhanced absolute (RT(incongruent)-RT(neutral)) and relative (100 x [RT(incongruent)-RT(neutral)]/RT(neutral)) Stroop interference effect for the MS group. The linear function relating RT to stimulus complexity in the GCDT was significantly steeper in the patient group, indicating slowed information processing. The results are discussed with reference to the difference engine model, a theory of diversity in speeded cognition. It is concluded that, in the assessment of people with MS, great caution must be used in the interpretation of performance on neuropsychological tests which rely on RT as the primary measure.

  5. Freezing of enkephalinergic functions by multiple noxious foci: a source of pain sensitization?

    Directory of Open Access Journals (Sweden)

    François Cesselin

    Full Text Available BACKGROUND: The functional significance of proenkephalin systems in processing pain remains an open question and indeed is puzzling. For example, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM from segments of the spinal cord related to the stimulated area of the body, but does increase its release from other segments. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that, in the rat, a noxious mechanical stimulus applied to either the right or the left hind paw elicits a marked increase of MELM release during perifusion of either the whole spinal cord or the cervico-trigeminal area. However, these stimulatory effects were not additive and indeed, disappeared completely when the right and left paws were stimulated simultaneously. CONCLUSION/SIGNIFICANCE: We have concluded that in addition to the concept of a diffuse control of the transmission of nociceptive signals through the dorsal horn, there is a diffuse control of the modulation of this transmission. The "freezing" of Met-enkephalinergic functions represents a potential source of central sensitization in the spinal cord, notably in clinical situations involving multiple painful foci, e.g. cancer with metastases, poly-traumatism or rheumatoid arthritis.

  6. Suicidality and interrogative suggestibility.

    Science.gov (United States)

    Pritchard-Boone, Lea; Range, Lillian M

    2005-01-01

    All people are subject to memory suggestibility, but suicidal individuals may be especially so. The link between suicidality and suggestibility is unclear given mixed findings and methodological weaknesses of past research. To test the link between suicidality and interrogative suggestibility, 149 undergraduates answered questions about suicidal thoughts and reasons for living, and participated in a direct suggestibility procedure. As expected, suggestibility correlated with suicidality but accounted for little overall variance (4%). Mental health professionals might be able to take advantage of client suggestibility by directly telling suicidal persons to refrain from suicidal thoughts or actions.

  7. Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose.

    Science.gov (United States)

    Paithankar, Jagdish Gopal; Raghu, Shamprasad Varija; Patil, Rajashekhar K

    2018-04-20

    During development, various life stages of Drosophila melanogaster (D. melanogaster) show different levels of resistance to gamma irradiation, with the early pupal stage being the most radiation sensitive. This provides us an opportunity to explore the biochemical basis of such variations. The present study was carried out to understand the mechanisms underlying radiation resistance during life stages of D. melanogaster. Homogenates from all the life stages of D. melanogaster were prepared at stipulated age. These homogenates were used for the determination of (1) enzymatic antioxidants: superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx), and glutathione S-transferase (GST); (2) reducing non-enzymatic antioxidants: total antioxidant capacity (TAC), reduced glutathione (GSH) and non-reducing non-enzymatic antioxidant trehalose; and (3) levels of protein carbonyl (PC) content. Age-dependent changes in radiation resistance and associated biochemical changes were also studied in young (2 d) and old (20 and 30 d) flies. TAC and GSH were found high in the early pupal stage, whereas catalase and DmGPx were found to increase in the early pupal stage. The non-feeding third instar (NFTI) larvae were found to have high levels of SOD and GST, besides NFTI larvae showed high levels of trehalose. A remarkable decrease was observed in radiation resistance and trehalose levels during the early pupal stage. The PC level was the highest during early pupal stage and was the lowest in NFTI larvae. Older flies showed high level of PC compared with young flies. In vitro increments in trehalose concentration correspond to reduced formation of PCs, suggesting a protective role of trehalose against free radicals. A strong correlation between levels of trehalose and PC formation suggests amelioration of proteome damage due to ionizing radiation (IR). Stages with high trehalose levels showed protected proteome and high radiation resistance, suggesting a

  8. Loss of Niemann-Pick C1 or C2 protein results in similar biochemical changes suggesting that these proteins function in a common lysosomal pathway.

    Directory of Open Access Journals (Sweden)

    Sayali S Dixit

    Full Text Available Niemann-Pick Type C (NPC disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal cholesterol with both proteins binding cholesterol in vitro but they may have unrelated lysosomal roles. To investigate this possibility, we compared biochemical consequences of the loss of either protein. Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. The subcellular distribution of both proteins was similar and paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted in similar alterations in the carbohydrate processing of the lysosomal protease, tripeptidyl peptidase I. These results highlight biochemical alterations in the lysosomal system of the NPC-mutant mice that appear secondary to lipid storage. In addition, the similarity in biochemical phenotypes resulting from either NPC1 or NPC2 deficiency supports models in which the function of these two proteins within lysosomes are linked closely.

  9. Multiple cluster axis II comorbidity and functional outcome in severe patients with borderline personality disorder.

    Science.gov (United States)

    Palomares, Nerea; McMaster, Antonia; Díaz-Marsá, Marina; de la Vega, Irene; Montes, Ana; Carrasco, José Luis

    2016-11-01

    Current literature suggests that personality disorder comorbidity negatively contributes to both the severity and prognosis of other disorders; however, little literature has been devoted to its influence on borderline personality disorder (BPD). The objective of the present work is to study comorbidity with other personality disorders in a severe clinical sample of patients with BPD, and its relationship with global functionality. A sample of 65 patients with severe borderline personality disorder was included in the study. Clinical and functionality measures were applied in order to study comorbidity of BPD with other disorders and its relationship with functionality. Associations with other comorbid PDs were analyzed with t-tests and linear correlations. Most patients (87%) presented comorbidity with other PDs. Almost half of the sample (42%) presented more than two PDs, and cluster A (paranoid) and C (obsessive and avoidant) PD were more frequent than cluster B (histrionic and antisocial). Only the presence of avoidant PD predicted a worse functional outcome in the long term (U Mann Withney ppersonality disorder might negatively predict for prognosis.

  10. RhoGDI: multiple functions in the regulation of Rho family GTPase activities

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability...... insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... of activities....

  11. The Armeo Spring as training tool to improve upper limb functionality in multiple sclerosis: a pilot study

    Directory of Open Access Journals (Sweden)

    Kerkhofs Lore

    2011-01-01

    Full Text Available Abstract Background Few research in multiple sclerosis (MS has focused on physical rehabilitation of upper limb dysfunction, though the latter strongly influences independent performance of activities of daily living. Upper limb rehabilitation technology could hold promise for complementing traditional MS therapy. Consequently, this pilot study aimed to examine the feasibility of an 8-week mechanical-assisted training program for improving upper limb muscle strength and functional capacity in MS patients with evident paresis. Methods A case series was applied, with provision of a training program (3×/week, 30 minutes/session, supplementary on the customary maintaining care, by employing a gravity-supporting exoskeleton apparatus (Armeo Spring. Ten high-level disability MS patients (Expanded Disability Status Scale 7.0-8.5 actively performed task-oriented movements in a virtual real-life-like learning environment with the affected upper limb. Tests were administered before and after training, and at 2-month follow-up. Muscle strength was determined through the Motricity Index and Jamar hand-held dynamometer. Functional capacity was assessed using the TEMPA, Action Research Arm Test (ARAT and 9-Hole Peg Test (9HPT. Results Muscle strength did not change significantly. Significant gains were particularly found in functional capacity tests. After training completion, TEMPA scores improved (p = 0.02, while a trend towards significance was found for the 9HPT (p = 0.05. At follow-up, the TEMPA as well as ARAT showed greater improvement relative to baseline than after the 8-week intervention period (p = 0.01, p = 0.02 respectively. Conclusions The results of present pilot study suggest that upper limb functionality of high-level disability MS patients can be positively influenced by means of a technology-enhanced physical rehabilitation program.

  12. Relationship between muscle strength parameters and functional capacity in persons with mild to moderate degree multiple sclerosis

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Vissing, Kristian; Langeskov-Christensen, Daniel

    2015-01-01

    BACKGROUND: Maximal muscle strength has been shown to be an important predictor of functional capacity for persons with multiple sclerosis (PwMS). Another muscle strength parameter known to be important for functional capacity in other patient groups is rate of force development (RFD) in knee...... is the better predictor of walking performance in persons with mild to moderate multiple sclerosis. RFD, although also important for functional capacity, is a less strong predictor. Maximal strength of the knee extensors, rather than the knee flexors, predicted performance in the stairclimb and 5STS tests....

  13. Multiple amino acid sequence alignment nitrogenase component 1: insights into phylogenetics and structure-function relationships.

    Directory of Open Access Journals (Sweden)

    James B Howard

    Full Text Available Amino acid residues critical for a protein's structure-function are retained by natural selection and these residues are identified by the level of variance in co-aligned homologous protein sequences. The relevant residues in the nitrogen fixation Component 1 α- and β-subunits were identified by the alignment of 95 protein sequences. Proteins were included from species encompassing multiple microbial phyla and diverse ecological niches as well as the nitrogen fixation genotypes, anf, nif, and vnf, which encode proteins associated with cofactors differing at one metal site. After adjusting for differences in sequence length, insertions, and deletions, the remaining >85% of the sequence co-aligned the subunits from the three genotypes. Six Groups, designated Anf, Vnf , and Nif I-IV, were assigned based upon genetic origin, sequence adjustments, and conserved residues. Both subunits subdivided into the same groups. Invariant and single variant residues were identified and were defined as "core" for nitrogenase function. Three species in Group Nif-III, Candidatus Desulforudis audaxviator, Desulfotomaculum kuznetsovii, and Thermodesulfatator indicus, were found to have a seleno-cysteine that replaces one cysteinyl ligand of the 8Fe:7S, P-cluster. Subsets of invariant residues, limited to individual groups, were identified; these unique residues help identify the gene of origin (anf, nif, or vnf yet should not be considered diagnostic of the metal content of associated cofactors. Fourteen of the 19 residues that compose the cofactor pocket are invariant or single variant; the other five residues are highly variable but do not correlate with the putative metal content of the cofactor. The variable residues are clustered on one side of the cofactor, away from other functional centers in the three dimensional structure. Many of the invariant and single variant residues were not previously recognized as potentially critical and their identification

  14. Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.

    Science.gov (United States)

    Meijer, Kim A; Eijlers, Anand J C; Geurts, Jeroen J G; Schoonheim, Menno M

    2018-02-01

    Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Multiple roles of the extracellular vestibule amino acid residues in the function of the rat P2X4 receptor.

    Directory of Open Access Journals (Sweden)

    Milos B Rokic

    Full Text Available The binding of ATP to trimeric P2X receptors (P2XR causes an enlargement of the receptor extracellular vestibule, leading to opening of the cation-selective transmembrane pore, but specific roles of vestibule amino acid residues in receptor activation have not been evaluated systematically. In this study, alanine or cysteine scanning mutagenesis of V47-V61 and F324-N338 sequences of rat P2X4R revealed that V49, Y54, Q55, F324, and G325 mutants were poorly responsive to ATP and trafficking was only affected by the V49 mutation. The Y54F and Y54W mutations, but not the Y54L mutation, rescued receptor function, suggesting that an aromatic residue is important at this position. Furthermore, the Y54A and Y54C receptor function was partially rescued by ivermectin, a positive allosteric modulator of P2X4R, suggesting a rightward shift in the potency of ATP to activate P2X4R. The Q55T, Q55N, Q55E, and Q55K mutations resulted in non-responsive receptors and only the Q55E mutant was ivermectin-sensitive. The F324L, F324Y, and F324W mutations also rescued receptor function partially or completely, ivermectin action on channel gating was preserved in all mutants, and changes in ATP responsiveness correlated with the hydrophobicity and side chain volume of the substituent. The G325P mutant had a normal response to ATP, suggesting that G325 is a flexible hinge. A topological analysis revealed that the G325 and F324 residues disrupt a β-sheet upon ATP binding. These results indicate multiple roles of the extracellular vestibule amino acid residues in the P2X4R function: the V49 residue is important for receptor trafficking to plasma membrane, the Y54 and Q55 residues play a critical role in channel gating and the F324 and G325 residues are critical for vestibule widening.

  16. Evaluation of reach and grasp robot-assisted therapy suggests similar functional recovery patterns on proximal and distal arm segments in sub-acute hemiplegia.

    Science.gov (United States)

    Loureiro, Rui C V; Harwin, William S; Lamperd, Robert; Collin, Christine

    2014-05-01

    This paper provides some additional evidence in support of the hypothesis that robot therapies are clinically beneficial in neurorehabilitation. Although only four subjects were included in the study, the design of the intervention and the measures were done so as to minimize bias. The results are presented as single case studies, and can only be interpreted as such due to the study size. The intensity of intervention was 16 h and the therapy philosophy (based on Carr and Shepherd) was that coordinated movements are preferable to joint based therapies, and that coordinating distal movements (in this case grasps) helps not only to recover function in these areas, but has greater value since the results are immediately transferable to daily skills such as reach and grasp movements.

  17. Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.

    Directory of Open Access Journals (Sweden)

    Stephanie Kuhn

    Full Text Available Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21 in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+ currents characteristic of control hair cells. However, the size of the large conductance (BK Ca(2+ activated K(+ current (I(K,f, which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.

  18. Prefrontal Function Engaging in External-Focused Attention in 5- to 6-Month-Old Infants: A Suggestion for Default Mode Network.

    Science.gov (United States)

    Xu, Mingdi; Hoshino, Eiichi; Yatabe, Kiyomi; Matsuda, Soichiro; Sato, Hiroki; Maki, Atsushi; Yoshimura, Mina; Minagawa, Yasuyo

    2016-01-01

    The present study used functional near-infrared spectroscopy (fNIRS) to measure 5- to 6-month-old infants' hemodynamic response in the prefrontal cortex (PFC) to visual stimuli differing in saliency and social value. Nineteen Japanese 5- to 6-month-old infants watched video clips of Peek-a-Boo (social signal) performed by an anime character (AC) or a human, and hand movements without social signal performed by an AC. The PFC activity of infants was measured by 22-channel fNIRS, while behaviors including looking time were recorded simultaneously. NIRS data showed that infants' hemodynamic responses in the PFC generally decreased due to these stimuli, and the decrease was most prominent in the frontopolar (FP), covering medial PFC (MPFC), when infants were viewing Peek-a-Boo performed by an AC. Moreover, the decrease was more pronounced in the dorsolateral PFC (DLPFC) when infants were viewing Peek-a-Boo performed by an AC than by a human. Accordingly, behavioral data revealed significantly longer looking times when Peek-a-Boo was performed by an AC than by a human. No significant difference between Peek-a-Boo and non-Peek-a-Boo conditions was observed in either measure. These findings indicate that infants at this age may prefer stimuli with more salient features, which may be more effective in attracting their attentions. In conjunction with our previous findings on responses to self-name calling in infants of similar age, we hypothesize that the dynamic function of the MPFC and its vicinity (as part of default mode network (DMN): enhanced by self-focused stimuli, attenuated by externally focused stimuli), which is consistently observed in adults, may have already emerged in 5- to 6-month-old infants.

  19. Mechanism for the reaction of 2-naphthol with N-methyl-N-phenyl-hydrazine suggested by the density functional theory investigations.

    Science.gov (United States)

    Gao, Jie Ying; Zhang, Cheng Hua; Luo, Mei Ming; Kim, Chan Kyung; Chu, Wei; Xue, Ying

    2012-01-15

    For the first time the computed mechanisms for the novel reaction of 2-naphthol with N-methyl-N-phenylhydrazine, leading to 1-amino-2-naphthol (Tang et al., J Am Chem Soc 2008, 130, 5840), have been investigated using the density functional theory. Four distinct possible pathways were evaluated: two amination mechanisms with the attack of NH(2) group respectively at the α-position C1 and β-position C3 atoms of 2-naphthol (pathways 1 and 2) as well as two rearrangement processes with displacement of the phenolic hydroxyl group followed by the benzidine-like rearrangement at the α-position C1 and β-position C3 atoms of 2-naphthol, respectively (pathways 3 and 4). Solvent effect has been tested based on the optimized geometries of the stationary points in solution at the B3LYP/PCM/6-31+G(d,p) level of theory with an averaged dielectric constant of binary solvent. Single-point energies of the optimized structures have been calculated using three hybrid density functionals, B3LYP, MPW3LYP, and B3PW91 with the 6-311++G(3df,2p) basis set. Our computed results clearly manifest that pathway 1 (α-amination) has the highest possibility to occur, with the Gibbs free energies being lower by 6 to 20 kcal/mol compared with the other three pathways, which leads to 1-amino-2-naphthol and N-methylaniline as products. It is in excellent agreement with the experimental observation. Copyright © 2011 Wiley Periodicals, Inc.

  20. Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren's syndrome.

    Science.gov (United States)

    Johar, Angad S; Mastronardi, Claudio; Rojas-Villarraga, Adriana; Patel, Hardip R; Chuah, Aaron; Peng, Kaiman; Higgins, Angela; Milburn, Peter; Palmer, Stephanie; Silva-Lara, Maria Fernanda; Velez, Jorge I; Andrews, Dan; Field, Matthew; Huttley, Gavin; Goodnow, Chris; Anaya, Juan-Manuel; Arcos-Burgos, Mauricio

    2015-06-02

    Multiple autoimmune syndrome (MAS), an extreme phenotype of autoimmune disorders, is a very well suited trait to tackle genomic variants of these conditions. Whole exome sequencing (WES) is a widely used strategy for detection of protein coding and splicing variants associated with inherited diseases. The DNA of eight patients affected by MAS [all of whom presenting with Sjögren's syndrome (SS)], four patients affected by SS alone and 38 unaffected individuals, were subject to WES. Filters to identify novel and rare functional (pathogenic-deleterious) homozygous and/or compound heterozygous variants in these patients and controls were applied. Bioinformatics tools such as the Human gene connectome as well as pathway and network analysis were applied to test overrepresentation of genes harbouring these variants in critical pathways and networks involved in autoimmunity. Eleven novel and rare functional variants were identified in cases but not in controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, and FKRP. These were subsequently subject to network analysis and their functional relatedness to genes already associated with autoimmunity was evaluated. Notably, the LRP1/STAT6 novel mutation was homozygous in one MAS affected patient and heterozygous in another. LRP1/STAT6 disclosed the strongest plausibility for autoimmunity. LRP1/STAT6 are involved in extracellular and intracellular anti-inflammatory pathways that play key roles in maintaining the homeostasis of the immune system. Further; networks, pathways, and interaction analyses showed that LRP1 is functionally related to the HLA-B and IL10 genes and it has a substantial impact within immunological pathways and/or reaction to bacterial and other foreign proteins (phagocytosis, regulation of phospholipase A2 activity, negative regulation of apoptosis and response to lipopolysaccharides). Further, ICA1 and STAT6 were also closely related to AIRE and IRF5, two very

  1. Evolution of the stellar mass function in multiple-population globular clusters

    Science.gov (United States)

    Vesperini, Enrico; Hong, Jongsuk; Webb, Jeremy J.; D'Antona, Franca; D'Ercole, Annibale

    2018-05-01

    We present the results of a survey of N-body simulations aimed at studying the effects of the long-term dynamical evolution on the stellar mass function (MF) of multiple stellar populations in globular clusters. Our simulations show that if first-(1G) and second-generation (2G) stars have the same initial MF (IMF), the global MFs of the two populations are affected similarly by dynamical evolution and no significant differences between the 1G and 2G MFs arise during the cluster's evolution. If the two populations have different IMFs, dynamical effects do not completely erase memory of the initial differences. Should observations find differences between the global 1G and 2G MFs, these would reveal the fingerprints of differences in their IMFs. Irrespective of whether the 1G and 2G populations have the same global IMF or not, dynamical effects can produce differences between the local (measured at various distances from the cluster centre) 1G and 2G MFs; these differences are a manifestation of the process of mass segregation in populations with different initial structural properties. In dynamically old and spatially mixed clusters, however, differences between the local 1G and 2G MFs can reveal differences between the 1G and 2G global MFs. In general, for clusters with any dynamical age, large differences between the local 1G and 2G MFs are more likely to be associated with differences in the global MF. Our study also reveals a dependence of the spatial mixing rate on the stellar mass, another dynamical consequence of the multiscale nature of multiple-population clusters.

  2. Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways.

    Science.gov (United States)

    Neubrand, Veronika E; Cesca, Fabrizia; Benfenati, Fabio; Schiavo, Giampietro

    2012-04-15

    An increasing body of evidence suggests that several membrane receptors--in addition to activating distinct signalling cascades--also engage in substantial crosstalk with each other, thereby adjusting their signalling outcome as a function of specific input information. However, little is known about the molecular mechanisms that control their coordination and integration of downstream signalling. A protein that is likely to have a role in this process is kinase-D-interacting substrate of 220 kDa [Kidins220, also known as ankyrin repeat-rich membrane spanning (ARMS), hereafter referred to as Kidins220/ARMS]. Kidins220/ARMS is a conserved membrane protein that is preferentially expressed in the nervous system and interacts with the microtubule and actin cytoskeleton. It interacts with neurotrophin, ephrin, vascular endothelial growth factor (VEGF) and glutamate receptors, and is a common downstream target of several trophic stimuli. Kidins220/ARMS is required for neuronal differentiation and survival, and its expression levels modulate synaptic plasticity. Kidins220/ARMS knockout mice show developmental defects mainly in the nervous and cardiovascular systems, suggesting a crucial role for this protein in modulating the cross talk between different signalling pathways. In this Commentary, we summarise existing knowledge regarding the physiological functions of Kidins220/ARMS, and highlight some interesting directions for future studies on the role of this protein in health and disease.

  3. Scale breaking parton fragmentation functions, analytical parametrizations and comparison with charged multiplicities in e+e- annihilation

    International Nuclear Information System (INIS)

    Perlt, H.

    1980-01-01

    Scale breaking quark and gluon fragmentation functions obtained by solving numerically Altarelli-Parisi type equations are presented. Analytical parametrizations are given for the fragmentation of u and d quarks into pions. The calculated Q 2 dependent fragmentation functions are compared with experimental data. With these scale breaking fragmentation functions the average charged multiplicity is calculated in e + e - annihilation, which rises with energy more than logarithmically and is in good agreement with experiment. (author)

  4. The structural and functional differentiation of hair cells in a lizard’s basilar papilla suggests an operational principle of amniote cochleas

    Science.gov (United States)

    Chiappe, M. Eugenia; Kozlov, Andrei S.; Hudspeth, A. J.

    2007-01-01

    The hair cells in the mammalian cochlea are of two distinct types. Inner hair cells are responsible for transducing mechanical stimuli into electrical responses, which they forward to the brain through a copious afferent innervation. Outer hair cells, which are thought to mediate the active process that sensitizes and tunes the cochlea, possess a negligible afferent innervation. For every inner hair cell there are approximately three outer hair cells, so only a quarter of the hair cells directly deliver information to the central nervous system. Although this is a surprising feature for a sensory system, the occurrence of a similar innervation pattern in birds and crocodilians suggests that the arrangement has an adaptive value. Using a lizard with highly developed hearing, the tokay gecko, we demonstrate in the present study that the same principle operates in a third major group of terrestrial animals. We propose that the differentiation of hair cells into signaling and amplifying classes reflects incompatible strategies for the optimization of mechanoelectrical transduction and of an active process based on active hair-bundle motility. PMID:17978038

  5. A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships.

    Science.gov (United States)

    Pucci, Ferdinando; Venneri, Mary Anna; Biziato, Daniela; Nonis, Alessandro; Moi, Davide; Sica, Antonio; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele

    2009-07-23

    We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1(+)Cd11b(+) neutrophils/myeloid-derived suppressor cells, circulating "inflammatory" and "resident" monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction-based gene arrays. TEMs sharply differed from ECs and Gr1(+)Cd11b(+) cells but were highly related to TAMs. Nevertheless, several genes were differentially expressed between TEMs and TAMs, highlighting a TEM signature consistent with enhanced proangiogenic/tissue-remodeling activity and lower proinflammatory activity. We validated these findings in models of oncogenesis and transgenic mice expressing a microRNA-regulated Tie2-GFP reporter. Remarkably, resident monocytes and TEMs on one hand, and inflammatory monocytes and TAMs on the other hand, expressed coordinated gene expression profiles, suggesting that the 2 blood monocyte subsets are committed to distinct extravascular fates in the tumor microenvironment. We further showed that a prominent proportion of embryonic/fetal macrophages, which participate in tissue morphogenesis, expressed distinguishing TEM genes. It is tempting to speculate that Tie2(+) embryonic/fetal macrophages, resident blood monocytes, and tumor-infiltrating TEMs represent distinct developmental stages of a TEM lineage committed to execute physiologic proangiogenic and tissue-remodeling programs, which can be co-opted by tumors.

  6. Photoperiodic regulation of glycogen metabolism, glycolysis, and glutamine synthesis in tanycytes of the Siberian hamster suggests novel roles of tanycytes in hypothalamic function.

    Science.gov (United States)

    Nilaweera, Kanishka; Herwig, Annika; Bolborea, Matei; Campbell, Gill; Mayer, Claus D; Morgan, Peter J; Ebling, Francis J P; Barrett, Perry

    2011-11-01

    The objective of this study is to investigate the impact of photoperiod on the temporal and spatial expression of genes involved in glucose metabolism in the brain of the seasonal mammal Phodopus sungorus (Siberian hamster). In situ hybridization was performed on brain sections obtained from male hamsters held in long photoperiod (high body weight and developed testes) or short photoperiod (reduced body weight with testicular regression). This analysis revealed upregulation in expression of genes involved in glycogen and glucose metabolism in short photoperiod and localized to the tanycyte layer of the third ventricle. On the basis of these data and a previously identified photoperiod-dependent increase in activity of neighboring hypothalamic neurons, we hypothesized that the observed expression changes may reflect alteration in either metabolic fuel or precursor neurotransmitter supply to surrounding neurons. Gene expression analysis was performed for genes involved in lactate and glutamate transport. This analysis showed that the gene for the lactate transporter MCT2 and glutamate transporter GLAST was decreased in the tanycyte layer in short photoperiod. Expression of mRNA for glutamine synthetase, the final enzyme in the synthesis of the neuronal neurotransmitter precursor, glutamine, was also decreased in short photoperiod. These data suggest a role for tanycytes in modulating glutamate concentrations and neurotransmitter supply in the hypothalamic environment. Copyright © 2011 Wiley-Liss, Inc.

  7. 3-D thermal weight function method and multiple virtual crack extension technique for thermal shock problems

    International Nuclear Information System (INIS)

    Lu Yanlin; Zhou Xiao; Qu Jiadi; Dou Yikang; He Yinbiao

    2005-01-01

    An efficient scheme, 3-D thermal weight function (TWF) method, and a novel numerical technique, multiple virtual crack extension (MVCE) technique, were developed for determination of histories of transient stress intensity factor (SIF) distributions along 3-D crack fronts of a body subjected to thermal shock. The TWF is a universal function, which is dependent only on the crack configuration and body geometry. TWF is independent of time during thermal shock, so the whole history of transient SIF distributions along crack fronts can be directly calculated through integration of the products of TWF and transient temperatures and temperature gradients. The repeated determinations of the distributions of stresses (or displacements) fields for individual time instants are thus avoided in the TWF method. An expression of the basic equation for the 3-D universal weight function method for Mode I in an isotropic elastic body is derived. This equation can also be derived from Bueckner-Rice's 3-D WF formulations in the framework of transformation strain. It can be understood from this equation that the so-called thermal WF is in fact coincident with the mechanical WF except for some constants of elasticity. The details and formulations of the MVCE technique are given for elliptical cracks. The MVCE technique possesses several advantages. The specially selected linearly independent VCE modes can directly be used as shape functions for the interpolation of unknown SIFs. As a result, the coefficient matrix of the final system of equations in the MVCE method is a triple-diagonal matrix and the values of the coefficients on the main diagonal are large. The system of equations has good numerical properties. The number of linearly independent VCE modes that can be introduced in a problem is unlimited. Complex situations in which the SIFs vary dramatically along crack fronts can be numerically well simulated by the MVCE technique. An integrated system of programs for solving the

  8. Community functional responses to soil and climate at multiple spatial scales: when does intraspecific variation matter?

    Directory of Open Access Journals (Sweden)

    Andrew Siefert

    Full Text Available Despite increasing evidence of the importance of intraspecific trait variation in plant communities, its role in community trait responses to environmental variation, particularly along broad-scale climatic gradients, is poorly understood. We analyzed functional trait variation among early-successional herbaceous plant communities (old fields across a 1200-km latitudinal extent in eastern North America, focusing on four traits: vegetative height, leaf area, specific leaf area (SLA, and leaf dry matter content (LDMC. We determined the contributions of species turnover and intraspecific variation to between-site functional dissimilarity at multiple spatial scales and community trait responses to edaphic and climatic factors. Among-site variation in community mean trait values and community trait responses to the environment were generated by a combination of species turnover and intraspecific variation, with species turnover making a greater contribution for all traits. The relative importance of intraspecific variation decreased with increasing geographic and environmental distance between sites for SLA and leaf area. Intraspecific variation was most important for responses of vegetative height and responses to edaphic compared to climatic factors. Individual species displayed strong trait responses to environmental factors in many cases, but these responses were highly variable among species and did not usually scale up to the community level. These findings provide new insights into the role of intraspecific trait variation in plant communities and the factors controlling its relative importance. The contribution of intraspecific variation to community trait responses was greatest at fine spatial scales and along edaphic gradients, while species turnover dominated at broad spatial scales and along climatic gradients.

  9. Vibration control of uncertain multiple launch rocket system using radial basis function neural network

    Science.gov (United States)

    Li, Bo; Rui, Xiaoting

    2018-01-01

    Poor dispersion characteristics of rockets due to the vibration of Multiple Launch Rocket System (MLRS) have always restricted the MLRS development for several decades. Vibration control is a key technique to improve the dispersion characteristics of rockets. For a mechanical system such as MLRS, the major difficulty in designing an appropriate control strategy that can achieve the desired vibration control performance is to guarantee the robustness and stability of the control system under the occurrence of uncertainties and nonlinearities. To approach this problem, a computed torque controller integrated with a radial basis function neural network is proposed to achieve the high-precision vibration control for MLRS. In this paper, the vibration response of a computed torque controlled MLRS is described. The azimuth and elevation mechanisms of the MLRS are driven by permanent magnet synchronous motors and supposed to be rigid. First, the dynamic model of motor-mechanism coupling system is established using Lagrange method and field-oriented control theory. Then, in order to deal with the nonlinearities, a computed torque controller is designed to control the vibration of the MLRS when it is firing a salvo of rockets. Furthermore, to compensate for the lumped uncertainty due to parametric variations and un-modeled dynamics in the design of the computed torque controller, a radial basis function neural network estimator is developed to adapt the uncertainty based on Lyapunov stability theory. Finally, the simulated results demonstrate the effectiveness of the proposed control system and show that the proposed controller is robust with regard to the uncertainty.

  10. Cognitive function in multiple sclerosis improves with telerehabilitation: Results from a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Leigh E Charvet

    Full Text Available Cognitive impairment affects more than half of all individuals living with multiple sclerosis (MS. We hypothesized that training at home with an adaptive online cognitive training program would have greater cognitive benefit than ordinary computer games in cognitively-impaired adults with MS. This was a double-blind, randomized, active-placebo-controlled trial. Participants with MS were recruited through Stony Brook Medicine and randomly assigned to either the adaptive cognitive remediation (ACR program or active control of ordinary computer games for 60 hours over 12 weeks. Training was remotely-supervised and delivered through a study-provided laptop computer. A computer generated, blocked stratification table prepared by statistician provided the randomization schedule and condition was assigned by a study technician. The primary outcome, administered by study psychometrician, was measured by change in a neuropsychological composite measure from baseline to study end. An intent-to-treat analysis was employed and missing primary outcome values were imputed via Markov Chain Monte Carlo method. Participants in the ACR (n = 74 vs. active control (n = 61 training program had significantly greater improvement in the primary outcome of cognitive functioning (mean change in composite z score±SD: 0·25±0·45 vs. 0·09±0·37, p = 0·03, estimated difference = 0·16 with 95% CI: 0·02-0·30, despite greater training time in the active control condition (mean±SD:56·9 ± 34·6 vs. 37·7 ±23 ·8 hours played, p = 0·006. This study provides Class I evidence that adaptive, computer-based cognitive remediation accessed from home can improve cognitive functioning in MS. This telerehabilitation approach allowed for rapid recruitment and high compliance, and can be readily applied to other neurological conditions associated with cognitive dysfunction.Clinicaltrials.gov NCT02141386.

  11. Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.

    Science.gov (United States)

    Balsam, Leah; Saad, Chadi; Arsene, Camelia; Fogel, Joshua

    2017-01-01

    Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients. We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre-ASCT SBP and DBP. There was a significantly higher mean GFR at day of ASCT and 30 days post-ASCT and significantly lower mean GFR at 180 days post-ASCT as compared to pre-ASCT. White patients had similar patterns to the total group for SBP, DBP, and GFR except for SBP which was still significantly lower and GFR which was not significantly different at 180 days. African-American patients showed no significant reductions in the mean values of SBP and DBP and no significant increases for GFR in follow-up after day of ASCT. Furthermore, the mean value of GFR was significantly lower at 180 days post-ASCT. ASCT in MM patients had a positive impact on SBP and DBP and GFR but the impact was minimal for African-American patients. We recommend that clinicians consider closer follow-up of BP and kidney function and more intense therapy in African-Americans with MM. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

  12. On the multiple zeros of a real analytic function with applications to the averaging theory of differential equations

    Science.gov (United States)

    García, Isaac A.; Llibre, Jaume; Maza, Susanna

    2018-06-01

    In this work we consider real analytic functions , where , Ω is a bounded open subset of , is an interval containing the origin, are parameters, and ε is a small parameter. We study the branching of the zero-set of at multiple points when the parameter ε varies. We apply the obtained results to improve the classical averaging theory for computing T-periodic solutions of λ-families of analytic T-periodic ordinary differential equations defined on , using the displacement functions defined by these equations. We call the coefficients in the Taylor expansion of in powers of ε the averaged functions. The main contribution consists in analyzing the role that have the multiple zeros of the first non-zero averaged function. The outcome is that these multiple zeros can be of two different classes depending on whether the zeros belong or not to the analytic set defined by the real variety associated to the ideal generated by the averaged functions in the Noetheriang ring of all the real analytic functions at . We bound the maximum number of branches of isolated zeros that can bifurcate from each multiple zero z 0. Sometimes these bounds depend on the cardinalities of minimal bases of the former ideal. Several examples illustrate our results and they are compared with the classical theory, branching theory and also under the light of singularity theory of smooth maps. The examples range from polynomial vector fields to Abel differential equations and perturbed linear centers.

  13. Point spread function due to multiple scattering of light in the atmosphere

    International Nuclear Information System (INIS)

    Pękala, J.; Wilczyński, H.

    2013-01-01

    The atmospheric scattering of light has a significant influence on the results of optical observations of air showers. It causes attenuation of direct light from the shower, but also contributes a delayed signal to the observed light. The scattering of light therefore should be accounted for, both in simulations of air shower detection and reconstruction of observed events. In this work a Monte Carlo simulation of multiple scattering of light has been used to determine the contribution of the scattered light in observations of a point source of light. Results of the simulations and a parameterization of the angular distribution of the scattered light contribution to the observed signal (the point spread function) are presented. -- Author-Highlights: •Analysis of atmospheric scattering of light from an isotropic point source. •Different geometries and atmospheric conditions were investigated. •A parameterization of scattered light distribution has been developed. •The parameterization allows one to easily account for the light scattering in air. •The results will be useful in analyses of observations of extensive air shower

  14. Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma.

    Science.gov (United States)

    Iyoda, Tomonori; Yamasaki, Satoru; Hidaka, Michihiro; Kawano, Fumio; Abe, Yu; Suzuki, Kenshi; Kadowaki, Norimitsu; Shimizu, Kanako; Fujii, Shin-Ichiro

    2018-02-01

    NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56 dim CD16 + NK cells and DNAM-1 on CD56 bright CD16 - NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Hanford Site Welding Program Successfully Providing A Single Site Function For Use By Multiple Contractors

    International Nuclear Information System (INIS)

    Cannell, G.R.

    2009-01-01

    The Department of Energy, Richland Operations (DOE-RL) recently restructured its Hanford work scope, awarding two new contracts over the past several months for a total of three contracts to manage the sites cleanup efforts. DOE-RL met with key contractor personnel prior to and during contract transition to ensure site welding activities had appropriate oversight and maintained code compliance. The transition also provided an opportunity to establish a single site-wide function that would provide welding and materials engineering services to the Hanford site contractors: CH2M HILL Plateau Remediation Company (CHPRC); Mission Support Alliance (MSA); Washington River Protection Solutions (WRPS); and Washington Closure Hanford (WCH). Over the years, multiple and separate welding programs (amongst the several contractors) existed at the Hanford site leading to inefficiencies resulting from duplication of administrative efforts, maintenance of welding procedures, welder performance certifications, etc. The new, single program eliminates these inefficiencies. The new program, co-managed by two of the sites' new contractors, the CHPRC ('owner' of the program and responsible for construction welding services) and the MSA (provides maintenance welding services), provides more than just the traditional construction and maintenance welding services. Also provided, are welding engineering, specialty welding development/qualification for the closure of radioactive materials containers and materials evaluation/failure analysis. The following describes the new Hanford site welding program.

  16. Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection.

    Science.gov (United States)

    Parra-Cabrera, C; Samitier, J; Homs-Corbera, A

    2016-03-15

    We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10 ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The effect of executive function on stress, depression, anxiety, and quality of life in multiple sclerosis.

    Science.gov (United States)

    Grech, Lisa B; Kiropoulos, Litza A; Kirby, Katherine M; Butler, Ernest; Paine, Mark; Hester, Robert

    2015-01-01

    The experience of cognitive deficits and emotional dysfunction are prevalent in people with multiple sclerosis (PwMS), although research examining their interaction has provided inconsistent findings. The current study examined the ability of executive function to predict psychosocial adjustment in PwMS. One hundred and seven PwMS underwent cognitive assessment and completed measures of stress, depression, anxiety, and quality of life (QoL). There was limited support for a relationship. There was no relationship between objective cognitive tasks and state or trait anxiety, mental health QoL, overall QoL, or stress frequency. The only relationship with depression was found when the Beck Depression Inventory Fast-Screen was used, with a task of planning when the timing element was removed. A measure of error rates on a task of cognitive flexibility predicted physical health QoL, and severity, but not frequency, of stress was predicted by a task of working memory. The results of this study highlight the need for further research into the relationship between cognitive deficits and psychosocial adjustment because of the conflicting findings between studies and call for a common measurement framework for future investigation.

  18. Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging.

    Science.gov (United States)

    Genova, Helen M; Rajagopalan, Venkateswaran; Deluca, John; Das, Abhijit; Binder, Allison; Arjunan, Aparna; Chiaravalloti, Nancy; Wylie, Glenn

    2013-01-01

    The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS), looking specifically at the relationship between self-reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI) was used to examine where in the brain BOLD activity covaried with "state" fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI) was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS) completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a "fatigue-network" in MS.

  19. Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging.

    Directory of Open Access Journals (Sweden)

    Helen M Genova

    Full Text Available The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS, looking specifically at the relationship between self-reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI was used to examine where in the brain BOLD activity covaried with "state" fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a "fatigue-network" in MS.

  20. Simple index of functional connectivity at rest in Multiple Sclerosis fatigue.

    Science.gov (United States)

    Buyukturkoglu, Korhan; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Inglese, Matilde; Tecchio, Franca

    2017-05-01

    To investigate the EEG-derived functional connectivity at rest (FCR) patterns of fatigued Multiple Sclerosis (MS) patients in order to find good parameters for a future EEG-Neurofeedback intervention to reduce their fatigue symptoms. We evaluated FCR between hemispheric homologous areas, via spectral coherence between pairs of corresponding left and right bipolar derivations, in the Theta, Alpha and Beta bands. We estimated FCR in 18MS patients with different levels of fatigue and minimal clinical severity and in 11 age and gender matched healthy controls. We used correlation analysis to assess the relationship between the fatigue scores and the FCR values differing between fatigued MS patients and controls. Among FCR values differing between fatigued MS patients and controls, fatigue symptoms increased with higher Beta temporo-parietal FCR (p=0.00004). Also, positive correlations were found between the fatigue levels and the fronto-frontal FCR in Beta and Theta bands (p=0.0002 and p=0.001 respectively). We propose that a future EEG-Neurofeedback system against MS fatigue would train patients to decrease voluntarily the beta coherence between the homologous temporo-parietal areas. We extracted a feature for building an EEG-Neurofeedback system against fatigue in MS. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  1. Physical function and pain after surgical or conservative management of multiple rib fractures - a follow-up study.

    Science.gov (United States)

    Fagevik Olsén, Monika; Slobo, Margareta; Klarin, Lena; Caragounis, Eva-Corina; Pazooki, David; Granhed, Hans

    2016-10-28

    There is scarce knowledge of physical function and pain due to multiple rib fractures following trauma. The purpose of this follow-up was to assess respiratory and physical function, pain, range of movement and kinesiophobia in patients with multiple rib fractures who had undergone stabilizing surgery and compare with conservatively managed patients. A consecutive series of 31 patients with multiple rib fractures who had undergone stabilizing surgery were assessed >1 year after the trauma concerning respiratory and physical function, pain, range of movement in the shoulders and thorax, shoulder function and kinesiophobia. For comparison, 30 patients who were treated conservatively were evaluated with the same outcome measures. The results concerning pain, lung function, shoulder function and level of physical activity were similar in the two groups. The patients who had undergone surgery had a significantly larger range of motion in the thorax (p pain, better thoracic range of motion and physical function which would indicate that surgery is preferable. If operation technique could improve in the future with a less invasive approach, it would presumably decrease post-operative pain and the benefit of surgery would be greater than the morbidity of surgery. Patients undergoing surgery have a similar long-term recovery to those who are treated conservatively except for a better range of motion in the thorax and fewer limitations in physical function. Surgery seems to be beneficial for some patients, the question remains which patients. FoU i Sverige (R&D in Sweden), No 106121.

  2. A non-linear regression analysis program for describing electrophysiological data with multiple functions using Microsoft Excel.

    Science.gov (United States)

    Brown, Angus M

    2006-04-01

    The objective of this present study was to demonstrate a method for fitting complex electrophysiological data with multiple functions using the SOLVER add-in of the ubiquitous spreadsheet Microsoft Excel. SOLVER minimizes the difference between the sum of the squares of the data to be fit and the function(s) describing the data using an iterative generalized reduced gradient method. While it is a straightforward procedure to fit data with linear functions, and we have previously demonstrated a method of non-linear regression analysis of experimental data based upon a single function, it is more complex to fit data with multiple functions, usually requiring specialized expensive computer software. In this paper we describe an easily understood program for fitting experimentally acquired data, in this case the stimulus-evoked compound action potential from the mouse optic nerve, with multiple Gaussian functions. The program is flexible and can be applied to describe data with a wide variety of user-input functions.

  3. Multiple RNAs from the mouse carboxypeptidase M locus: functional RNAs or transcription noise?

    Directory of Open Access Journals (Sweden)

    Castilho Beatriz A

    2009-02-01

    Full Text Available Abstract Background A major effort of the scientific community has been to obtain complete pictures of the genomes of many organisms. This has been accomplished mainly by annotation of structural and functional elements in the genome sequence, a process that has been centred in the gene concept and, as a consequence, biased toward protein coding sequences. Recently, the explosion of transcriptome data generated and the discovery of many functional non-protein coding RNAs have painted a more detailed and complex scenario for the genome. Here we analyzed the mouse carboxypeptidase M locus in this broader perspective in order to define the mouse CPM gene structure and evaluate the existence of other transcripts from the same genomic region. Results Bioinformatic analysis of nucleotide sequences that map to the mouse CPM locus suggests that, in addition to the mouse CPM mRNA, it expresses at least 33 different transcripts, many of which seem to be non-coding RNAs. We randomly chose to evaluate experimentally four of these extra transcripts. They are expressed in a tissue specific manner, indicating that they are not artefacts or transcriptional noise. Furthermore, one of these four extra transcripts shows expression patterns that differed considerably from the other ones and from the mouse CPM gene, suggesting that there may be more than one transcriptional unit in this locus. In addition, we have confirmed the mouse CPM gene RefSeq sequence by rapid amplification of cDNA ends (RACE and directional cloning. Conclusion This study supports the recent view that the majority of the genome is transcribed and that many of the resulting transcripts seem to be non-coding RNAs from introns of genes or from independent transcriptional units. Although some of the information on the transcriptome of many organisms may actually be artefacts or transcriptional noise, we argue that it can be experimentally evaluated and used to find and define biological

  4. Snails and their trails: the multiple functions of trail-following in gastropods.

    Science.gov (United States)

    Ng, Terence P T; Saltin, Sara H; Davies, Mark S; Johannesson, Kerstin; Stafford, Richard; Williams, Gray A

    2013-08-01

    discrimination, including the mechanisms by which many snails determine the polarity of the trail, are yet to be experimentally determined. Given the multiple functions of trail-following we propose that future studies should adopt an integrated approach, taking into account the possibility of the simultaneous occurrence of many selectively advantageous roles of trail-following behaviour in gastropods. We also believe that future opportunities to link phenotypic and genotypic traits will make possible a new generation of research projects in which gastropod trail-following, its multitude of functions and evolutionary trade-offs can be further elucidated. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  5. Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix

    Directory of Open Access Journals (Sweden)

    Kuo Lillian S

    2012-05-01

    Full Text Available Abstract Background HIV-1 Nef is a multifunctional protein required for full pathogenicity of the virus. As Nef has no known enzymatic activity, it necessarily functions through protein-protein interaction interfaces. A critical Nef protein interaction interface is centered on its polyproline segment (P69VRPQVPLRP78 which contains the helical SH3 domain binding protein motif, PXXPXR. We hypothesized that any Nef-SH3 domain interactions would be lost upon mutation of the prolines or arginine of PXXPXR. Further, mutation of the non-motif “X” residues, (Q73, V74, and L75 would give altered patterns of inhibition for different Nef/SH3 domain protein interactions. Results We found that mutations of either of the prolines or the arginine of PXXPXR are defective for Nef-Hck binding, Nef/activated PAK2 complex formation and enhancement of virion infectivity (EVI. Mutation of the non-motif “X” residues (Q, V and L gave similar patterns of inhibition for Nef/activated PAK2 complex formation and EVI which were distinct from the pattern for Hck binding. These results implicate an SH3 domain containing protein other than Hck for Nef/activated PAK2 complex formation and EVI. We have also mutated Nef residues at the N-and C-terminal ends of the polyproline segment to explore interactions outside of PXXPXR. We discovered a new locus GFP/F (G67, F68, P69 and F90 that is required for Nef/activated PAK2 complex formation and EVI. MHC Class I (MHCI downregulation was only partially inhibited by mutating the PXXPXR motif residues, but was fully inhibited by mutating the C-terminal P78. Further, we observed that MHCI downregulation strictly requires G67 and F68. Our mutational analysis confirms the recently reported structure of the complex between Nef, AP-1 μ1 and the cytoplasmic tail of MHCI, but does not support involvement of an SH3 domain protein in MHCI downregulation. Conclusion Nef has evolved to be dependent on interactions with multiple SH3 domain

  6. Impacts of multiple stressors on ecosystem function: Leaf decomposition in constructed urban wetlands

    International Nuclear Information System (INIS)

    Mackintosh, Teresa J.; Davis, Jenny A.; Thompson, Ross M.

    2016-01-01

    The impact of stormwater on stream biota is well documented, but less is known about the impacts on ecosystem processes, such as the breakdown of organic matter. This study sought to establish whether the degree of urbanisation affected rates of leaf-litter breakdown within constructed wetlands. A litter bag method was used to ascertain rate of decomposition along a gradient of urbanisation (total imperviousness, TI), in constructed wetlands in western and south-eastern Melbourne. A significant positive relationship between TI and breakdown rate was found in the south-eastern wetlands. The significant reduction in rate of invertebrate-mediated breakdown with increasing concentration of certain metals was consistent with other studies. However, overall there was an increase in rate of breakdown. Studies have shown that the effects of heavy metals can be negated if nutrient levels are high. Our results suggest that other parameters besides exposure to contaminants are likely to affect leaf litter breakdown. - Highlights: • There have been few studies on the effect of urbanisation on ecosystem function. • Rate of leaf litter breakdown increased moving along a gradient of urbanisation. • There was a reduction in invertebrate mediated breakdown with certain metals. • Results suggest other parameters besides contaminants affect leaf litter breakdown. - Certain heavy metals led to a decrease in leaf litter breakdown; however overall, there was a positive relationship between breakdown and increasing urbanisation.

  7. Method to map one-dimensional electronic wave function by using multiple Brillouin zone angle resolved photoemission

    Directory of Open Access Journals (Sweden)

    Dong-Wook Lee

    2010-10-01

    Full Text Available Angle resolved photoemission spectroscopy (ARPES is a powerful tool to investigate electronic structures in solids and has been widely used in studying various materials. The electronic structure information by ARPES is obtained in the momentum space. However, in the case of one-dimensional system, we here show that we extract the real space information from ARPES data taken over multiple Brillouin zones (BZs. Intensities in the multiple BZs are proportional to the photoemission matrix element which contains information on the coefficient of the Bloch wave function. It is shown that the Bloch wave function coefficients can be extracted from ARPES data, which allows us to construct the real space wave function. As a test, we use ARPES data from proto-typical one-dimensional system SrCuO2 and construct the real space wave function.

  8. Optimizing Placement of Weather Stations: Exploring Objective Functions of Meaningful Combinations of Multiple Weather Variables

    Science.gov (United States)

    Snyder, A.; Dietterich, T.; Selker, J. S.

    2017-12-01

    Many regions of the world lack ground-based weather data due to inadequate or unreliable weather station networks. For example, most countries in Sub-Saharan Africa have unreliable, sparse networks of weather stations. The absence of these data can have consequences on weather forecasting, prediction of severe weather events, agricultural planning, and climate change monitoring. The Trans-African Hydro-Meteorological Observatory (TAHMO.org) project seeks to address these problems by deploying and operating a large network of weather stations throughout Sub-Saharan Africa. To design the TAHMO network, we must determine where to place weather stations within each country. We should consider how we can create accurate spatio-temporal maps of weather data and how to balance the desired accuracy of each weather variable of interest (precipitation, temperature, relative humidity, etc.). We can express this problem as a joint optimization of multiple weather variables, given a fixed number of weather stations. We use reanalysis data as the best representation of the "true" weather patterns that occur in the region of interest. For each possible combination of sites, we interpolate the reanalysis data between selected locations and calculate the mean average error between the reanalysis ("true") data and the interpolated data. In order to formulate our multi-variate optimization problem, we explore different methods of weighting each weather variable in our objective function. These methods include systematic variation of weights to determine which weather variables have the strongest influence on the network design, as well as combinations targeted for specific purposes. For example, we can use computed evapotranspiration as a metric that combines many weather variables in a way that is meaningful for agricultural and hydrological applications. We compare the errors of the weather station networks produced by each optimization problem formulation. We also compare these

  9. Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

    Science.gov (United States)

    Zeydan, Burcu; Lowe, Val J; Schwarz, Christopher G; Przybelski, Scott A; Tosakulwong, Nirubol; Zuk, Samantha M; Senjem, Matthew L; Gunter, Jeffrey L; Roberts, Rosebud O; Mielke, Michelle M; Benarroch, Eduardo E; Rodriguez, Moses; Machulda, Mary M; Lesnick, Timothy G; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal; Kantarci, Orhun H

    2018-05-01

    There is growing interest in white matter (WM) imaging with positron emission tomography (PET). We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.

  10. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    International Nuclear Information System (INIS)

    Erdas, Enrico; Mariotti, Stefano; Pomata, Mariano; Aste, Nicola; Pilloni, Luca; Nicolosi, Angelo; Licheri, Sergio; Cappai, Antonello; Mastinu, Marco; Cetani, Filomena; Pardi, Elena

    2012-01-01

    Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99m Tc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

  11. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Directory of Open Access Journals (Sweden)

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  12. Molecular cloning and functional characterization of multiple NADPH-cytochrome P450 reductases from Andrographis paniculata.

    Science.gov (United States)

    Lin, Huixin; Wang, Jian; Qi, Mengdie; Guo, Juan; Rong, Qixian; Tang, Jinfu; Wu, Yisheng; Ma, Xiaojing; Huang, Luqi

    2017-09-01

    Andrographis paniculata (Burm.f.) Wall. ex Nees is widely used as medicinal herb in Southern and Southeastern Asia and andrographolide is its main medicinal constituent. Based on the structure of andrographolide, it has been proposed that cytochrome P450 enzymes play vital roles on its biosynthesis. NADPH:cytochrome P450 reductase (CPR) is the most important redox partner of multiple P450s. In this study, three CPRs were identified in the genomic data of A. paniculata (namely ApCPR1, ApCPR2, and ApCPR3), and their coding regions were cloned. They varied from 62% to 70% identities to each other at the amino acid sequence level. ApCPR1 belongs to Class I of dicotyledonous CPR while both ApCPR2 and ApCPR3 are grouped to Class II. The recombinant enzymes ApCPR1 and ApCPR2 reduced cytochrome c and ferricyanide in an NADPH-dependent manner. In yeast, they supported the activity of CYP76AH1, a ferruginol-forming enzyme. However, ApCPR3 did not show any enzymatic activities either in vitro or in vivo. Quantitative real-time PCR analysis showed that both ApCPR1 and ApCPR2 expressed in all tissues examined, but ApCPR2 showed higher expression in leaves. Expression of ApCPR2 was inducible by MeJA and its pattern matched with andrographolide accumulation. Present investigation suggested ApCPR2 involves in the biosynthesis of secondary metabolites including andrographolide. Copyright © 2017. Published by Elsevier B.V.

  13. Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

    Directory of Open Access Journals (Sweden)

    Samuel Neal Lockhart

    2012-03-01

    Full Text Available Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH and fractional anisotropy (FA obtained from diffusion tensor imaging, differ with aging and cerebrovascular disease and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals.

  14. Novel functional polymorphism in IGF-1 gene associated with multiple sclerosis: A new insight to MS.

    Science.gov (United States)

    Shahbazi, Majid; Abdolmohammadi, Reza; Ebadi, Hamid; Farazmandfar, Touraj

    2017-04-01

    Interactions between several genes and environment may play a role in susceptibility to multiple sclerosis (MS). The IGF-1 plays a key role in proliferation, maintenance and survival of nerve cells. Therefore, we hypothesized that IGF-1 may be a target for prediction and control MS. We aimed to analysis IGF-1 gene promoter sequence, to investigate the effect of the single nucleotide variants on IGF-1 expression and its association with MS. We enrolled 339 MS patients and 431 healthy controls. A specific region in IGF-1 gene promoter was investigated by SSCP analysis. All samples were genotyped by SSP-PCR. In-vitro and in-vivo IGF-1 production was measured by ELISA assay. IGF-1 expression in PBMCs was measured using real-time PCR. We identified a T to C single nucleotide substitution at position -1089 and a C to T at position -383 from transcription start site in the IGF-1 gene promoter. There was a significant association between MS and genotypes IGF-1(-383) C/T (p=0.001) and IGF-1(-383) C/C (pMS (p=0.001). In-vitro and in-vivo IGF-1 level showed that IGF-1 production in samples with genotype IGF-1(-383) C/C significantly was less than T/T (p=0.004) but not T/C (p=0.220). According to IGF-1 roles in CNS and our results, this study suggests that low IGF-1 level may be associated with susceptibility to MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

    Directory of Open Access Journals (Sweden)

    Junhong Gui

    2010-06-01

    Full Text Available To identify molecular mechanisms underlying SCN5A-related sick sinus syndrome (SSS, a rare type of SSS, in parallel experiments we elucidated the electrophysiological properties and the cell surface localization of thirteen human Na(v1.5 (hNa(v1.5 mutant channels previously linked to this disease.Mutant hNa(v1.5 channels expressed by HEK293 cells and Xenopus oocytes were investigated by whole-cell patch clamp and two-microelectrode voltage clamp, respectively. HEK293 cell surface biotinylation experiments quantified the fraction of correctly targeted channel proteins. Our data suggested three distinct mutant channel subtypes: Group 1 mutants (L212P, P1298L, DelF1617, R1632H gave peak current densities and cell surface targeting indistinguishable from wild-type hNa(v1.5. Loss-of-function of these mutants resulted from altered channel kinetics, including a negative shift of steady-state inactivation and a reduced voltage dependency of open-state inactivation. Group 2 mutants (E161K, T220I, D1275N gave significantly reduced whole-cell currents due to impaired cell surface localization (D1275N, altered channel properties at unchanged cell surface localization (T220I, or a combination of both (E161K. Group 3 mutant channels were non-functional, due to an almost complete lack of protein at the plasma membrane (T187I, W1421X, K1578fs/52, R1623X or a probable gating/permeation defect with normal surface localisation (R878C, G1408R.This study indicates that multiple molecular mechanisms, including gating abnormalities, trafficking defects, or a combination of both, are responsible for SCN5A-related familial SSS.

  16. Exercise, Diet, and Stress Management as Mediators between Functional Disability and Health-Related Quality of Life in Multiple Sclerosis

    Science.gov (United States)

    Sung, Connie; Chiu, Chung-Yi; Lee, Eun-Jeong; Bezyak, Jill; Chan, Fong; Muller, Veronica

    2013-01-01

    The main objective of this study was to examine the mediational and moderational effect of exercise, diet, and stress management on the relationship between functional disability and health-related quality of life. Quantitative descriptive research design using multiple regression and correlation techniques was used. Participants were 215…

  17. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

    Science.gov (United States)

    Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

    2017-02-01

    Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

  18. Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection.

    Science.gov (United States)

    Pène, Véronique; Li, Qisheng; Sodroski, Catherine; Hsu, Ching-Sheng; Liang, T Jake

    2015-05-01

    The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3' untranslated region (UTR), leading to the activation of IKK-α and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3'UTR interacts with DDX3X and IKK-α, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-α, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-α, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3'UTR, activating IKK-α and

  19. Suggestive Objects at Work

    DEFF Research Database (Denmark)

    Ratner, Helene Gad

    2009-01-01

    In Western secular societies, spiritual life is no longer limited to classical religious institutions but can also be found at workplace organizations. While spirituality is conventionally understood as a subjective and internal process, this paper proposes the concept of ‘suggestive objects......’, constructed by combining insights from Gabriel Tarde's sociology with Bruno Latour's actor-network theory, to theorize the material dimension of organizational spirituality. The sacred in organizations arises not from the internalization of collective values but through the establishment of material...... scaffolding. This has deep implications for our understanding of the sacred, including a better appreciation of the way that suggestive objects make the sacred durable, the way they organize it....

  20. Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals.

    Science.gov (United States)

    Cohen, D A; Stotelmyer, N L; Kaplan, A M

    1985-04-01

    The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.

  1. Multiple determinants of transfer of evaluative function after conditioning with free-operant schedules of reinforcement.

    Science.gov (United States)

    Dack, Charlotte; Reed, Phil; McHugh, Louise

    2010-11-01

    The aim of the four present experiments was to explore how different schedules of reinforcement influence schedule-induced behavior, their impact on evaluative ratings given to conditioned stimuli associated with each schedule through evaluative conditioning, and the transfer of these evaluations through derived stimulus networks. Experiment 1 compared two contrasting response reinforcement rules (variable ratio [VR], variable interval [VI]). Experiment 2 varied the response to reinforcement rule between two schedules but equated the outcome to response rate (differential reinforcement of high rate [DRH] vs. VR). Experiment 3 compared molar and molecular aspects of contingencies of reinforcement (tandem VIVR vs. tandem VRVI). Finally, Experiment 4 employed schedules that induced low rates of responding to determine whether, under these circumstances, responses were more sensitive to the molecular aspects of a schedule (differential reinforcement of low rate [DRL] vs. VI). The findings suggest that the transfer of evaluative functions is determined mainly by differences in response rate between the schedules and the molar aspects of the schedules. However, when neither schedule was based on a strong response reinforcement rule, the transfer of evaluative judgments came under the control of the molecular aspects of the schedule.

  2. Lidar inelastic multiple-scattering parameters of cirrus particle ensembles determined with geometrical-optics crystal phase functions.

    Science.gov (United States)

    Reichardt, J; Hess, M; Macke, A

    2000-04-20

    Multiple-scattering correction factors for cirrus particle extinction coefficients measured with Raman and high spectral resolution lidars are calculated with a radiative-transfer model. Cirrus particle-ensemble phase functions are computed from single-crystal phase functions derived in a geometrical-optics approximation. Seven crystal types are considered. In cirrus clouds with height-independent particle extinction coefficients the general pattern of the multiple-scattering parameters has a steep onset at cloud base with values of 0.5-0.7 followed by a gradual and monotonic decrease to 0.1-0.2 at cloud top. The larger the scattering particles are, the more gradual is the rate of decrease. Multiple-scattering parameters of complex crystals and of imperfect hexagonal columns and plates can be well approximated by those of projected-area equivalent ice spheres, whereas perfect hexagonal crystals show values as much as 70% higher than those of spheres. The dependencies of the multiple-scattering parameters on cirrus particle spectrum, base height, and geometric depth and on the lidar parameters laser wavelength and receiver field of view, are discussed, and a set of multiple-scattering parameter profiles for the correction of extinction measurements in homogeneous cirrus is provided.

  3. The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

    Science.gov (United States)

    Kuiper, Gerhardus J A J M; Houben, Rik; Wetzels, Rick J H; Verhezen, Paul W M; Oerle, Rene van; Ten Cate, Hugo; Henskens, Yvonne M C; Lancé, Marcus D

    2017-11-01

    Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r 2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r 2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

  4. The importance of biodiversity and dominance for multiple ecosystem functions in a human-modified tropical landscape

    NARCIS (Netherlands)

    Lohbeck, M.W.M.; Bongers, F.; Martinez-Ramos, M.; Poorter, L.

    2016-01-01

    Many studies suggest that biodiversity may be particularly important for ecosystem multifunctionality, because different species with different traits can contribute to different functions. Support, however, comes mostly from experimental studies conducted at small spatial scales in low-diversity

  5. Comparison of multiple linear regression and artificial neural network in developing the objective functions of the orthopaedic screws.

    Science.gov (United States)

    Hsu, Ching-Chi; Lin, Jinn; Chao, Ching-Kong

    2011-12-01

    Optimizing the orthopaedic screws can greatly improve their biomechanical performances. However, a methodical design optimization approach requires a long time to search the best design. Thus, the surrogate objective functions of the orthopaedic screws should be accurately developed. To our knowledge, there is no study to evaluate the strengths and limitations of the surrogate methods in developing the objective functions of the orthopaedic screws. Three-dimensional finite element models for both the tibial locking screws and the spinal pedicle screws were constructed and analyzed. Then, the learning data were prepared according to the arrangement of the Taguchi orthogonal array, and the verification data were selected with use of a randomized selection. Finally, the surrogate objective functions were developed by using either the multiple linear regression or the artificial neural network. The applicability and accuracy of those surrogate methods were evaluated and discussed. The multiple linear regression method could successfully construct the objective function of the tibial locking screws, but it failed to develop the objective function of the spinal pedicle screws. The artificial neural network method showed a greater capacity of prediction in developing the objective functions for the tibial locking screws and the spinal pedicle screws than the multiple linear regression method. The artificial neural network method may be a useful option for developing the objective functions of the orthopaedic screws with a greater structural complexity. The surrogate objective functions of the orthopaedic screws could effectively decrease the time and effort required for the design optimization process. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Effect of halloysite nanotubes on the structure and function of important multiple blood components

    International Nuclear Information System (INIS)

    Wu, Keke; Feng, Ru; Jiao, Yanpeng; Zhou, Changren

    2017-01-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV–vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. - Highlights: • Comprehensive study of blood compatibility halloysite nanotubes (HNTs) is processed. • We examine and analyze the effect of HNTs on conformation changes of three plasma proteins. • We prove HNTs can affect blood components at high content but little at low content. • We prove HNTs could be used as biomaterials

  7. Effect of halloysite nanotubes on the structure and function of important multiple blood components.

    Science.gov (United States)

    Wu, Keke; Feng, Ru; Jiao, Yanpeng; Zhou, Changren

    2017-06-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV-vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effect of halloysite nanotubes on the structure and function of important multiple blood components

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Keke; Feng, Ru; Jiao, Yanpeng, E-mail: tjiaoyp@jnu.edu.cn; Zhou, Changren

    2017-06-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV–vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. - Highlights: • Comprehensive study of blood compatibility halloysite nanotubes (HNTs) is processed. • We examine and analyze the effect of HNTs on conformation changes of three plasma proteins. • We prove HNTs can affect blood components at high content but little at low content. • We prove HNTs could be used as biomaterials

  9. Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

    Science.gov (United States)

    Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

    2013-11-01

    The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

  10. High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing's syndrome suggests that the paradigm for diagnosis and exclusion of Cushing's syndrome requires multiple testing.

    Science.gov (United States)

    Friedman, T C; Ghods, D E; Shahinian, H K; Zachery, L; Shayesteh, N; Seasholtz, S; Zuckerbraun, E; Lee, M L; McCutcheon, I E

    2010-11-01

    Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92% for 23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

    Science.gov (United States)

    Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn

    2005-07-01

    We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

  12. Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory

    Science.gov (United States)

    Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn

    2005-01-01

    We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory. PMID

  13. Monitoring the Effect of Facilitation Physiotherapy in Multiple Sclerosis using Functional Magnetic Resonance Imaging

    Czech Academy of Sciences Publication Activity Database

    Procházková, M.; Řasová, K.; Tintěra, J.; Martinková, Patrícia; Procházka, A.

    2014-01-01

    Roč. 20, č. 7 (2014), s. 1003-1004 ISSN 1352-4585. [RIMS 2014. Annual Conference on Rehabilitation in Multiple Sclerosis /19./. 06.06.2014-07.06.2014, Brighton] Institutional support: RVO:67985807 Subject RIV: BB - Applied Statistics, Operational Research

  14. Visual impairments in people with severe and profound multiple disabilities: An inventory of visual functioning

    NARCIS (Netherlands)

    van den Broek, E.G.C.; Janssen, C.G.C.; van Ramshorst, T.; Deen, L.

    2006-01-01

    Background: The prevalence of visual impairments in people with severe and profound multiple disabilities (SPMD) is the subject of considerable debate and is difficult to assess. Methods: In a typical Dutch care organization, all clients with SPMD (n = 76) participated in the study and specific

  15. A Method of Calculating Functional Independence Measure at Discharge from Functional Independence Measure Effectiveness Predicted by Multiple Regression Analysis Has a High Degree of Predictive Accuracy.

    Science.gov (United States)

    Tokunaga, Makoto; Watanabe, Susumu; Sonoda, Shigeru

    2017-09-01

    Multiple linear regression analysis is often used to predict the outcome of stroke rehabilitation. However, the predictive accuracy may not be satisfactory. The objective of this study was to elucidate the predictive accuracy of a method of calculating motor Functional Independence Measure (mFIM) at discharge from mFIM effectiveness predicted by multiple regression analysis. The subjects were 505 patients with stroke who were hospitalized in a convalescent rehabilitation hospital. The formula "mFIM at discharge = mFIM effectiveness × (91 points - mFIM at admission) + mFIM at admission" was used. By including the predicted mFIM effectiveness obtained through multiple regression analysis in this formula, we obtained the predicted mFIM at discharge (A). We also used multiple regression analysis to directly predict mFIM at discharge (B). The correlation between the predicted and the measured values of mFIM at discharge was compared between A and B. The correlation coefficients were .916 for A and .878 for B. Calculating mFIM at discharge from mFIM effectiveness predicted by multiple regression analysis had a higher degree of predictive accuracy of mFIM at discharge than that directly predicted. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Existence, Multiplicity, and Stability of Positive Solutions of a Predator-Prey Model with Dinosaur Functional Response

    Directory of Open Access Journals (Sweden)

    Xiaozhou Feng

    2017-01-01

    Full Text Available We investigate the property of positive solutions of a predator-prey model with Dinosaur functional response under Dirichlet boundary conditions. Firstly, using the comparison principle and fixed point index theory, the sufficient conditions and necessary conditions on coexistence of positive solutions of a predator-prey model with Dinosaur functional response are established. Secondly, by virtue of bifurcation theory, perturbation theory of eigenvalues, and the fixed point index theory, we establish the bifurcation of positive solutions of the model and obtain the stability and multiplicity of the positive solution under certain conditions. Furthermore, the local uniqueness result is studied when b and d are small enough. Finally, we investigate the multiplicity, uniqueness, and stability of positive solutions when k>0 is sufficiently large.

  17. ADNP-CSMA Random Multiple Access protocol application with the function of monitoring in Ad Hoc network

    Directory of Open Access Journals (Sweden)

    Zhan Gang

    2016-01-01

    Full Text Available In Ad Hoc networks,the net work of mobile nodes exchange information with their wireless transceiver equipment,the network throughput is in increased,compared to other such multiple hops network.Moreover along with the rapid development of modern information,communication business also will be increase.However,the access and adaptive of previous CSMA protocol are insufficient.According to these properties,this paper presents a kind of adaptive dual clock with monitoring function P-CSMA random multiple access protocol(ADNP-CSMA,and discusses two kinds of P-CSMA.ACK with monitoring function is introduced to maintain the stability of the whole system,and the introduction of dual clock mechanism reduces the channel of idle period.It calculate the system throughput expression through the method of average period,and the simulation results show that the system is constant in the case of high load throughput.

  18. Continuity in Λ-variation of functions of several variables and convergence of multiple Fourier series

    International Nuclear Information System (INIS)

    Bakhvalov, A N

    2002-01-01

    The behaviour of rectangular partial sums of the Fourier series of functions of several variables having bounded Λ-variation is considered. It is proved that if a continuous function is also continuous in harmonic variation, then its Fourier series uniformly converges in the sense of Pringsheim. On the other hand, it is demonstrated that in dimensions greater than 2 there always exists a continuous function of bounded harmonic variation with Fourier series divergent over cubes at the origin

  19. Structured association analysis leads to insight into Saccharomyces cerevisiae gene regulation by finding multiple contributing eQTL hotspots associated with functional gene modules.

    Science.gov (United States)

    Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P

    2013-03-21

    Association analysis using genome-wide expression quantitative trait locus (eQTL) data investigates the effect that genetic variation has on cellular pathways and leads to the discovery of candidate regulators. Traditional analysis of eQTL data via pairwise statistical significance tests or linear regression does not leverage the availability of the structural information of the transcriptome, such as presence of gene networks that reveal correlation and potentially regulatory relationships among the study genes. We employ a new eQTL mapping algorithm, GFlasso, which we have previously developed for sparse structured regression, to reanalyze a genome-wide yeast dataset. GFlasso fully takes into account the dependencies among expression traits to suppress false positives and to enhance the signal/noise ratio. Thus, GFlasso leverages the gene-interaction network to discover the pleiotropic effects of genetic loci that perturb the expression level of multiple (rather than individual) genes, which enables us to gain more power in detecting previously neglected signals that are marginally weak but pleiotropically significant. While eQTL hotspots in yeast have been reported previously as genomic regions controlling multiple genes, our analysis reveals additional novel eQTL hotspots and, more interestingly, uncovers groups of multiple contributing eQTL hotspots that affect the expression level of functional gene modules. To our knowledge, our study is the first to report this type of gene regulation stemming from multiple eQTL hotspots. Additionally, we report the results from in-depth bioinformatics analysis for three groups of these eQTL hotspots: ribosome biogenesis, telomere silencing, and retrotransposon biology. We suggest candidate regulators for the functional gene modules that map to each group of hotspots. Not only do we find that many of these candidate regulators contain mutations in the promoter and coding regions of the genes, in the case of the Ribi group

  20. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Science.gov (United States)

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Exercise therapy in multiple sclerosis and its effects on function and the brain

    DEFF Research Database (Denmark)

    Dalgas, Ulrik

    2017-01-01

    to clinically relevant improvements in physical function, but should be considered an adjunct to specific task-based training. Exercise has also shown positive effects on the brain, including improvements in brain volume and cognition. In summary, exercise therapy is a safe and potent nonpharmacological...... intervention in MS, with beneficial effects on both functional capacity and the brain....

  2. A Generalized Logistic Regression Procedure to Detect Differential Item Functioning among Multiple Groups

    Science.gov (United States)

    Magis, David; Raiche, Gilles; Beland, Sebastien; Gerard, Paul

    2011-01-01

    We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence…

  3. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  4. [The influence of high-tone power therapy on the functional status of patients with multiple sclerosis].

    Science.gov (United States)

    Kubsik, Anna; Klimkiewicz, Paulina; Klimkiewicz, Robert; Jankowska, Katarzyna; Jankowska, Agnieszka; Woldańska-Okońska, Marta

    2014-07-01

    Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, which is characterized by diverse symptomatology. Most often affects people at a young age gradually leading to their disability. Looking for new therapies to alleviate neurological deficits caused by the disease. One of the alternative methods of therapy is high - tone power therapy. The article is a comparison of high-tone power therapy and kinesis in improving patients with multiple sclerosis. The aim of this study was to evaluate the effectiveness of high-tone power therapy and exercises in kinesis on the functional status of patients with multiple sclerosis. The study involved 20 patients with multiple sclerosis, both sexes, treated at the Department of Rehabilitation and Physical Medicine in Lodz. Patients were randomly divided into two groups studied. In group high-tone power therapy applied for 60 minutes, while in group II were used exercises for kinesis. Treatment time for both groups of patients was 15 days. To assess the functional status scale was used: Expanded Disability Status Scale of Kurtzke (EDSS), as well as by Barthel ADL Index. Assessment of quality of life were made using MSQOL Questionnaire-54. For the evaluation of gait and balance using Tinetti scale, and pain VAS rated, and Laitinen. Changes in muscle tone was assessed on the basis of the Ashworth scale. Both group I and II improved on scales conducted before and after therapy. In group I, in which the applied high-tone power therapy, reported statistically significant results in 9 out of 10 tested parameters, while in group II, which was used in the exercises in kinesis an improvement in 6 out of 10 tested parameters. Correlating the results of both the test groups in relation to each other did not show statistically significant differences. High-Tone Power Therapy beneficial effect on the functional status of patients with multiple sclerosis. Obtaining results in terms of number of tested

  5. Multiple Past Concussions in High School Football Players: Are There Differences in Cognitive Functioning and Symptom Reporting?

    Science.gov (United States)

    Brooks, Brian L; Mannix, Rebekah; Maxwell, Bruce; Zafonte, Ross; Berkner, Paul D; Iverson, Grant L

    2016-12-01

    There is increasing concern about the possible long-term effects of multiple concussions, particularly on the developing adolescent brain. Whether the effect of multiple concussions is detectable in high school football players has not been well studied, although the public health implications are great in this population. To determine if there are measureable differences in cognitive functioning or symptom reporting in high school football players with a history of multiple concussions. Cross-sectional study; Level of evidence, 3. Participants included 5232 male adolescent football players (mean [±SD] age, 15.5 ± 1.2 years) who completed baseline testing between 2009 and 2014. On the basis of injury history, athletes were grouped into 0 (n = 4183), 1 (n = 733), 2 (n = 216), 3 (n = 67), or ≥4 (n = 33) prior concussions. Cognitive functioning was measured by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery, and symptom ratings were obtained from the Post-Concussion Symptom Scale. There were no statistically significant differences between groups (based on the number of reported concussions) regarding cognitive functioning. Athletes with ≥3 prior concussions reported more symptoms than did athletes with 0 or 1 prior injury. In multivariate analyses, concussion history was independently related to symptom reporting but less so than developmental problems (eg, attention or learning problems) or other health problems (eg, past treatment for psychiatric problems, headaches, or migraines). In the largest study to date, high school football players with multiple past concussions performed the same on cognitive testing as those with no prior concussions. Concussion history was one of several factors that were independently related to symptom reporting. © 2016 The Author(s).

  6. GESTATIONAL ATRAZINE EXPOSURE IN THE RAT: EFFECTS ON MAMMARY GLAND DEVELOPMENT AND FUNCTION IN MULTIPLE GENERATIONS

    Science.gov (United States)

    The chlorotriazine herbicides currently represent the most heavily used of all agricultural pesticides, with atrazine being the most common of these chemicals. Rodent toxicology studies indicate that atrazine can disrupt endocrine function and among its effects is an increased in...

  7. Multiple joint muscle function with ageing: the force-velocity and power-velocity relationships in young and older men.

    Science.gov (United States)

    Allison, Sarah J; Brooke-Wavell, Katherine; Folland, Jonathan P

    2013-05-01

    Whilst extensive research has detailed the loss of muscle strength with ageing for isolated single joint actions, there has been little attention to power production during more functionally relevant multiple joint movements. The extent to which force or velocity are responsible for the loss in power with ageing is also equivocal. The aim of this study was to evaluate the contribution of force and velocity to the differences in power with age by comparing the force-velocity and power-velocity relationships in young and older men during a multiple joint leg press movement. Twenty-one older men (66 ± 3 years) and twenty-three young men (24 ± 2 years) completed a series of isometric (maximum and explosive) and dynamic contractions on a leg press dynamometer instrumented to record force and displacement. The force-velocity relationship was lower for the older men as reflected by their 19 % lower maximum isometric strength (p decrement in force was greater and therefore the major explanation for the attenuation of power during a functionally relevant multiple joint movement.

  8. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

  9. Dimensional feature weighting utilizing multiple kernel learning for single-channel talker location discrimination using the acoustic transfer function.

    Science.gov (United States)

    Takashima, Ryoichi; Takiguchi, Tetsuya; Ariki, Yasuo

    2013-02-01

    This paper presents a method for discriminating the location of the sound source (talker) using only a single microphone. In a previous work, the single-channel approach for discriminating the location of the sound source was discussed, where the acoustic transfer function from a user's position is estimated by using a hidden Markov model of clean speech in the cepstral domain. In this paper, each cepstral dimension of the acoustic transfer function is newly weighted, in order to obtain the cepstral dimensions having information that is useful for classifying the user's position. Then, this paper proposes a feature-weighting method for the cepstral parameter using multiple kernel learning, defining the base kernels for each cepstral dimension of the acoustic transfer function. The user's position is trained and classified by support vector machine. The effectiveness of this method has been confirmed by sound source (talker) localization experiments performed in different room environments.

  10. Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

    Science.gov (United States)

    Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

    2015-03-01

    There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

  11. Minimising farm crop protection pressure supported by the multiple functionalities of the DISCUSS indicator set.

    Science.gov (United States)

    Wustenberghs, Hilde; Fevery, Davina; Lauwers, Ludwig; Marchand, Fleur; Spanoghe, Pieter

    2018-03-15

    Sustainable crop protection (SCP) has many facets. Farmers may therefore perceive transition to SCP as very complex. The Dual Indicator Set for Crop Protection Sustainability (DISCUSS) can handle this complexity. To provide targeted support throughout the transition to SCP, complexity capture must be synchronised with the time course of on-farm decision-making. Tool use must be tuned to farmer awareness and appropriate level of data in consecutive stages. This paper thus explores the potential functionalities of DISCUSS in relation to both complexity and time. Results from apple and potato crop protection show three potential functions: DISCUSS can be used as (1) a simulation tool for communication and decision support, (2) an assessment and monitoring tool, and (3) a discussion support tool for farmer groups. Analysis of these functionalities using a framework for guiding on-farm sustainability assessment and strategic decision-making shows how each functionality can support the consecutive steps of transition to SCP, i.e. using the right tool functionality at the right time. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development.

    Science.gov (United States)

    Das, Sujaan; Lemgruber, Leandro; Tay, Chwen L; Baum, Jake; Meissner, Markus

    2017-08-15

    The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated. Of the two actin genes in P. falciparum, actin-1 (pfact1) is ubiquitously expressed in all life-cycle stages and is thought to be required for erythrocyte invasion, although its functions during parasite development are unknown, and definitive in vivo characterisation during invasion is lacking. Here we have used a conditional Cre-lox system to investigate the functions of PfACT1 during P. falciparum blood-stage development and host cell invasion. We demonstrate that PfACT1 is crucially required for segregation of the plastid-like organelle, the apicoplast, and for efficient daughter cell separation during the final stages of cytokinesis. Surprisingly, we observe that egress from the host cell is not an actin-dependent process. Finally, we show that parasites lacking PfACT1 are capable of microneme secretion, attachment and formation of a junction with the erythrocyte, but are incapable of host cell invasion. This study provides important mechanistic insights into the definitive essential functions of PfACT1 in P. falciparum, which are not only of biological interest, but owing to functional divergence from mammalian actins, could also form the basis for the development of novel therapeutics against apicomplexans.

  13. The Green Function cellular method and its relation to multiple scattering theory

    International Nuclear Information System (INIS)

    Butler, W.H.; Zhang, X.G.; Gonis, A.

    1992-01-01

    This paper investigates techniques for solving the wave equation which are based on the idea of obtaining exact local solutions within each potential cell, which are then joined to form a global solution. The authors derive full potential multiple scattering theory (MST) from the Lippmann-Schwinger equation and show that it as well as a closely related cellular method are techniques of this type. This cellular method appears to have all of the advantages of MST and the added advantage of having a secular matrix with only nearest neighbor interactions. Since this cellular method is easily linearized one can rigorously reduce electronic structure calculation to the problem of solving a nearest neighbor tight-binding problem

  14. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available Glucocorticoid-induced TNF receptor (GITR plays a crucial role in modulating immune response and inflammation, however the role of GITR in human cancers is poorly understood. In this study, we demonstrated that GITR is inactivated during tumor progression in Multiple Myeloma (MM through promoter CpG island methylation, mediating gene silencing in primary MM plasma cells and MM cell lines. Restoration of GITR expression in GITR deficient MM cells led to inhibition of MM proliferation in vitro and in vivo and induction of apoptosis. These findings were supported by the presence of induction of p21 and PUMA, two direct downstream targets of p53, together with modulation of NF-κB in GITR-overexpressing MM cells. Moreover, the unbalanced expression of GITR in clonal plasma cells correlated with MM disease progression, poor prognosis and survival. These findings provide novel insights into the pivotal role of GITR in MM pathogenesis and disease progression.

  15. Vocal fold motion impairment in patients with multiple system atrophy: evaluation of its relationship with swallowing function.

    Science.gov (United States)

    Higo, R; Tayama, N; Watanabe, T; Nitou, T; Takeuchi, S

    2003-07-01

    Vocal fold motion impairment (VFMI), especially vocal fold abductor paralysis, is frequently seen in multiple system atrophy (MSA). Since the regulation system of laryngeal function is closely related to swallowing function, swallowing function is considered to be more involved in MSA patients with VFMI than in patients that do not have VFMI. However, the relationship between dysphagia and VFMI in MSA patients has not been systematically explored. To elucidate the relationship between VFMI and dysphagia in MSA. We evaluated swallowing function of 36 MSA patients with and without VFMI, by videofluoroscopy, and investigated the relationship between VFMI and pharyngeal swallowing function. VFMI was found in 17 patients (47.2%). Patients with VFMI had advanced severity of the disease. Although there was a tendency for bolus stasis at the pyriform sinus and the upper oesophageal sphincter opening to be more involved in patients with VFMI, statistical analysis did not show significant differences in swallowing function of MSA patients between with and without VFMI. In contrast, patients who underwent a tracheotomy ultimately required tube feeding or a laryngectomy. Appearance of VFMI is a sign of disease progression but does not necessary mean patients should change their way of taking nutrition. However, MSA patients who need a tracheotomy might have advanced to a high-risk group for dysphagia. Appropriate evaluation and treatment for VFMI and dysphagia are required to maintain patients' quality of life in MSA.

  16. Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

    Directory of Open Access Journals (Sweden)

    Yoko Kimata-Ariga

    Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

  17. Method of applying single higher order polynomial basis function over multiple domains

    CSIR Research Space (South Africa)

    Lysko, AA

    2010-03-01

    Full Text Available A novel method has been devised where one set of higher order polynomial-based basis functions can be applied over several wire segments, thus permitting to decouple the number of unknowns from the number of segments, and so from the geometrical...

  18. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

  19. Social Function in Multiple X and Y Chromosome Disorders: XXY, XYY, XXYY, XXXY

    Science.gov (United States)

    Visootsak, Jeannie; Graham, John M., Jr.

    2009-01-01

    Klinefelter syndrome (47,XXY) was initially described in the context of its endocrinologic and physical features; however, subsequent studies have revealed specific impairments in verbal skills and social functioning. Males with sex chromosomal aneuploidies are known to have variability in their developmental profile with the majority presenting…

  20. GWIS: Genome-Wide Inferred Statistics for Functions of Multiple Phenotypes

    NARCIS (Netherlands)

    Nieuwboer, H.A.; Pool, R.; Dolan, C.V.; Boomsma, D.I.; Nivard, M.G.

    2016-01-01

    Here we present a method of genome-wide inferred study (GWIS) that provides an approximation of genome-wide association study (GWAS) summary statistics for a variable that is a function of phenotypes for which GWAS summary statistics, phenotypic means, and covariances are available. A GWIS can be

  1. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta

    2010-01-01

    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...

  2. Her versus his migraine: multiple sex differences in brain function and structure.

    Science.gov (United States)

    Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

    2012-08-01

    Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

  3. Predictive value of different conventional and non-conventional MRI-parameters for specific domains of cognitive function in multiple sclerosis.

    Science.gov (United States)

    Pinter, Daniela; Khalil, Michael; Pichler, Alexander; Langkammer, Christian; Ropele, Stefan; Marschik, Peter B; Fuchs, Siegrid; Fazekas, Franz; Enzinger, Christian

    2015-01-01

    While many studies correlated cognitive function with changes in brain morphology in multiple sclerosis (MS), few of them used a multi-parametric approach in a single dataset so far. We thus here assessed the predictive value of different conventional and quantitative MRI-parameters both for overall and domain-specific cognitive performance in MS patients from a single center. 69 patients (17 clinically isolated syndrome, 47 relapsing-remitting MS, 5 secondary-progressive MS) underwent the "Brief Repeatable Battery of Neuropsychological Tests" assessing overall cognition, cognitive efficiency and memory function as well as MRI at 3 Tesla to obtain T2-lesion load (T2-LL), normalized brain volume (global brain volume loss), normalized cortical volume (NCV), normalized thalamic volume (NTV), normalized hippocampal volume (NHV), normalized caudate nuclei volume (NCNV), basal ganglia R2* values (iron deposition) and magnetization transfer ratios (MTRs) for cortex and normal appearing brain tissue (NABT). Regression models including clinical, demographic variables and MRI-parameters explained 22-27% of variance of overall cognition, 17-26% of cognitive efficiency and 22-23% of memory. NCV, T2-LL and MTR of NABT were the strongest predictors of overall cognitive function. Cognitive efficiency was best predicted by NCV, T2-LL and iron deposition in the basal ganglia. NTV was the strongest predictor for memory function and NHV was particularly related to memory function. The predictive value of distinct MRI-parameters differs for specific domains of cognitive function, with a greater impact of cortical volume, focal and diffuse white matter abnormalities on overall cognitive function, an additional role of basal ganglia iron deposition on cognitive efficiency, and thalamic and hippocampal volume on memory function. This suggests the usefulness of using multiparametric MRI to assess (micro)structural correlates of different cognitive constructs.

  4. Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

    Science.gov (United States)

    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Using Functional Electrical Stimulation Mediated by Iterative Learning Control and Robotics to Improve Arm Movement for People With Multiple Sclerosis.

    Science.gov (United States)

    Sampson, Patrica; Freeman, Chris; Coote, Susan; Demain, Sara; Feys, Peter; Meadmore, Katie; Hughes, Ann-Marie

    2016-02-01

    Few interventions address multiple sclerosis (MS) arm dysfunction but robotics and functional electrical stimulation (FES) appear promising. This paper investigates the feasibility of combining FES with passive robotic support during virtual reality (VR) training tasks to improve upper limb function in people with multiple sclerosis (pwMS). The system assists patients in following a specified trajectory path, employing an advanced model-based paradigm termed iterative learning control (ILC) to adjust the FES to improve accuracy and maximise voluntary effort. Reaching tasks were repeated six times with ILC learning the optimum control action from previous attempts. A convenience sample of five pwMS was recruited from local MS societies, and the intervention comprised 18 one-hour training sessions over 10 weeks. The accuracy of tracking performance without FES and the amount of FES delivered during training were analyzed using regression analysis. Clinical functioning of the arm was documented before and after treatment with standard tests. Statistically significant results following training included: improved accuracy of tracking performance both when assisted and unassisted by FES; reduction in maximum amount of FES needed to assist tracking; and less impairment in the proximal arm that was trained. The system was well tolerated by all participants with no increase in muscle fatigue reported. This study confirms the feasibility of FES combined with passive robot assistance as a potentially effective intervention to improve arm movement and control in pwMS and provides the basis for a follow-up study.

  6. Evaluation of Multiple-Sampling Function used with a Microtek flatbed scanner for Radiation Dosimetry Calibration of EBT2 Film

    International Nuclear Information System (INIS)

    Chang, Liyun; Ho, Sheng-Yow; Ding, Hueisch-Jy; Hwang, Ing-Ming; Chen, Pang-Yu; Lee, Tsair-Fwu

    2016-01-01

    The radiochromic EBT2 film is a widely used quality assurance device for radiation therapy. This study evaluated the film calibration performance of the multiple-sampling function, a function of the ScanWizard Pro scanning software provided by the manufacturer, when used with Microtek 9800XL plus (9800XL + ) flatbed scanner. By using the PDD method, each one of the eight EBT2 films, four delivered by 290 monitor unit (MU) and four by 88 MU via 6-MV photon beams, was tightly sandwiched in a 30 3 -cm 3 water equivalent polystyrene phantom prior to irradiation. Before and after irradiation, all films were scanned using the Microtek 9800XL + scanner with five different modes of the multiple-sampling function, which could generate the image with the averaged result of multiple-sampling. The net optical densities (netOD) on the beam central axis of film were assigned to corresponding depth doses for calibration. For each sampling mode with either delivered MU, the depth-dose uncertainty of a single film from repeated scans and that of a single scan of the four films were analyzed. Finally, the calibration error and the combined calibration uncertainty between film determined depth-doses and delivered depth-doses were calculated and evaluated for each sampling mode. All standard deviations and the calibration error were demonstrated to be unrelated to the number of sampling lines. The calibration error of the 2-line and 16-line mode was within 3 cGy and better than that of the other modes. The combined uncertainty of the 2-line mode was the lowest, which was generally less than 6 cGy except for the delivered dose around 100 cGy. The evaluation described herein revealed that the EBT2 film calibrated with the 2-line mode has relatively lower error, scanning time and combined uncertianty. Therefore, it is recommended for routine EBT2 film calibration and verification of treatment plans.

  7. Human factors considerations for training astronauts to function effectively in multiple environments

    Science.gov (United States)

    Cohen, Malcolm M.

    1991-01-01

    This paper reviews some of the basic issues involved in training individuals to function appropriately under the several conditions that comprise the aerospace environment. The topic of transfer of training is examined in some detail, and the use of high-fidelity simulators in various training programs is discussed. Both current and classical techniques used to train astronauts are noted, and some relatively new and innovative training techniques and methods are described. Particularly, the paper discusses an important aspect of functioning appropriately in a given environment that is based on how well the operator calibrates his motor activity for that specific environment. The role of motor-sensory feedback for the acquisition of motor skills is discussed in the context of training.

  8. New Caledonian crows attend to multiple functional properties of complex tools.

    Science.gov (United States)

    St Clair, James J H; Rutz, Christian

    2013-11-19

    The ability to attend to the functional properties of foraging tools should affect energy-intake rates, fitness components and ultimately the evolutionary dynamics of tool-related behaviour. New Caledonian crows Corvus moneduloides use three distinct tool types for extractive foraging: non-hooked stick tools, hooked stick tools and tools cut from the barbed edges of Pandanus spp. leaves. The latter two types exhibit clear functional polarity, because of (respectively) a single terminal, crow-manufactured hook and natural barbs running along one edge of the leaf strip; in each case, the 'hooks' can only aid prey capture if the tool is oriented correctly by the crow during deployment. A previous experimental study of New Caledonian crows found that subjects paid little attention to the barbs of supplied (wide) pandanus tools, resulting in non-functional tool orientation during foraging. This result is puzzling, given the presumed fitness benefits of consistently orienting tools functionally in the wild. We investigated whether the lack of discrimination with respect to (wide) pandanus tool orientation also applies to hooked stick tools. We experimentally provided subjects with naturalistic replica tools in a range of orientations and found that all subjects used these tools correctly, regardless of how they had been presented. In a companion experiment, we explored the extent to which normally co-occurring tool features (terminal hook, curvature of the tool shaft and stripped bark at the hooked end) inform tool-orientation decisions, by forcing birds to deploy 'unnatural' tools, which exhibited these traits at opposite ends. Our subjects attended to at least two of the three tool features, although, as expected, the location of the hook was of paramount importance. We discuss these results in the context of earlier research and propose avenues for future work.

  9. Binding of multiple features in memory by high-functioning adults with autism spectrum disorder

    OpenAIRE

    Bowler, D. M.; Gaigg, S. B.; Gardiner, J. M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) wo...

  10. Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

    Science.gov (United States)

    2015-10-01

    including the Wechsler Intelligence Scale for Children (WISC-IV) for verbal and non-verbal intelligence; the Boston Naming Test , which evaluates a...demonstrated congruency between fMRI mappings and patient performance; 2) testing of the fMRI methods we developed for use in POMS patients was carried out...adaptive functional reorganization as a way to explain how some early-stage MS patients are able to perform well in clinical cognitive testing

  11. The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

    Directory of Open Access Journals (Sweden)

    Natalia O. Kalinina

    2018-02-01

    Full Text Available The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribosepolymerase (PARP, which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses.

  12. Functional decline and herpes zoster in older people: an interplay of multiple factors.

    Science.gov (United States)

    2015-12-01

    Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

  13. The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

    Science.gov (United States)

    Kalinina, Natalia O.; Makarova, Svetlana; Makhotenko, Antonida; Love, Andrew J.; Taliansky, Michael

    2018-01-01

    The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribose)polymerase (PARP), which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses. PMID:29479362

  14. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

    Science.gov (United States)

    Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

    2017-01-01

    Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

  15. A method for multiple sequential analyses of macrophage functions using a small single cell sample

    Directory of Open Access Journals (Sweden)

    F.R.F. Nascimento

    2003-09-01

    Full Text Available Microbial pathogens such as bacillus Calmette-Guérin (BCG induce the activation of macrophages. Activated macrophages can be characterized by the increased production of reactive oxygen and nitrogen metabolites, generated via NADPH oxidase and inducible nitric oxide synthase, respectively, and by the increased expression of major histocompatibility complex class II molecules (MHC II. Multiple microassays have been developed to measure these parameters. Usually each assay requires 2-5 x 10(5 cells per well. In some experimental conditions the number of cells is the limiting factor for the phenotypic characterization of macrophages. Here we describe a method whereby this limitation can be circumvented. Using a single 96-well microassay and a very small number of peritoneal cells obtained from C3H/HePas mice, containing as little as <=2 x 10(5 macrophages per well, we determined sequentially the oxidative burst (H2O2, nitric oxide production and MHC II (IAk expression of BCG-activated macrophages. More specifically, with 100 µl of cell suspension it was possible to quantify H2O2 release and nitric oxide production after 1 and 48 h, respectively, and IAk expression after 48 h of cell culture. In addition, this microassay is easy to perform, highly reproducible and more economical.

  16. Method to obtain g-functions for multiple precast quadratic pile heat exchangers

    DEFF Research Database (Denmark)

    Pagola, Maria Alberdi; Jensen, Rasmus Lund; Madsen, Søren

    The average fluid temperature circulating through the ground loop is one of the main parameters required when choosing the most adequate heat pump for a ground source heat pump installation. Besides, the analysis of the fluid temperature over time will show the sustainability of the energy supply...... over the lifetime of the installation. The average fluid temperature is subjected to the type of ground heat exchangers and the thermal interactions between them, which also depend on the soil thermal properties. For the case of precast piles, the thermal interactions become significant...... as they are usually placed within short distances (0.5 to 4 metres). Fast models that can account for these interactions are required to enable feasibility studies and support the design phase. Besides, since pile heat exchangers have a main structural role, it is also relevant to develop models that can determine...... the temperature changes that the foundation might be subjected to, to assess thermo-mechanical implications. 3D finite element model (FEM) computation of the thermal behaviour of multiple pile heat exchanger foundations is not cost effective nor for feasibility studies, nor for most design applications. Therefore...

  17. Exploring resting-state EEG brain oscillatory activity in relation to cognitive functioning in multiple sclerosis.

    Science.gov (United States)

    Keune, Philipp M; Hansen, Sascha; Weber, Emily; Zapf, Franziska; Habich, Juliane; Muenssinger, Jana; Wolf, Sebastian; Schönenberg, Michael; Oschmann, Patrick

    2017-09-01

    Neurophysiologic monitoring parameters related to cognition in Multiple Sclerosis (MS) are sparse. Previous work reported an association between magnetoencephalographic (MEG) alpha-1 activity and information processing speed. While this remains to be replicated by more available electroencephalographic (EEG) methods, also other established EEG markers, e.g. the slow-wave/fast-wave ratio (theta/beta ratio), remain to be explored in this context. Performance on standard tests addressing information processing speed and attention (Symbol-Digit Modalities Test, SDMT; Test of Attention Performance, TAP) was examined in relation to resting-state EEG alpha-1 and alpha-2 activity and the theta/beta ratio in 25MS patients. Increased global alpha-1 and alpha-2 activity and an increased frontal theta/beta ratio (pronounced slow-wave relative to fast-wave activity) were associated with lower SDMT processing speed. In an exploratory analysis, clinically impaired attention was associated with a significantly increased frontal theta/beta ratio whereas alpha power did not show sensitivity to clinical impairment. EEG global alpha power and the frontal theta/beta ratio were both associated with attention. The theta/beta ratio involved potential clinical sensitivity. Resting-state EEG recordings can be obtained during the routine clinical process. The examined resting-state measures may represent feasible monitoring parameters in MS. This notion should be explored in future intervention studies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  18. Functional Outcomes of Multiple Sural Nerve Grafts for Facial Nerve Defects after Tumor-Ablative Surgery

    Directory of Open Access Journals (Sweden)

    Myung Chul Lee

    2015-07-01

    Full Text Available BackgroundFunctional restoration of the facial expression is necessary after facial nerve resection to treat head and neck tumors. This study was conducted to evaluate the functional outcomes of patients who underwent facial nerve cable grafting immediately after tumor resection.MethodsPatients who underwent cable grafting from April 2007 to August 2011 were reviewed, in which a harvested branch of the sural nerve was grafted onto each facial nerve division. Twelve patients underwent facial nerve cable grafting after radical parotidectomy, total parotidectomy, or schwannoma resection, and the functional facial expression of each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results were analyzed according to patient age, follow-up duration, and the use of postoperative radiation therapy.ResultsAmong the 12 patients who were evaluated, the mean follow-up duration was 21.8 months, the mean age at the time of surgery was 42.8 years, and the mean facial expression score was 14.6 points, indicating moderate dysfunction. Facial expression scores were not influenced by age at the time of surgery, follow-up duration, or the use of postoperative radiation therapy.ConclusionsThe results of this study indicate that facial nerve cable grafting using the sural nerve can restore facial expression. Although patients were provided with appropriate treatment, the survival rate for salivary gland cancer was poor. We conclude that immediate facial nerve reconstruction is a worthwhile procedure that improves quality of life by allowing the recovery of facial expression, even in patients who are older or may require radiation therapy.

  19. Modelling of coil-loaded wire antenna using composite multiple domain basis functions

    CSIR Research Space (South Africa)

    Lysko, AA

    2010-03-01

    Full Text Available - tional Electromagnetics, Artech House, 2001. 3. Rogers, S. D. and C. M. Butler, \\An e–cient curved-wire integral equation solution technique," IEEE Trans. Ant. and Propag., 70{79, Vol. 49, Jan. 2001. 4. Mosig, J. and E. Suter, \\A multilevel divide.... 8. Wan, J. X., J. Lei, and C.-H. Liang, \\An e–cient analysis of large-scale periodic microstrip antenna arrays using the characteristic basis function method," Progress In Electromagnetics Research, PIER 50, 61{81, 2005. 9. Taguchi, M., K...

  20. A differential transformation approach for solving functional differential equations with multiple delays

    Science.gov (United States)

    Rebenda, Josef; Šmarda, Zdeněk

    2017-07-01

    In the paper an efficient semi-analytical approach based on the method of steps and the differential transformation is proposed for numerical approximation of solutions of functional differential models of delayed and neutral type on a finite interval of arbitrary length, including models with several constant delays. Algorithms for both commensurate and non-commensurate delays are described, applications are shown in examples. Validity and efficiency of the presented algorithms is compared with the variational iteration method, the Adomian decomposition method and the polynomial least squares method numerically. Matlab package DDE23 is used to produce reference numerical values.

  1. Functional analyses of multiple lichenin-degrading enzymes from the rumen bacterium Ruminococcus albus 8.

    Science.gov (United States)

    Iakiviak, Michael; Mackie, Roderick I; Cann, Isaac K O

    2011-11-01

    Ruminococcus albus 8 is a fibrolytic ruminal bacterium capable of utilization of various plant cell wall polysaccharides. A bioinformatic analysis of a partial genome sequence of R. albus revealed several putative enzymes likely to hydrolyze glucans, including lichenin, a mixed-linkage polysaccharide of glucose linked together in β-1,3 and β-1,4 glycosidic bonds. In the present study, we demonstrate the capacity of four glycoside hydrolases (GHs), derived from R. albus, to hydrolyze lichenin. Two of the genes encoded GH family 5 enzymes (Ra0453 and Ra2830), one gene encoded a GH family 16 enzyme (Ra0505), and the last gene encoded a GH family 3 enzyme (Ra1595). Each gene was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. Upon screening on a wide range of substrates, Ra0453, Ra2830, and Ra0505 displayed different hydrolytic properties, as they released unique product profiles. The Ra1595 protein, predicted to function as a β-glucosidase, preferred cleavage of a nonreducing end glucose when linked by a β-1,3 glycosidic bond to the next glucose residue. The major product of Ra0505 hydrolysis of lichenin was predicted to be a glucotriose that was degraded only by Ra0453 to glucose and cellobiose. Most importantly, the four enzymes functioned synergistically to hydrolyze lichenin to glucose, cellobiose, and cellotriose. This lichenin-degrading enzyme mix should be of utility as an additive to feeds administered to monogastric animals, especially those high in fiber.

  2. Examining Multiple Sources of Differential Item Functioning on the Clinician & Group CAHPS® Survey

    Science.gov (United States)

    Rodriguez, Hector P; Crane, Paul K

    2011-01-01

    Objective To evaluate psychometric properties of a widely used patient experience survey. Data Sources English-language responses to the Clinician & Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS®) survey (n = 12,244) from a 2008 quality improvement initiative involving eight southern California medical groups. Methods We used an iterative hybrid ordinal logistic regression/item response theory differential item functioning (DIF) algorithm to identify items with DIF related to patient sociodemographic characteristics, duration of the physician–patient relationship, number of physician visits, and self-rated physical and mental health. We accounted for all sources of DIF and determined its cumulative impact. Principal Findings The upper end of the CG-CAHPS® performance range is measured with low precision. With sensitive settings, some items were found to have DIF. However, overall DIF impact was negligible, as 0.14 percent of participants had salient DIF impact. Latinos who spoke predominantly English at home had the highest prevalence of salient DIF impact at 0.26 percent. Conclusions The CG-CAHPS® functions similarly across commercially insured respondents from diverse backgrounds. Consequently, previously documented racial and ethnic group differences likely reflect true differences rather than measurement bias. The impact of low precision at the upper end of the scale should be clarified. PMID:22092021

  3. Multiple functions and essential roles of nuclear receptor coactivators of bHLH-PAS family.

    Science.gov (United States)

    Pecenova, L; Farkas, Robert

    2016-07-01

    Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numerous metabolic pathways, and can be misregulated in many types of cancers. Their enormous functional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and highlight some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways.

  4. Humic acids: Structural properties and multiple functionalities for novel technological developments.

    Science.gov (United States)

    de Melo, Bruna Alice Gomes; Motta, Fernanda Lopes; Santana, Maria Helena Andrade

    2016-05-01

    Humic acids (HAs) are macromolecules that comprise humic substances (HS), which are organic matter distributed in terrestrial soil, natural water, and sediment. HAs differ from the other HS fractions (fulvic acid and humins) in that they are soluble in alkaline media, partially soluble in water, and insoluble in acidic media. Due to their amphiphilic character, HAs form micelle-like structures in neutral to acidic conditions, which are useful in agriculture, pollution remediation, medicine and pharmaceuticals. HAs have undefined compositions that vary according to the origin, process of obtainment, and functional groups present in their structures, such as quinones, phenols, and carboxylic acids. Quinones are responsible for the formation of reactive oxygen species (ROS) in HAs, which are useful for wound healing and have fungicidal/bactericidal properties. Phenols and carboxylic acids deprotonate in neutral and alkaline media and are responsible for various other functions, such as the antioxidant and anti-inflammatory properties of HAs. In particular, the presence of phenolic groups in HAs provides antioxidant properties due to their free radical scavenging capacity. This paper describes the main multifunctionalities of HAs associated with their structures and properties, focusing on human health applications, and we note perspectives that may lead to novel technological developments. To the best of our knowledge, this is the first review to address this topic from this approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  6. Epidemiological characteristics and functional disability of multiple sclerosis patients in Kosovo.

    Science.gov (United States)

    Zeqiraj, Kamber; Kruja, Jera; Kabashi, Serbeze; Muçaj, Sefedin

    2014-01-01

    Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female--male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).

  7. Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6

    Science.gov (United States)

    Swaminathan, Bhairavi; Cuapio, Angélica; Alloza, Iraide; Matesanz, Fuencisla; Alcina, Antonio; García-Barcina, Maria; Fedetz, Maria; Fernández, Óscar; Lucas, Miguel; Órpez, Teresa; Pinto-Medel, Mª Jesus; Otaegui, David; Olascoaga, Javier; Urcelay, Elena; Ortiz, Miguel A.; Arroyo, Rafael; Oksenberg, Jorge R.; Antigüedad, Alfredo; Tolosa, Eva; Vandenbroeck, Koen

    2013-01-01

    CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (P max(T) permutation = 1×10−4). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naïve cells, P = 0.0001; CD8+ naïve cells, P<0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells. PMID:23638056

  8. Constraints on signaling network logic reveal functional subgraphs on Multiple Myeloma OMIC data.

    Science.gov (United States)

    Miannay, Bertrand; Minvielle, Stéphane; Magrangeas, Florence; Guziolowski, Carito

    2018-03-21

    The integration of gene expression profiles (GEPs) and large-scale biological networks derived from pathways databases is a subject which is being widely explored. Existing methods are based on network distance measures among significantly measured species. Only a small number of them include the directionality and underlying logic existing in biological networks. In this study we approach the GEP-networks integration problem by considering the network logic, however our approach does not require a prior species selection according to their gene expression level. We start by modeling the biological network representing its underlying logic using Logic Programming. This model points to reachable network discrete states that maximize a notion of harmony between the molecular species active or inactive possible states and the directionality of the pathways reactions according to their activator or inhibitor control role. Only then, we confront these network states with the GEP. From this confrontation independent graph components are derived, each of them related to a fixed and optimal assignment of active or inactive states. These components allow us to decompose a large-scale network into subgraphs and their molecular species state assignments have different degrees of similarity when compared to the same GEP. We apply our method to study the set of possible states derived from a subgraph from the NCI-PID Pathway Interaction Database. This graph links Multiple Myeloma (MM) genes to known receptors for this blood cancer. We discover that the NCI-PID MM graph had 15 independent components, and when confronted to 611 MM GEPs, we find 1 component as being more specific to represent the difference between cancer and healthy profiles.

  9. Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction

    NARCIS (Netherlands)

    Poll-The, B. T.; Saudubray, J. M.; Ogier, H.; Schutgens, R. B.; Wanders, R. J.; Schrakamp, G.; van den Bosch, H.; Trijbels, J. M.; Poulos, A.; Moser, H. W.

    1986-01-01

    Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development. An elevated plasma phytanic acid concentration and a deficient phytanic acid

  10. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

  11. Effects of iodinated contrast media on renal function in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Jacob, H.M.

    1980-01-01

    Case histories of 89 patients with definite myoloma of the years 1959 to 1974 were investigated in a retrospective study. 41 intravenous urographies were carried out in 31 of these patients. There was no correlation between deterioration of the renal function and contrast medium application. Relevant literature on the subject has been compiled. By 1979, 19 case studies and 5 general studies had been published which have been summarized in tables in the present study. Analyses of these case histories have shown that acute renal failure was often due to other causes and not to contrast medium application. If these cases are left out of account 8 cases remain in which lethal renal failure occurred after intravenous urography of myeloma patients. The diiodinated contrast media formerly used was less well tolerated than the present triiodinated contrast media. Further risk factors were dehydratation and/or abdominal compression. Both measures are no longer employed in intravenous urography. (orig./MG) [de

  12. A semiconductor metasurface with multiple functionalities: A polarizing beam splitter with simultaneous focusing ability

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Hyung; Jin Jung, Myoung; Ho Song, Seok, E-mail: shsong@hanyang.ac.kr [Department of Physics, Hanyang University, Seoul (Korea, Republic of); Woong Yoon, Jae; Magnusson, Robert [Department of Electrical Engineering, University of Texas–Arlington, Arlington, Texas 76019 (United States); Kyun Hong, Jong [Department of Electrical Engineering, Hanyang University, Seoul (Korea, Republic of)

    2014-06-09

    We propose a semiconductor metasurface that simultaneously performs two independent functions: focusing and polarization filtering. The wavefronts of the reflected and transmitted light distributions are precisely manipulated by spatial parametric variation of a subwavelength thin-film Si grating, which inherently possesses polarization filtering properties. We design a 12-μm-wide metasurface containing only nineteen Si grating ridges. Under a 10-μm-wide unpolarized Gaussian beam incidence at wavelength of 1.55 μm, the resulting device shows promising theoretical performance with high power efficiency exceeding 80% and polarization extinction ratio of ∼10 dB with focal spot diameters near 1–2 μm.

  13. Binding of multiple features in memory by high-functioning adults with autism spectrum disorder.

    Science.gov (United States)

    Bowler, Dermot M; Gaigg, Sebastian B; Gardiner, John M

    2014-09-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) would be tested in a later memory test. In a second experiment, participants studied similar grids and were told that they would be tested on object-location or object-colour combinations. Recognition of combinations was significantly diminished in ASD, which survived covarying performance on the Color Trails Test (D'Elia et al. Color trails test. Professional manual. Psychological Assessment Resources, Lutz, 1996), a test of executive difficulties. The findings raise the possibility that medial temporal as well as frontal lobe processes are dysfunctional in ASD.

  14. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Science.gov (United States)

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  15. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  16. Evidence implicating the Ras pathway in multiple CD28 costimulatory functions in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Sujit V Janardhan

    Full Text Available CD28 costimulation is a critical event in the full activation of CD4(+ T cells that augments cytokine gene transcription, promotes cytokine mRNA stability, prevents induction of anergy, increases cellular metabolism, and increases cell survival. However, despite extensive biochemical analysis of the signaling events downstream of CD28, molecular pathways sufficient to functionally replace the diverse aspects of CD28-mediated costimulation in normal T cells have not been identified. Ras/MAPK signaling is a critical pathway downstream of T cell receptor stimulation, but its role in CD28-mediated costimulation has been controversial. We observed that physiologic CD28 costimulation caused a relocalization of the RasGEF RasGRP to the T cell-APC interface by confocal microscopy. In whole cell biochemical analysis, CD28 cross-linking with either anti-CD28 antibody or B7.1-Ig augmented TCR-induced Ras activation. To determine whether Ras signaling was sufficient to functionally mimic CD28 costimulation, we utilized an adenoviral vector encoding constitutively active H-Ras (61L to transduce normal, Coxsackie-Adenovirus Receptor (CAR transgenic CD4(+ T cells. Like costimulation via CD28, active Ras induced AKT, JNK and ERK phosphorylation. In addition, constitutive Ras signaling mimicked the ability of CD28 to costimulate IL-2 protein secretion, prevent anergy induction, increase glucose uptake, and promote cell survival. Importantly, we also found that active Ras mimicked the mechanism by which CD28 costimulates IL-2 production: by increasing IL-2 gene transcription, and promoting IL-2 mRNA stability. Finally, active Ras was able to induce IL-2 production when combined with ionomycin stimulation in a MEK-1-dependent fashion. Our results are consistent with a central role for Ras signaling in CD28-mediated costimulation.

  17. Measuring the impact of multiple sclerosis on psychosocial functioning: the development of a new self-efficacy scale.

    Science.gov (United States)

    Airlie, J; Baker, G A; Smith, S J; Young, C A

    2001-06-01

    To develop a scale to measure self-efficacy in neurologically impaired patients with multiple sclerosis and to assess the scale's psychometric properties. Cross-sectional questionnaire study in a clinical setting, the retest questionnaire returned by mail after completion at home. Regional multiple sclerosis (MS) outpatient clinic or the Clinical Trials Unit (CTU) at a large neuroscience centre in the UK. One hundred persons with MS attending the Walton Centre for Neurology and Neurosurgery and Clatterbridge Hospital, Wirral, as outpatients. Cognitively impaired patients were excluded at an initial clinic assessment. Patients were asked to provide demographic data and complete the self-efficacy scale along with the following validated scales: Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale, Impact, Stigma and Mastery and Rankin Scales. The Rankin Scale and Barthel Index were also assessed by the physician. A new 11-item self-efficacy scale was constructed consisting of two domains of control and personal agency. The validity of the scale was confirmed using Cronbach's alpha analysis of internal consistency (alpha = 0.81). The test-retest reliability of the scale over two weeks was acceptable with an intraclass correlation coefficient of 0.79. Construct validity was investigated using Pearson's product moment correlation coefficient resulting in significant correlations with depression (r= -0.52) anxiety (r =-0.50) and mastery (r= 0.73). Multiple regression analysis demonstrated that these factors accounted for 70% of the variance of scores on the self-efficacy scale, with scores on mastery, anxiety and perceived disability being independently significant. Assessment of the psychometric properties of this new self-efficacy scale suggest that it possesses good validity and reliability in patients with multiple sclerosis.

  18. Functional trait composition of aquatic plants can serve to disentangle multiple interacting stressors in lowland streams

    Energy Technology Data Exchange (ETDEWEB)

    Baattrup-Pedersen, Annette, E-mail: abp@bios.au.dk [Department of Bioscience, Aarhus University, Vejlsøvej 25, P.O. Box 314, DK-8600 Silkeborg (Denmark); Göthe, Emma [Department of Bioscience, Aarhus University, Vejlsøvej 25, P.O. Box 314, DK-8600 Silkeborg (Denmark); Riis, Tenna [Department of Bioscience, Aarhus University, Ole Worms Allé 1, Building 1135, Room 217, DK-8000 Aarhus C (Denmark); O' Hare, Matthew T. [Centre for Ecology and Hydrology, Bush Estate, Penicuik EH26 0QB (United Kingdom)

    2016-02-01

    stress. The ability to disentangle several stressors is particularly important in lowland stream environments where several stressors act in concert since the impact of the most important stressor can be targeted first, which is essential to improve the ecological status. - Highlights: • Functional trait composition of aquatic plants can distinguish hydromorphological degradation from eutrophication in streams • A conceptual framework on how eutrophication and hydromorphological degradation interact on functional trait composition • Weed cutting can set aside light as a factor controlling trait-abundance pattern in eutrophic lowland streams.

  19. Functional trait composition of aquatic plants can serve to disentangle multiple interacting stressors in lowland streams

    International Nuclear Information System (INIS)

    Baattrup-Pedersen, Annette; Göthe, Emma; Riis, Tenna; O'Hare, Matthew T.

    2016-01-01

    stress. The ability to disentangle several stressors is particularly important in lowland stream environments where several stressors act in concert since the impact of the most important stressor can be targeted first, which is essential to improve the ecological status. - Highlights: • Functional trait composition of aquatic plants can distinguish hydromorphological degradation from eutrophication in streams • A conceptual framework on how eutrophication and hydromorphological degradation interact on functional trait composition • Weed cutting can set aside light as a factor controlling trait-abundance pattern in eutrophic lowland streams.

  20. Three-dimensional models of Mycobacterium tuberculosis proteins Rv1555, Rv1554 and their docking analyses with sildenafil, tadalafil, vardenafil drugs, suggest interference with quinol binding likely to affect protein's function.

    Science.gov (United States)

    Dash, Pallabini; Bala Divya, M; Guruprasad, Lalitha; Guruprasad, Kunchur

    2018-04-18

    Earlier based on bioinformatics analyses, we had predicted the Mycobacterium tuberculosis (M.tb) proteins; Rv1555 and Rv1554, among the potential new tuberculosis drug targets. According to the 'TB-drugome' the Rv1555 protein is 'druggable' with sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra) drugs. In the present work, we intended to understand via computer modeling studies, how the above drugs are likely to inhibit the M.tb protein's function. The three-dimensional computer models for M.tb proteins; Rv1555 and Rv1554 constructed on the template of equivalent membrane anchor subunits of the homologous E.coli quinol fumarate reductase respiratory protein complex, followed by drug docking analyses, suggested that the binding of above drugs interferes with quinol binding sites. Also, we experimentally observed the in-vitro growth inhibition of E.coli bacteria containing the homologous M.tb protein sequences with sildenafil and tadalafil drugs. The predicted binding sites of the drugs is likely to affect the above M.tb proteins function as quinol binding is known to be essential for electron transfer function during anaerobic respiration in the homologous E.coli protein complex. Therefore, sildenafil and related drugs currently used in the treatment of male erectile dysfunction targeting the human phosphodiesterase 5 enzyme may be evaluated for their plausible role as repurposed drugs to treat human tuberculosis.

  1. On functionally-graded crashworthy shape of conical structures for multiple load cases

    International Nuclear Information System (INIS)

    Pang, Tong; Li, Yinfeng; Kang, Hehe; Sun, Guangyong; Li, Qing; Fang, Jianguang

    2017-01-01

    Many studies on energy absorbers have been focused on tapered tubes because they have significant advantages in crashworthiness and provide a desired constant load-deflection response. However, few studies have been reported on tapered tubes with nonlinearly- variable diameters along the longitudinal direction. This paper presents thin-walled Functionally graded tapered tube (FGTT) with a diameter varying nonlinearly subject to axial (0°) and oblique (10°, 20°, 30°) impacts. To explore the advantages of FGTT, conventional Straight/Conical circular tube (SCT/CCT) with the same mass are compared; and FGTTs with a gradient exponent n > 1 are found to be preferable to others in terms of energy absorption capacity under small impact angles. Then, crashworthiness analyses of different crushing distances are conducted and it is found that under a large impact angle (e.g. 20°, 30°), FGTT with a short crushing distance (e.g. 40mm) have a higher mean crashing force than long crushing distance (e.g. 120 mm), especially for n > 1. In addition, the effect of geometric parameters, such as the gradient exponent n and diameter range ΔD between top (incident) and bottom (distal) diameters of FGTTs, are also studied and it is found that the FGTT with ΔD = 40 mm and n > 1 exhibits better crashworthiness than the others under small impact angles (0°, 10°). This paper demonstrates that such FGTT structures have a certain potential to be an energy absorber.

  2. Thymosin β4: multiple functions in protection, repair and regeneration of the mammalian heart.

    Science.gov (United States)

    Bollini, Sveva; Riley, Paul R; Smart, Nicola

    2015-01-01

    Despite recent improvements in interventional medicine, cardiovascular disease still represents the major cause of morbidity worldwide, with myocardial infarction being the most common cardiac injury. This has sustained the development of several regenerative strategies based on the use of stem cells and tissue engineering approaches in order to achieve cardiac repair and regeneration by enhancing coronary neovascularization, modulating acute inflammation and supporting myocardial regeneration to provide new functional muscle. The actin monomer binding peptide, Thymosin β4 (Tβ4), has recently been described as a powerful regenerative agent with angiogenic, anti-inflammatory and cardioprotective effects on the heart and which specifically acts on its resident cardiac progenitor cells. In this review we will discuss the state of the art regarding the many roles of Tβ4 in preserving and regenerating the mammalian heart, with specific attention to its ability to activate the quiescent adult epicardium and specific subsets of epicardial progenitor cells for repair. The therapeutic potential of Tβ4 for the treatment of cardiac failure is herein evaluated alongside existing, emerging and prospective novel treatments.

  3. On functionally-graded crashworthy shape of conical structures for multiple load cases

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Tong; Li, Yinfeng [Hunan University, Changsha (China); Kang, Hehe [Chongqing Changan Automobile Co. Ltd., Chongqing (China); Sun, Guangyong; Li, Qing [The University of Sydney, Sydney (Australia); Fang, Jianguang [University of Technology Sydney, Sydney (Australia)

    2017-06-15

    Many studies on energy absorbers have been focused on tapered tubes because they have significant advantages in crashworthiness and provide a desired constant load-deflection response. However, few studies have been reported on tapered tubes with nonlinearly- variable diameters along the longitudinal direction. This paper presents thin-walled Functionally graded tapered tube (FGTT) with a diameter varying nonlinearly subject to axial (0°) and oblique (10°, 20°, 30°) impacts. To explore the advantages of FGTT, conventional Straight/Conical circular tube (SCT/CCT) with the same mass are compared; and FGTTs with a gradient exponent n > 1 are found to be preferable to others in terms of energy absorption capacity under small impact angles. Then, crashworthiness analyses of different crushing distances are conducted and it is found that under a large impact angle (e.g. 20°, 30°), FGTT with a short crushing distance (e.g. 40mm) have a higher mean crashing force than long crushing distance (e.g. 120 mm), especially for n > 1. In addition, the effect of geometric parameters, such as the gradient exponent n and diameter range ΔD between top (incident) and bottom (distal) diameters of FGTTs, are also studied and it is found that the FGTT with ΔD = 40 mm and n > 1 exhibits better crashworthiness than the others under small impact angles (0°, 10°). This paper demonstrates that such FGTT structures have a certain potential to be an energy absorber.

  4. Response function of NaI(Tl) detectors and multiple backscattering of gamma rays in aluminium

    International Nuclear Information System (INIS)

    Sabharwal, Arvind D.; Singh, Manpreet; Singh, Bhajan; Sandhu, B.S.

    2008-01-01

    The response function, converting the observed pulse-height distribution of a NaI(Tl) detector to a true photon spectrum, is obtained experimentally with the help of an inverse matrix approach. The energy of gamma-ray photons continuously decreases as the number of scatterings increases in a sample having finite dimensions when one deals with the depth of the sample. The present experiments are undertaken to study the effect of target thickness on intensity distribution of gamma photons multiply backscattered from an aluminium target. A NaI(Tl) gamma-ray detector detects the photons backscattered from the aluminium target. The subtraction of analytically estimated singly scattered distribution from the observed intensity distribution (originating from interactions of primary gamma-ray photons with the target) results in multiply backscattered events. We observe that for each incident gamma photon energy, the number of multiply backscattered photons increases with increase in target thickness and then saturates at a particular target thickness called the saturation thickness (depth). Saturation thickness for multiply backscattering of gamma photons is found to decrease with increase in energy of incident gamma-ray photons

  5. Multiple Functions of the New Cytokine-Based Antimicrobial Peptide Thymic Stromal Lymphopoietin (TSLP

    Directory of Open Access Journals (Sweden)

    Louise Bjerkan

    2016-07-01

    Full Text Available Thymic stromal lymphopoietin (TSLP is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP, that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs. lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs, with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34 that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.

  6. Impacts of multiple stressors on ecosystem function: Leaf decomposition in constructed urban wetlands.

    Science.gov (United States)

    Mackintosh, Teresa J; Davis, Jenny A; Thompson, Ross M

    2016-01-01

    The impact of stormwater on stream biota is well documented, but less is known about the impacts on ecosystem processes, such as the breakdown of organic matter. This study sought to establish whether the degree of urbanisation affected rates of leaf-litter breakdown within constructed wetlands. A litter bag method was used to ascertain rate of decomposition along a gradient of urbanisation (total imperviousness, TI), in constructed wetlands in western and south-eastern Melbourne. A significant positive relationship between TI and breakdown rate was found in the south-eastern wetlands. The significant reduction in rate of invertebrate-mediated breakdown with increasing concentration of certain metals was consistent with other studies. However, overall there was an increase in rate of breakdown. Studies have shown that the effects of heavy metals can be negated if nutrient levels are high. Our results suggest that other parameters besides exposure to contaminants are likely to affect leaf litter breakdown. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability

    Directory of Open Access Journals (Sweden)

    Antonio Giorgio

    2017-11-01

    Full Text Available Pediatric-onset multiple sclerosis (POMS may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15 in comparison with age- and disability-matched AOMS patients (n = 14 and to normal controls (NC, n = 20. We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space. POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

  8. The influence of multiple sensory impairments on functional balance and difficulty with falls among U.S. adults.

    Science.gov (United States)

    Wilson, Samuel J; Garner, John C; Loprinzi, Paul D

    2016-06-01

    Studies have looked at the individual associations of sensory impairment on balance, but no population-based studies have examined their combined association on balance and difficulty with falls. Thus, the purpose of this study was to examine both the independent associations and combined associations of visual impairment, peripheral neuropathy, and self-reported hearing loss with the odds of reporting difficulty with falls and functional balance. Data from the 2003-2004 National Health and Nutrition Examination Survey were used. Vision and peripheral neuropathy were objectively measured, and hearing was self-reported. Balance testing consisted of a modified Romberg test. After exclusions, 1662 (40-85years of age) participants provided complete data on the study variables. Sensory impairment was associated with perceived difficulty of falls and functional balance. Participants who presented a single sensory impairment had 29% reduced odds of having functional balance (95% CI=0.54-0.93, p=0.01) and increased odds of reporting difficulty with falls by 61% (95% CI=0.99-2.60, p=0.05). Moreover, our multisensory models showed some evidence of a dose-response relationship, in that sensory impairment of multiple sensory systems was associated with worse balance (OR =0.59, CI=0.35-1.00, p=0.05) and perceived difficulty of falls (OR =5.02, 95% CI=1.99-12.66, p=0.002) when compared to those with less sensory impairment. Multiple sensory impairment is associated with significantly higher odds of both reporting difficulty with falls and balance dysfunction, which may lead to a subsequent fall, ultimately compromising the individual's health. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

    Directory of Open Access Journals (Sweden)

    Tibiriça Eduardo

    2010-01-01

    Full Text Available Abstract Background Cannabis sativa (also known as marijuana has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1 was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2. Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome. Conclusions The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.

  10. Impact of cognitive function and dysarthria on spoken language and perceived speech severity in multiple sclerosis

    Science.gov (United States)

    Feenaughty, Lynda

    Purpose: The current study sought to investigate the separate effects of dysarthria and cognitive status on global speech timing, speech hesitation, and linguistic complexity characteristics and how these speech behaviors impose on listener impressions for three connected speech tasks presumed to differ in cognitive-linguistic demand for four carefully defined speaker groups; 1) MS with cognitive deficits (MSCI), 2) MS with clinically diagnosed dysarthria and intact cognition (MSDYS), 3) MS without dysarthria or cognitive deficits (MS), and 4) healthy talkers (CON). The relationship between neuropsychological test scores and speech-language production and perceptual variables for speakers with cognitive deficits was also explored. Methods: 48 speakers, including 36 individuals reporting a neurological diagnosis of MS and 12 healthy talkers participated. The three MS groups and control group each contained 12 speakers (8 women and 4 men). Cognitive function was quantified using standard clinical tests of memory, information processing speed, and executive function. A standard z-score of ≤ -1.50 indicated deficits in a given cognitive domain. Three certified speech-language pathologists determined the clinical diagnosis of dysarthria for speakers with MS. Experimental speech tasks of interest included audio-recordings of an oral reading of the Grandfather passage and two spontaneous speech samples in the form of Familiar and Unfamiliar descriptive discourse. Various measures of spoken language were of interest. Suprasegmental acoustic measures included speech and articulatory rate. Linguistic speech hesitation measures included pause frequency (i.e., silent and filled pauses), mean silent pause duration, grammatical appropriateness of pauses, and interjection frequency. For the two discourse samples, three standard measures of language complexity were obtained including subordination index, inter-sentence cohesion adequacy, and lexical diversity. Ten listeners

  11. Chapter Four : Towards an Integration of Biodiversity–Ecosystem Functioning and Food Web Theory to Evaluate Relationships between Multiple Ecosystem Services

    NARCIS (Netherlands)

    Hines, J.; Putten, van der W.H.; Deyn, de G.B.; Wagg, C.; Voigt, W.; Mulder, C.; Weisser, W.W.; Engel, J.; Melian, C.; Scheu, S.; Birkhofer, K.; Ebeling, A.; Scherber, C.; Eisenhauer, N.

    2015-01-01

    Ecosystem responses to changes in species diversity are often studied individually. However, changes in species diversity can simultaneously influence multiple interdependent ecosystem functions. Therefore, an important challenge is to determine when and how changes in species diversity that

  12. Pathological changes of the chemosensory function in multiple sclerosis. An MRI study

    International Nuclear Information System (INIS)

    Schmidt, F.A.; Harms, L.; Fleiner, F.; Dahlslett, B.; Goektas, Oe.; Bohner, G.; Erb, K.; Luedemann, L.

    2011-01-01

    Purpose: To examine possible causes for olfactory and gustatory dysfunction in MS patients in a prospective study with MRI. Materials and Methods: 30 MS patients (21 women, 11 men, 22 - 65 years, diameter 42 years) were examined by MRI. The olfactory bulb (OB) and olfactory brain volume was correlated with the number and volume of MS lesions in the olfactory brain and the non-olfactory brain. Olfactory testing was performed using the Threshold-Discrimination-Identification Test (TDI), and gustatory function was tested using the Taste-Strips-Test (TST). Results: 33 % of the MS patients displayed olfactory dysfunction (8 % of the control group), and 17 % displayed gustatory dysfunction (5 % of the control group). There was a correlation between the olfactory brain volume and the number (r = -0.38, p < 0.05) and volume (r = -0.38, p < 0.05) of MS lesions in the olfactory brain. The olfactory brain volume correlated with the number of MS lesions in the non-olfactory brain (r = -0.48, p < 0.05). The volume of the left OB correlated with the volume of MS lesions in the olfactory brain (r = -0.42, p < 0.05), the number (r = 0.37, p < 0.05) and volume (r = 0.4, p < 0.05) of lesions in the left part of the olfactory brain and with the TST score (r = -0.45, p < 0.05). The TST score correlated with the volume of lesions in the left (r = -0.45, p < 0.05) and right part (r = -0.53, p < 0.05) of the olfactory brain. The TST score correlated with the number of lesions in the non-olfactory brain (r = -0.48, p < 0.05). Conclusion: The correlation between a higher number and volume of MS lesions in the olfactory brain with a decreased OB and olfactory brain volume could help to explain olfactory and gustatory dysfunction in MS patients. Just the left OB correlated with the number and volume of lesions in the olfactory brain. Manual segmentation was a suitable method for measuring OB and olfactory brain volume. (orig.)

  13. Evaluation of Multiple-Sampling Function used with a Microtek flatbed scanner for Radiation Dosimetry Calibration of EBT2 Film

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Liyun [Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung 82445, Taiwan (China); Ho, Sheng-Yow [Department of Nursing, Chang Jung Christian University, Tainan 71101, Taiwan (China); Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan (China); Ding, Hueisch-Jy [Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung 82445, Taiwan (China); Hwang, Ing-Ming [Department of Medical Imaging and Radiology, Shu Zen College of Medicine and Management, Kaohsiung 82144, Taiwan (China); Chen, Pang-Yu, E-mail: pangyuchen@yahoo.com.tw [Department of Radiation Oncology, Sinlau Christian Hospital, Tainan 70142, Taiwan (China); Lee, Tsair-Fwu, E-mail: tflee@kuas.edu.tw [Medical Physics and Informatics Laboratory, Department of Electronics Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan (China)

    2016-10-01

    The radiochromic EBT2 film is a widely used quality assurance device for radiation therapy. This study evaluated the film calibration performance of the multiple-sampling function, a function of the ScanWizard Pro scanning software provided by the manufacturer, when used with Microtek 9800XL plus (9800XL{sup +}) flatbed scanner. By using the PDD method, each one of the eight EBT2 films, four delivered by 290 monitor unit (MU) and four by 88 MU via 6-MV photon beams, was tightly sandwiched in a 30{sup 3}-cm{sup 3} water equivalent polystyrene phantom prior to irradiation. Before and after irradiation, all films were scanned using the Microtek 9800XL{sup +} scanner with five different modes of the multiple-sampling function, which could generate the image with the averaged result of multiple-sampling. The net optical densities (netOD) on the beam central axis of film were assigned to corresponding depth doses for calibration. For each sampling mode with either delivered MU, the depth-dose uncertainty of a single film from repeated scans and that of a single scan of the four films were analyzed. Finally, the calibration error and the combined calibration uncertainty between film determined depth-doses and delivered depth-doses were calculated and evaluated for each sampling mode. All standard deviations and the calibration error were demonstrated to be unrelated to the number of sampling lines. The calibration error of the 2-line and 16-line mode was within 3 cGy and better than that of the other modes. The combined uncertainty of the 2-line mode was the lowest, which was generally less than 6 cGy except for the delivered dose around 100 cGy. The evaluation described herein revealed that the EBT2 film calibrated with the 2-line mode has relatively lower error, scanning time and combined uncertianty. Therefore, it is recommended for routine EBT2 film calibration and verification of treatment plans.

  14. Synthesis of palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel for electrochemical detection of dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruiyi; Yang, Tingting [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China); Li, Zaijun, E-mail: zaijunli@jiangnan.edu.cn [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China); Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, Wuxi 214122 (China); Gu, Zhiguo; Wang, Guangli; Liu, Junkang [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China)

    2017-02-15

    Integration of noble metal nanomaterials on graphene nanosheets potentially paves one way to improve their electronic, chemical and electrochemical properties. The study reported synthesis of palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel composite (Pd@Au/N,S-MGA). The as-prepared composite offers a well-defined three-dimensional architecture with rich of mesopores. The Pd@Au nanoalloys were dispersed on the graphene framework networks and their active sites were fully exposed. The unique structure achieves to ultra high electron/ion conductivity, electrocatalytic activity and structural stability. The sensor based on the Pd@Au/N,S-MGA creates ultrasensitive electrochemical response towards dopamine due to significantly electrochemical synergy between Pd, Au and N,S-MGA. Its differential pulse voltammetric signal linearly increases with the increase of dopamine concentration in the range from 1.0 × 10{sup −9} M to 4.0 × 10{sup −5} M with the detection limit of 3.6 × 10{sup −10} M (S/N = 3). The analytical method provides the advantage of sensitivity, reproducibility, rapidity and long-term stability. It has been successfully applied in the detection of trace dopamine in biological samples. The study also opens a window on the electronic properties of graphene aerogel and metal nanomaterials as well their nanohybrids to meet needs of further applications as nanoelectronics in diagnosis, bioanalysis and catalysis. - Graphical abstract: We reported a new palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel. The sensor based on the nanohybrid exhibits ultrahigh sensitivity, reproducibility and stability to electrochemical detection of dopamine. - Highlights: • We reported Pd@A/nitrogen and sulphur-functionalized multiple graphene aerogel. • The nanohybrid offers unique three-dimensional architecture with rich of mesopores. • The architecture achieve to ultrahigh