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Sample records for functional analyses define

  1. Defining functional distances over Gene Ontology

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    del Pozo Angela

    2008-01-01

    Full Text Available Abstract Background A fundamental problem when trying to define the functional relationships between proteins is the difficulty in quantifying functional similarities, even when well-structured ontologies exist regarding the activity of proteins (i.e. 'gene ontology' -GO-. However, functional metrics can overcome the problems in the comparing and evaluating functional assignments and predictions. As a reference of proximity, previous approaches to compare GO terms considered linkage in terms of ontology weighted by a probability distribution that balances the non-uniform 'richness' of different parts of the Direct Acyclic Graph. Here, we have followed a different approach to quantify functional similarities between GO terms. Results We propose a new method to derive 'functional distances' between GO terms that is based on the simultaneous occurrence of terms in the same set of Interpro entries, instead of relying on the structure of the GO. The coincidence of GO terms reveals natural biological links between the GO functions and defines a distance model Df which fulfils the properties of a Metric Space. The distances obtained in this way can be represented as a hierarchical 'Functional Tree'. Conclusion The method proposed provides a new definition of distance that enables the similarity between GO terms to be quantified. Additionally, the 'Functional Tree' defines groups with biological meaning enhancing its utility for protein function comparison and prediction. Finally, this approach could be for function-based protein searches in databases, and for analysing the gene clusters produced by DNA array experiments.

  2. Normal Functions As A New Way Of Defining Computable Functions

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    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert’s system of recursive functions. Normal functions lack this disadvantage.

  3. Normal Functions as a New Way of Defining Computable Functions

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    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert's system of recursive functions. Normal functions lack this disadvantage.

  4. Spaces defined by the Paley function

    Energy Technology Data Exchange (ETDEWEB)

    Astashkin, S V [Samara State University, Samara (Russian Federation); Semenov, E M [Voronezh State University, Faculty of Mathematics, Voronezh (Russian Federation)

    2013-07-31

    The paper is concerned with Haar and Rademacher series in symmetric spaces, and also with the properties of spaces defined by the Paley function. In particular, the symmetric hull of the space of functions with uniformly bounded Paley function is found. Bibliography: 27 titles.

  5. On functions defined by sums of products of Bessel functions

    International Nuclear Information System (INIS)

    Martin, P A

    2008-01-01

    Various functions, defined as infinite series of products of Bessel functions of the first kind, are studied. Integral representations are obtained, and then used to deduce asymptotic approximations. Although several methods have been investigated (including power series expansions and integral transforms), methods based on Fourier series emerge as the most useful

  6. Defining functional dyspepsia Definiendo la dispepsia funcional

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    Fermín Mearin

    2011-12-01

    Full Text Available Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications. During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc. The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a food-induced dyspeptic symptoms (postprandial distress syndrome; and b epigastric pain (epigastric pain syndrome. These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a epigastric discomfort (as a category of severity or pain; b postprandial heaviness; and c early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn. All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the

  7. Methods for Functional Connectivity Analyses

    Science.gov (United States)

    2012-12-13

    motor , or hand motor function (green, red, or blue shading, respectively). Thus, this work produced the first comprehensive analysis of ECoG...Computer Engineering, University of Texas at El Paso , TX, USA 3Department of Neurology, Albany Medical College, Albany, NY, USA 4Department of Computer...Department of Health, Albany, NY, USA bDepartment of Electrical and Computer Engineering, University of Texas at El Paso , TX, USA cDepartment of Neurology

  8. Wigner functions defined with Laplace transform kernels.

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    Oh, Se Baek; Petruccelli, Jonathan C; Tian, Lei; Barbastathis, George

    2011-10-24

    We propose a new Wigner-type phase-space function using Laplace transform kernels--Laplace kernel Wigner function. Whereas momentum variables are real in the traditional Wigner function, the Laplace kernel Wigner function may have complex momentum variables. Due to the property of the Laplace transform, a broader range of signals can be represented in complex phase-space. We show that the Laplace kernel Wigner function exhibits similar properties in the marginals as the traditional Wigner function. As an example, we use the Laplace kernel Wigner function to analyze evanescent waves supported by surface plasmon polariton. © 2011 Optical Society of America

  9. Integrative proteomics and biochemical analyses define Ptc6p as the Saccharomyces cerevisiae pyruvate dehydrogenase phosphatase.

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    Guo, Xiao; Niemi, Natalie M; Coon, Joshua J; Pagliarini, David J

    2017-07-14

    The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue ∼50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S. cerevisiae has not been conclusively defined. Here, using comparative mitochondrial phosphoproteomics, analyses of protein-protein interactions by affinity enrichment-mass spectrometry, and in vitro biochemistry, we define Ptc6p as the primary PDC phosphatase in S. cerevisiae Our analyses further suggest additional substrates for related S. cerevisiae phosphatases and describe the overall phosphoproteomic changes that accompany mitochondrial respiratory dysfunction. In summary, our quantitative proteomics and biochemical analyses have identified Ptc6p as the primary-and likely sole- S. cerevisiae PDC phosphatase, closing a key knowledge gap about the regulation of yeast mitochondrial metabolism. Our findings highlight the power of integrative omics and biochemical analyses for annotating the functions of poorly characterized signaling proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Defining Functions of Danish Political Commentary

    DEFF Research Database (Denmark)

    Bengtsson, Mette

    2011-01-01

    In Denmark political commentary is still a relatively new phenomenon. This paper analyzes the metadiscourse in relation to political commentary to identify the different understandings that have coalesced around political commentary as a genre. I argue that people in different positions (e.......g. citizens, politicians, journalists, political editors, chief editors and political commentators themselves) emphasize different explanations for the rise of the genre and thereby functions of political commentary as part of an argumentative strategy favouring their own interests...

  11. DEFINE: A Service-Oriented Dynamically Enabling Function Model

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    Tan Wei-Yi

    2017-01-01

    In this paper, we introduce an innovative Dynamically Enable Function In Network Equipment (DEFINE to allow tenant get the network service quickly. First, DEFINE decouples an application into different functional components, and connects these function components in a reconfigurable method. Second, DEFINE provides a programmable interface to the third party, who can develop their own processing modules according to their own needs. To verify the effectiveness of this model, we set up an evaluating network with a FPGA-based OpenFlow switch prototype, and deployed several applications on it. Our results show that DEFINE has excellent flexibility and performance.

  12. Deletion and Gene Expression Analyses Define the Paxilline Biosynthetic Gene Cluster in Penicillium paxilli

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    Emily J. Parker

    2013-08-01

    Full Text Available The indole-diterpene paxilline is an abundant secondary metabolite synthesized by Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of which six have been previously confirmed to have a functional role in paxilline biosynthesis. A combination of bioinformatics, gene expression and targeted gene replacement analyses were used to define the boundaries of the PAX gene cluster. Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC, paxP and paxQ that were all required for paxilline production, with one additional gene, paxD, required for regular prenylation of the indole ring post paxilline synthesis. The two putative transcription factors, PP104 and PP105, were not co-regulated with the pax genes and based on targeted gene replacement, including the double knockout, did not have a role in paxilline production. The relationship of indole dimethylallyl transferases involved in prenylation of indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate clades, not supported by prenylation type (e.g., regular or reverse. This paper provides insight into the P. paxilli indole-diterpene locus and reviews the recent advances identified in paxilline biosynthesis.

  13. On the analytic continuation of functions defined by Legendre series

    International Nuclear Information System (INIS)

    Grinstein, F.F.

    1981-07-01

    An infinite diagonal sequence of Punctual Pade Approximants is considered for the approximate analytical continuation of a function defined by a formal Legendre series. The technique is tested in the case of two series with exactly known analytical sum: the generating function for Legendre polynomials and the Coulombian scattering amplitude. (author)

  14. Defining mental disorder. Exploring the 'natural function' approach

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    Varga Somogy

    2011-01-01

    Full Text Available Abstract Due to several socio-political factors, to many psychiatrists only a strictly objective definition of mental disorder, free of value components, seems really acceptable. In this paper, I will explore a variant of such an objectivist approach to defining metal disorder, natural function objectivism. Proponents of this approach make recourse to the notion of natural function in order to reach a value-free definition of mental disorder. The exploration of Christopher Boorse's 'biostatistical' account of natural function (1 will be followed an investigation of the 'hybrid naturalism' approach to natural functions by Jerome Wakefield (2. In the third part, I will explore two proposals that call into question the whole attempt to define mental disorder (3. I will conclude that while 'natural function objectivism' accounts fail to provide the backdrop for a reliable definition of mental disorder, there is no compelling reason to conclude that a definition cannot be achieved.

  15. Defining mental disorder. Exploring the 'natural function' approach.

    Science.gov (United States)

    Varga, Somogy

    2011-01-21

    Due to several socio-political factors, to many psychiatrists only a strictly objective definition of mental disorder, free of value components, seems really acceptable. In this paper, I will explore a variant of such an objectivist approach to defining metal disorder, natural function objectivism. Proponents of this approach make recourse to the notion of natural function in order to reach a value-free definition of mental disorder. The exploration of Christopher Boorse's 'biostatistical' account of natural function (1) will be followed an investigation of the 'hybrid naturalism' approach to natural functions by Jerome Wakefield (2). In the third part, I will explore two proposals that call into question the whole attempt to define mental disorder (3). I will conclude that while 'natural function objectivism' accounts fail to provide the backdrop for a reliable definition of mental disorder, there is no compelling reason to conclude that a definition cannot be achieved.

  16. Using greenhouse gas fluxes to define soil functional types

    Energy Technology Data Exchange (ETDEWEB)

    Petrakis, Sandra; Barba, Josep; Bond-Lamberty, Ben; Vargas, Rodrigo

    2017-12-04

    Soils provide key ecosystem services and directly control ecosystem functions; thus, there is a need to define the reference state of soil functionality. Most common functional classifications of ecosystems are vegetation-centered and neglect soil characteristics and processes. We propose Soil Functional Types (SFTs) as a conceptual approach to represent and describe the functionality of soils based on characteristics of their greenhouse gas (GHG) flux dynamics. We used automated measurements of CO2, CH4 and N2O in a forested area to define SFTs following a simple statistical framework. This study supports the hypothesis that SFTs provide additional insights on the spatial variability of soil functionality beyond information represented by commonly measured soil parameters (e.g., soil moisture, soil temperature, litter biomass). We discuss the implications of this framework at the plot-scale and the potential of this approach at larger scales. This approach is a first step to provide a framework to define SFTs, but a community effort is necessary to harmonize any global classification for soil functionality. A global application of the proposed SFT framework will only be possible if there is a community-wide effort to share data and create a global database of GHG emissions from soils.

  17. User defined function for transformation of ellipsoidal coordinates

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    Ganić Aleksandar

    2014-01-01

    Full Text Available The topographic plane of the Earth has irregular shape, and for the purpose of mathematical defining, it is to be approximated by rotational ellipsoid. As local geodetic datum, rotational ellipsoids of various sizes are used in the world. More widely usage of the GPS while performing surveying tasks has resulted in the need to define global geodetic datum in order to obtain the best approximation the entire Earth. For this purpose, geocentric rotational ellipsoid WGS84 was defined and the results of the GPS measurements are shown in relation to it. By applying the appropriate equations, the ellipsoidal coordinates are being transformed from WGS84 into the coordinates on the local rotational ellipsoid, i.e. on the view plane. The paper shows User Defined Function created for Excel, by which the coordinates in the territory of Belgrade are being transformed from WGS84 of rotational ellipsoid into the Gauss-Krüger projection plane.

  18. WEC Farm Functions: Defining the Behaviors of the Farm

    Energy Technology Data Exchange (ETDEWEB)

    Bull, Diana L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Costello, Ronan [Wave Venture Ltd, Penstraze (United Kingdom); Babarit, Aurelien [Ecole centrale de Nantes (France). Lab. of Research in Hydrodynamics, Energetics, and Atmospheric Environment (LHEEA); Malins, Robert Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kennedy, Ben [Wave Venture Ltd, Penstraze (United Kingdom); Neilson, Kim [Ramboll, Copenhagen (Denmark); Bittencourt, Claudio [DNV GL, London (United Kingdom); Roberts, Jesse D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Weber, Jochem [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-09-01

    Capabilities and functions are hierarchical structures (i.e. taxonomies) that are used in a systems engineering framework to identify complimentary requirements for the system: what the system must do to achieve what it must be. In the case of capabilities, the taxonomy embodies the list of characteristics that are desired, from the perspective of the stakeholders, for the system to be successful. In terms of the functions, the hierarchy represents the solution agnostic (i.e. independent of specific design embodiments) elements that are needed to meet the stakeholder requirements. This paper will focus on the development of the functions. The functions define the fundamental elements of the solution that must be provided in order to achieve the mission and deliver the capabilities. They identify the behaviors the farm must possess, i.e. the farm must be able to generate and deliver electricity from wave power. High-level functions are independent of the technology or design used to implement the function. However, detailed functions may begin to border on specific design choices. Hence a strong effort has been made to maintain functions that are design agnostic.

  19. Evolution of sequence-defined highly functionalized nucleic acid polymers

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    Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

    2018-03-01

    The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

  20. Defining functional DNA elements in the human genome

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    Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John A.; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

    2014-01-01

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. PMID:24753594

  1. 184 Compounding in Igala: Defining Criteria, Forms and Functions ...

    African Journals Online (AJOL)

    Ike Odimegwu

    West Benue-Congo language spoken in north central Nigeria. Defining ..... argues, in Ígálà, ọ́ma 'child', for instance, can stand in for the noun phrase 'ọ́ma óko' 'Oko's .... e.g. 'in Pawnee it is mainly body part words which are incorporated' (c.f. ...

  2. Defining and systematic analyses of aggregation indices to evaluate degree of calcium oxalate crystal aggregation

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    Chaiyarit, Sakdithep; Thongboonkerd, Visith

    2017-12-01

    Crystal aggregation is one of the most crucial steps in kidney stone pathogenesis. However, previous studies of crystal aggregation were rarely done and quantitative analysis of aggregation degree was handicapped by a lack of the standard measurement. We thus performed an in vitro assay to generate aggregation of calcium oxalate monohydrate (COM) crystals with various concentrations (25-800 µg/ml) in saturated aggregation buffer. The crystal aggregates were analyzed by microscopic examination, UV-visible spectrophotometry, and GraphPad Prism6 software to define a total of 12 aggregation indices (including number of aggregates, aggregated mass index, optical density, aggregation coefficient, span, number of aggregates at plateau time-point, aggregated area index, aggregated diameter index, aggregated symmetry index, time constant, half-life, and rate constant). The data showed linear correlation between crystal concentration and almost all of these indices, except only for rate constant. Among these, number of aggregates provided the greatest regression coefficient (r=0.997; pr=0.993; pr=‑0.993; pr=0.991; p<0.001 for both). These five indices are thus recommended as the most appropriate indices for quantitative analysis of COM crystal aggregation in vitro.

  3. On some strongly functions defined by α-open

    International Nuclear Information System (INIS)

    Kocaman, A.H.; Yuksel, S.; Acikgoz, A.

    2009-01-01

    In this paper is to introduce and investigate new classes of generalizations of non-continuous functions, obtain some of their properties and to hold decompositions of strong α-irresolute in topological spaces.

  4. Arithmetic convergent sequence space defined by modulus function

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    Taja Yaying

    2019-10-01

    Full Text Available The aim of this article is to introduce the sequence spaces $AC(f$ and $AS(f$ using arithmetic convergence and modulus function, and study algebraic and topological properties of this space, and certain inclusion results.

  5. Helicobacter Pylori Related Functional Dyspepsia in a Defined Malaysian Population

    OpenAIRE

    Nafeeza, M.I.; Isa, M.R.; Kudva, M.V.; Ishak, M.S.; Mazlam, M.Z.; Haron, A.; Najib, R.; Shahimi, M.M.

    2000-01-01

    The objective of the study was to determine the prevalence of H. pylori in functional dyspepsia among the three main races in Malaysia. Gastric antral biopsies from 233 (98 males, 135 females; age range: 17–75 years, mean age 39.5 years) patients attending the Universiti Kebangsaan Malaysia (UKM) gastroenterology clinic were assessed for the presence of H. pylori by culture and histology. About a third of the cases (79 of 233 (34%); 34 males, 45 females; mean age 42.6 yrs) were positive for H...

  6. Asymptotically double lacunry equivalent sequences defined by Orlicz functions

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    Ayhan Esi

    2014-04-01

    Full Text Available This paper presents the following definition which is natural combition of the definition for asymptotically equivalent and Orlicz function. The two nonnegative double sequences x=(x_{k,l} and y=(y_{k,l} are said to be M-asymptotically double equivalent to multiple L provided that for every ε>0, P-lim_{k,l}M(((|((x_{k,l}/(y_{k,l}-L|/ρ=0, for some ρ>0, (denoted by x∽y and simply M-asymptotically double equivalent if L=1. Also we give some new concepts related to this definition and some inclusion theorems.

  7. GenomeRunner web server: regulatory similarity and differences define the functional impact of SNP sets.

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    Dozmorov, Mikhail G; Cara, Lukas R; Giles, Cory B; Wren, Jonathan D

    2016-08-01

    The growing amount of regulatory data from the ENCODE, Roadmap Epigenomics and other consortia provides a wealth of opportunities to investigate the functional impact of single nucleotide polymorphisms (SNPs). Yet, given the large number of regulatory datasets, researchers are posed with a challenge of how to efficiently utilize them to interpret the functional impact of SNP sets. We developed the GenomeRunner web server to automate systematic statistical analysis of SNP sets within a regulatory context. Besides defining the functional impact of SNP sets, GenomeRunner implements novel regulatory similarity/differential analyses, and cell type-specific regulatory enrichment analysis. Validated against literature- and disease ontology-based approaches, analysis of 39 disease/trait-associated SNP sets demonstrated that the functional impact of SNP sets corresponds to known disease relationships. We identified a group of autoimmune diseases with SNPs distinctly enriched in the enhancers of T helper cell subpopulations, and demonstrated relevant cell type-specificity of the functional impact of other SNP sets. In summary, we show how systematic analysis of genomic data within a regulatory context can help interpreting the functional impact of SNP sets. GenomeRunner web server is freely available at http://www.integrativegenomics.org/ mikhail.dozmorov@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Functional enrichment analyses and construction of functional similarity networks with high confidence function prediction by PFP

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    Kihara Daisuke

    2010-05-01

    Full Text Available Abstract Background A new paradigm of biological investigation takes advantage of technologies that produce large high throughput datasets, including genome sequences, interactions of proteins, and gene expression. The ability of biologists to analyze and interpret such data relies on functional annotation of the included proteins, but even in highly characterized organisms many proteins can lack the functional evidence necessary to infer their biological relevance. Results Here we have applied high confidence function predictions from our automated prediction system, PFP, to three genome sequences, Escherichia coli, Saccharomyces cerevisiae, and Plasmodium falciparum (malaria. The number of annotated genes is increased by PFP to over 90% for all of the genomes. Using the large coverage of the function annotation, we introduced the functional similarity networks which represent the functional space of the proteomes. Four different functional similarity networks are constructed for each proteome, one each by considering similarity in a single Gene Ontology (GO category, i.e. Biological Process, Cellular Component, and Molecular Function, and another one by considering overall similarity with the funSim score. The functional similarity networks are shown to have higher modularity than the protein-protein interaction network. Moreover, the funSim score network is distinct from the single GO-score networks by showing a higher clustering degree exponent value and thus has a higher tendency to be hierarchical. In addition, examining function assignments to the protein-protein interaction network and local regions of genomes has identified numerous cases where subnetworks or local regions have functionally coherent proteins. These results will help interpreting interactions of proteins and gene orders in a genome. Several examples of both analyses are highlighted. Conclusion The analyses demonstrate that applying high confidence predictions from PFP

  9. Progressing From Initially Ambiguous Functional Analyses: Three Case Examples

    OpenAIRE

    Tiger, Jeffrey H.; Fisher, Wayne W.; Toussaint, Karen A.; Kodak, Tiffany

    2009-01-01

    Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or other...

  10. Empirically Defined Patterns of Executive Function Deficits in Schizophrenia and Their Relation to Everyday Functioning: A Person-Centered Approach

    Science.gov (United States)

    Iampietro, Mary; Giovannetti, Tania; Drabick, Deborah A. G.; Kessler, Rachel K.

    2013-01-01

    Executive function (EF) deficits in schizophrenia (SZ) are well documented, although much less is known about patterns of EF deficits and their association to differential impairments in everyday functioning. The present study empirically defined SZ groups based on measures of various EF abilities and then compared these EF groups on everyday action errors. Participants (n=45) completed various subtests from the Delis–Kaplan Executive Function System (D-KEFS) and the Naturalistic Action Test (NAT), a performance-based measure of everyday action that yields scores reflecting total errors and a range of different error types (e.g., omission, perseveration). Results of a latent class analysis revealed three distinct EF groups, characterized by (a) multiple EF deficits, (b) relatively spared EF, and (c) perseverative responding. Follow-up analyses revealed that the classes differed significantly on NAT total errors, total commission errors, and total perseveration errors; the two classes with EF impairment performed comparably on the NAT but performed worse than the class with relatively spared EF. In sum, people with SZ demonstrate variable patterns of EF deficits, and distinct aspects of these EF deficit patterns (i.e., poor mental control abilities) may be associated with everyday functioning capabilities. PMID:23035705

  11. Spatial analyses of benthic habitats to define coral reef ecosystem regions and potential biogeographic boundaries along a latitudinal gradient.

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    Brian K Walker

    Full Text Available Marine organism diversity typically attenuates latitudinally from tropical to colder climate regimes. Since the distribution of many marine species relates to certain habitats and depth regimes, mapping data provide valuable information in the absence of detailed ecological data that can be used to identify and spatially quantify smaller scale (10 s km coral reef ecosystem regions and potential physical biogeographic barriers. This study focused on the southeast Florida coast due to a recognized, but understudied, tropical to subtropical biogeographic gradient. GIS spatial analyses were conducted on recent, accurate, shallow-water (0-30 m benthic habitat maps to identify and quantify specific regions along the coast that were statistically distinct in the number and amount of major benthic habitat types. Habitat type and width were measured for 209 evenly-spaced cross-shelf transects. Evaluation of groupings from a cluster analysis at 75% similarity yielded five distinct regions. The number of benthic habitats and their area, width, distance from shore, distance from each other, and LIDAR depths were calculated in GIS and examined to determine regional statistical differences. The number of benthic habitats decreased with increasing latitude from 9 in the south to 4 in the north and many of the habitat metrics statistically differed between regions. Three potential biogeographic barriers were found at the Boca, Hillsboro, and Biscayne boundaries, where specific shallow-water habitats were absent further north; Middle Reef, Inner Reef, and oceanic seagrass beds respectively. The Bahamas Fault Zone boundary was also noted where changes in coastal morphologies occurred that could relate to subtle ecological changes. The analyses defined regions on a smaller scale more appropriate to regional management decisions, hence strengthening marine conservation planning with an objective, scientific foundation for decision making. They provide a framework

  12. A real-time transfer function analyser program for PFR

    International Nuclear Information System (INIS)

    McWilliam, D.

    1980-03-01

    A transfer function analyser software package has been produced which is believed to constitute a significant advance over others reported in the literature. The main advantages of the system are its operating speed, especially at low frequencies, which is due to its use of part-cycle integration and its high degree of interactive operator control. The driving sine wave, the return signals and the computed vector diagrams are displayed on TV type visual display units. Data output is by means of an incremental graph plotter or an IBM typewriter. (author)

  13. Diversity of Pol IV function is defined by mutations at the maize rmr7 locus.

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    Jennifer L Stonaker

    2009-11-01

    Full Text Available Mutations affecting the heritable maintenance of epigenetic states in maize identify multiple small RNA biogenesis factors including NRPD1, the largest subunit of the presumed maize Pol IV holoenzyme. Here we show that mutations defining the required to maintain repression7 locus identify a second RNA polymerase subunit related to Arabidopsis NRPD2a, the sole second largest subunit shared between Arabidopsis Pol IV and Pol V. A phylogenetic analysis shows that, in contrast to representative eudicots, grasses have retained duplicate loci capable of producing functional NRPD2-like proteins, which is indicative of increased RNA polymerase diversity in grasses relative to eudicots. Together with comparisons of rmr7 mutant plant phenotypes and their effects on the maintenance of epigenetic states with parallel analyses of NRPD1 defects, our results imply that maize utilizes multiple functional NRPD2-like proteins. Despite the observation that RMR7/NRPD2, like NRPD1, is required for the accumulation of most siRNAs, our data indicate that different Pol IV isoforms play distinct roles in the maintenance of meiotically-heritable epigenetic information in the grasses.

  14. DMPD: Structural and functional analyses of bacterial lipopolysaccharides. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12106784 Structural and functional analyses of bacterial lipopolysaccharides. Carof...html) (.csml) Show Structural and functional analyses of bacterial lipopolysaccharides. PubmedID 12106784 Title Structural and functi...onal analyses of bacterial lipopolysaccharides. Authors

  15. Evaluation of the divided attention condition during functional analyses.

    Science.gov (United States)

    Fahmie, Tara A; Iwata, Brian A; Harper, Jill M; Querim, Angie C

    2013-01-01

    A common condition included in most functional analyses (FAs) is the attention condition, in which the therapist ignores the client by engaging in a solitary activity (antecedent event) but delivers attention to the client contingent on problem behavior (consequent event). The divided attention condition is similar, except that the antecedent event consists of the therapist conversing with an adult confederate. We compared the typical and divided attention conditions to determine whether behavior in general (Study 1) and problem behavior in particular (Study 2) were more sensitive to one of the test conditions. Results showed that the divided attention condition resulted in faster acquisition or more efficient FA results for 2 of 9 subjects, suggesting that the divided attention condition could be considered a preferred condition when resources are available. © Society for the Experimental Analysis of Behavior.

  16. A New Class of Analytic Functions Defined by Using Salagean Operator

    Directory of Open Access Journals (Sweden)

    R. M. El-Ashwah

    2013-01-01

    Full Text Available We derive some results for a new class of analytic functions defined by using Salagean operator. We give some properties of functions in this class and obtain numerous sharp results including for example, coefficient estimates, distortion theorem, radii of star-likeness, convexity, close-to-convexity, extreme points, integral means inequalities, and partial sums of functions belonging to this class. Finally, we give an application involving certain fractional calculus operators that are also considered.

  17. Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ.

    Directory of Open Access Journals (Sweden)

    Till Adhikary

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are nuclear receptors with essential functions in lipid, glucose and energy homeostasis, cell differentiation, inflammation and metabolic disorders, and represent important drug targets. PPARs heterodimerize with retinoid X receptors (RXRs and can form transcriptional activator or repressor complexes at specific DNA elements (PPREs. It is believed that the decision between repression and activation is generally governed by a ligand-mediated switch. We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. Chromatin immunoprecipitation sequencing (ChIP-Seq of PPARβ/δ, H3K4me3 and RNA polymerase II enrichment sites combined with transcriptional profiling enabled the definition of 112 bona fide PPARβ/δ target genes showing either of three distinct types of transcriptional response: (I ligand-independent repression by PPARβ/δ; (II ligand-induced activation and/or derepression by PPARβ/δ; and (III ligand-independent activation by PPARβ/δ. These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. Our results also suggest that the type of transcriptional response by a given target gene is connected to the structure of its associated PPRE(s and the biological function of its encoded protein. These observations have important implications for understanding the regulatory PPAR network and PPARβ/δ ligand-based drugs.

  18. Functional differences between neurochemically defined populations of inhibitory interneurons in the rat spinal dorsal horn ?

    OpenAIRE

    Polg?r, Erika; Sardella, Thomas C.P.; Tiong, Sheena Y.X.; Locke, Samantha; Watanabe, Masahiko; Todd, Andrew J.

    2013-01-01

    In order to understand how nociceptive information is processed in the spinal dorsal horn we need to unravel the complex synaptic circuits involving interneurons, which constitute the vast majority of the neurons in laminae I?III. The main limitation has been the difficulty in defining functional populations among these cells. We have recently identified 4 non-overlapping classes of inhibitory interneuron, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase ...

  19. Functional Analysis in Public Schools: A Summary of 90 Functional Analyses

    Science.gov (United States)

    Mueller, Michael M.; Nkosi, Ajamu; Hine, Jeffrey F.

    2011-01-01

    Several review and epidemiological studies have been conducted over recent years to inform behavior analysts of functional analysis outcomes. None to date have closely examined demographic and clinical data for functional analyses conducted exclusively in public school settings. The current paper presents a data-based summary of 90 functional…

  20. Genetic analyses of the stability of executive functioning during childhood.

    NARCIS (Netherlands)

    Polderman, T.J.C.; Posthuma, D.; de Sonneville, L.M.J.; Stins, J.F.; Verhulst, F.C.; Boomsma, D.I.

    2007-01-01

    Executive functioning is an umbrella term for several related cognitive functions like selective- and sustained attention, working memory, and inhibition. Little is known about the stability of executive functioning during childhood. In this study the longitudinal stability of executive functioning

  1. Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation.

    Science.gov (United States)

    Zydziak, Nicolas; Konrad, Waldemar; Feist, Florian; Afonin, Sergii; Weidner, Steffen; Barner-Kowollik, Christopher

    2016-11-30

    Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy-combining sequential and modular concepts-enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain.

  2. Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

    Science.gov (United States)

    Beach, Adam; Leonov, Anna; Arlia-Ciommo, Anthony; Svistkova, Veronika; Lutchman, Vicky; Titorenko, Vladimir I.

    2015-01-01

    Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. PMID:25768339

  3. Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

    Directory of Open Access Journals (Sweden)

    Adam Beach

    2015-03-01

    Full Text Available Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research.

  4. Some double sequence spaces of interval numbers defined by Orlicz function

    Directory of Open Access Journals (Sweden)

    Ayhan Esi

    2014-10-01

    Full Text Available In this paper we introduce some interval valued double sequence spaces defined by Orlicz function and study different properties of these spaces like inclusion relations, solidity, etc. We establish some inclusion relations among them. Also we introduce the concept of double statistical convergence for interval number sequences and give an inclusion relation between interval valued double sequence spaces.

  5. A Compilation of MATLAB Scripts and Functions for MACGMC Analyses

    Science.gov (United States)

    Murthy, Pappu L. N.; Bednarcyk, Brett A.; Mital, Subodh K.

    2017-01-01

    The primary aim of the current effort is to provide scripts that automate many of the repetitive pre- and post-processing tasks associated with composite materials analyses using the Micromechanics Analysis Code with the Generalized Method of Cells. This document consists of a compilation of hundreds of scripts that were developed in MATLAB (The Mathworks, Inc., Natick, MA) programming language and consolidated into 16 MATLAB functions. (MACGMC). MACGMC is a composite material and laminate analysis software code developed at NASA Glenn Research Center. The software package has been built around the generalized method of cells (GMC) family of micromechanics theories. The computer code is developed with a user-friendly framework, along with a library of local inelastic, damage, and failure models. Further, application of simulated thermo-mechanical loading, generation of output results, and selection of architectures to represent the composite material have been automated to increase the user friendliness, as well as to make it more robust in terms of input preparation and code execution. Finally, classical lamination theory has been implemented within the software, wherein GMC is used to model the composite material response of each ply. Thus, the full range of GMC composite material capabilities is available for analysis of arbitrary laminate configurations as well. The pre-processing tasks include generation of a multitude of different repeating unit cells (RUCs) for CMCs and PMCs, visualization of RUCs from MACGMC input and output files and generation of the RUC section of a MACGMC input file. The post-processing tasks include visualization of the predicted composite response, such as local stress and strain contours, damage initiation and progression, stress-strain behavior, and fatigue response. In addition to the above, several miscellaneous scripts have been developed that can be used to perform repeated Monte-Carlo simulations to enable probabilistic

  6. Between morphology and function: How syntactic centers of the Beijing city are defined

    Directory of Open Access Journals (Sweden)

    Tao Yang

    2015-12-01

    Full Text Available The application of big data provides a new angle of view on investigating whether, and if so, how to define the urban center through analyzing urban spatial morphology intrinsically interacts with its functions. This article, using empirical research of the Beijing city, first seeking to explore spatial configuration-the complex relation between any pair of individual spaces regarding other contextual spaces – of urban network collected from Baidu. And then, focusing on conducting a statistical correlation between the configurational patterns of urban network and the aggregation patterns of functions. Based on the different patterns of aggregation or dispersion of those functions we discussed, as well as the multi-scale syntactic location choice underlying those patterns, it then can be identified four types of centers in the Beijing city, which may be called active center, ordinary center, brand centers and specified center, as well as the extent to which spatial layout influences functional distribution.

  7. Individual-based analyses reveal limited functional overlap in a coral reef fish community.

    Science.gov (United States)

    Brandl, Simon J; Bellwood, David R

    2014-05-01

    Detailed knowledge of a species' functional niche is crucial for the study of ecological communities and processes. The extent of niche overlap, functional redundancy and functional complementarity is of particular importance if we are to understand ecosystem processes and their vulnerability to disturbances. Coral reefs are among the most threatened marine systems, and anthropogenic activity is changing the functional composition of reefs. The loss of herbivorous fishes is particularly concerning as the removal of algae is crucial for the growth and survival of corals. Yet, the foraging patterns of the various herbivorous fish species are poorly understood. Using a multidimensional framework, we present novel individual-based analyses of species' realized functional niches, which we apply to a herbivorous coral reef fish community. In calculating niche volumes for 21 species, based on their microhabitat utilization patterns during foraging, and computing functional overlaps, we provide a measurement of functional redundancy or complementarity. Complementarity is the inverse of redundancy and is defined as less than 50% overlap in niche volumes. The analyses reveal extensive complementarity with an average functional overlap of just 15.2%. Furthermore, the analyses divide herbivorous reef fishes into two broad groups. The first group (predominantly surgeonfishes and parrotfishes) comprises species feeding on exposed surfaces and predominantly open reef matrix or sandy substrata, resulting in small niche volumes and extensive complementarity. In contrast, the second group consists of species (predominantly rabbitfishes) that feed over a wider range of microhabitats, penetrating the reef matrix to exploit concealed surfaces of various substratum types. These species show high variation among individuals, leading to large niche volumes, more overlap and less complementarity. These results may have crucial consequences for our understanding of herbivorous processes on

  8. Analyses of 123 Peripheral Human Immune Cell Subsets: Defining Differences with Age and between Healthy Donors and Cancer Patients Not Detected in Analysis of Standard Immune Cell Types

    Directory of Open Access Journals (Sweden)

    Lauren M. Lepone

    2016-03-01

    Full Text Available Recent advances in human immunology have led to the identification of novel immune cell subsets and the biological function of many of these subsets has now been identified. The recent US Food and Drug Administration approval of several immunotherapeutics for the treatment of a variety of cancer types and the results of ongoing immunotherapy clinical studies requires a more thorough interrogation of the immune system. We report here the use of flow cytometry-based analyses to identify 123 immune cell subsets of peripheral blood mononuclear cells. The use of these panels defines multiple differences in younger (< 40 years vs. older (≥ 40 years individuals and between aged-matched apparently healthy individuals and metastatic cancer patients, aspects not seen in the analysis of the following standard immune cell types: CD8, CD4, natural killer, natural killer-T, regulatory T, myeloid derived suppressor cells, conventional dendritic cells (DCs, plasmacytoid DCs and B cells. The use of these panels identifying 123 immune cell subsets may aid in the identification of patients who may benefit from immunotherapy, either prior to therapy or early in the immunotherapeutic regimen, for the treatment of cancer or other chronic or infectious diseases.

  9. Defining reference sequences for Nocardia species by similarity and clustering analyses of 16S rRNA gene sequence data.

    Directory of Open Access Journals (Sweden)

    Manal Helal

    Full Text Available BACKGROUND: The intra- and inter-species genetic diversity of bacteria and the absence of 'reference', or the most representative, sequences of individual species present a significant challenge for sequence-based identification. The aims of this study were to determine the utility, and compare the performance of several clustering and classification algorithms to identify the species of 364 sequences of 16S rRNA gene with a defined species in GenBank, and 110 sequences of 16S rRNA gene with no defined species, all within the genus Nocardia. METHODS: A total of 364 16S rRNA gene sequences of Nocardia species were studied. In addition, 110 16S rRNA gene sequences assigned only to the Nocardia genus level at the time of submission to GenBank were used for machine learning classification experiments. Different clustering algorithms were compared with a novel algorithm or the linear mapping (LM of the distance matrix. Principal Components Analysis was used for the dimensionality reduction and visualization. RESULTS: The LM algorithm achieved the highest performance and classified the set of 364 16S rRNA sequences into 80 clusters, the majority of which (83.52% corresponded with the original species. The most representative 16S rRNA sequences for individual Nocardia species have been identified as 'centroids' in respective clusters from which the distances to all other sequences were minimized; 110 16S rRNA gene sequences with identifications recorded only at the genus level were classified using machine learning methods. Simple kNN machine learning demonstrated the highest performance and classified Nocardia species sequences with an accuracy of 92.7% and a mean frequency of 0.578. CONCLUSION: The identification of centroids of 16S rRNA gene sequence clusters using novel distance matrix clustering enables the identification of the most representative sequences for each individual species of Nocardia and allows the quantitation of inter- and intra

  10. User-defined functions in the Arden Syntax: An extension proposal.

    Science.gov (United States)

    Karadimas, Harry; Ebrahiminia, Vahid; Lepage, Eric

    2015-12-11

    The Arden Syntax is a knowledge-encoding standard, started in 1989, and now in its 10th revision, maintained by the health level seven (HL7) organization. It has constructs borrowed from several language concepts that were available at that time (mainly the HELP hospital information system and the Regenstrief medical record system (RMRS), but also the Pascal language, functional languages and the data structure of frames, used in artificial intelligence). The syntax has a rationale for its constructs, and has restrictions that follow this rationale. The main goal of the Standard is to promote knowledge sharing, by avoiding the complexity of traditional programs, so that a medical logic module (MLM) written in the Arden Syntax can remain shareable and understandable across institutions. One of the restrictions of the syntax is that you cannot define your own functions and subroutines inside an MLM. An MLM can, however, call another MLM, where this MLM will serve as a function. This will add an additional dependency between MLMs, a known criticism of the Arden Syntax knowledge model. This article explains why we believe the Arden Syntax would benefit from a construct for user-defined functions, discusses the need, the benefits and the limitations of such a construct. We used the recent grammar of the Arden Syntax v.2.10, and both the Arden Syntax standard document and the Arden Syntax Rationale article as guidelines. We gradually introduced production rules to the grammar. We used the CUP parsing tool to verify that no ambiguities were detected. A new grammar was produced, that supports user-defined functions. 22 production rules were added to the grammar. A parser was built using the CUP parsing tool. A few examples are given to illustrate the concepts. All examples were parsed correctly. It is possible to add user-defined functions to the Arden Syntax in a way that remains coherent with the standard. We believe that this enhances the readability and the robustness

  11. Model for defining the level of implementation of the management functions in small enterprises

    Directory of Open Access Journals (Sweden)

    Dragan Mišetić

    2001-01-01

    Full Text Available Small enterprises, based on private ownership and entrepreneurial capability, represent, for the majority of the scientific and professional public, the prime movers of economic growth, both in developed market economies and in the economies of countries in transition. At the same time, various studies show that the main reason for the bankruptcy of many small enterprises (more than 90% can be found in weak management, i.e. unacquaintance with management functions (planning, organization, human resources management, leading and control and with the need of implementing those functions in practice. Although it is not easy to define the ingredients of the recipe for success or to define precisely the importance of different elements, and regardless of the fact that many authors think that the management theory for large enterprises is inapplicable for the small ones, we all agree that the owner/manager and his implementation of the management theory has a decisive influence on small enterprises in modern economic circumstances. Therefore, the author of this work is hereby representing the model, which defines the level of implementation of management functions in small enterprises, as well as three systems/levels (danger, risk, progress in which small enterprises may find themselves. After the level of implementation of the management function is identified, it is possible to undertake some corrective actions, which will remove the found failures. While choosing the variables of the model, the author took into consideration specific features of a small enterprise, as well as specific features of its owner/manager.

  12. Alzheimer’s disease: How metal ions define β-amyloid function

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2017-01-01

    focuses on the essential coordination chemistry and biochemistry that relate transition metal ions iron, copper, and zinc to β-amyloid (Aβ) and most likely define the peptide's roles in neurons. The metal-Aβ interactions have elements of both gain of toxic function, as usually considered, but also loss......Alzheimer’s disease is increasingly recognized to be linked to the function and status of metal ions, and recently, the amyloid hypothesis has been strongly intertwined with the metal ion hypothesis; in fact, these two hypotheses fit well together and are not mutually contradictory. This review...... of natural functions, as emphasized in this review. Both these aspects and their relationships are discussed and their implications for future therapeutic strategies are outlined....

  13. Gene Discovery and Functional Analyses in the Model Plant Arabidopsis

    DEFF Research Database (Denmark)

    Feng, Cai-ping; Mundy, J.

    2006-01-01

    The present mini-review describes newer methods and strategies, including transposon and T-DNA insertions, TILLING, Deleteagene, and RNA interference, to functionally analyze genes of interest in the model plant Arabidopsis. The relative advantages and disadvantages of the systems are also discus...

  14. Computer assisted functional analysis. Computer gestuetzte funktionelle Analyse

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, H A.E.; Roesler, H

    1982-01-01

    The latest developments in computer-assisted functional analysis (CFA) in nuclear medicine are presented in about 250 papers of the 19th international annual meeting of the Society of Nuclear Medicine (Bern, September 1981). Apart from the mathematical and instrumental aspects of CFA, computerized emission tomography is given particular attention. Advances in nuclear medical diagnosis in the fields of radiopharmaceuticals, cardiology, angiology, neurology, ophthalmology, pulmonology, gastroenterology, nephrology, endocrinology, oncology and osteology are discussed.

  15. Plant ion channels: gene families, physiology, and functional genomics analyses.

    Science.gov (United States)

    Ward, John M; Mäser, Pascal; Schroeder, Julian I

    2009-01-01

    Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

  16. Integrative transcriptome and proteome analyses define marked differences between Neospora caninum isolates throughout the tachyzoite lytic cycle.

    Science.gov (United States)

    Horcajo, P; Xia, D; Randle, N; Collantes-Fernández, E; Wastling, J; Ortega-Mora, L M; Regidor-Cerrillo, J

    2017-11-14

    Neospora caninum is one of the main causes of transmissible abortion in cattle. Intraspecific variations in virulence have been widely shown among N. caninum isolates. However, the molecular basis governing such variability have not been elucidated to date. In this study label free LC-MS/MS was used to investigate proteome differences between the high virulence isolate Nc-Spain7 and the low virulence isolate Nc-Spain1H throughout the tachyzoite lytic cycle. The results showed greater differences in the abundance of proteins at invasion and egress with 77 and 62 proteins, respectively. During parasite replication, only 19 proteins were differentially abundant between isolates. The microneme protein repertoire involved in parasite invasion and egress was more abundant in the Nc-Spain1H isolate, which displays a lower invasion rate. Rhoptry and dense granule proteins, proteins related to metabolism and stress responses also showed differential abundances between isolates. Comparative RNA-Seq analyses during tachyzoite egress were also performed, revealing an expression profile of genes associated with the bradyzoite stage in the low virulence Nc-Spain1H isolate. The differences in proteome and RNA expression profiles between these two isolates reveal interesting insights into likely mechanisms involved in specific phenotypic traits and virulence in N. caninum. The molecular basis that governs biological variability in N. caninum and the pathogenesis of neosporosis has not been well-established yet. This is the first study in which high throughput technology of LC-MS/MS and RNA-Seq is used to investigate differences in the proteome and transcriptome between two well-characterized isolates. Both isolates displayed different proteomes throughout the lytic cycle and the transcriptomes also showed marked variations but were inconsistent with the proteome results. However, both datasets identified a pre-bradyzoite status of the low virulence isolate Nc-Spain1H. This study

  17. Generation of functional inhibitory synapses incorporating defined combinations of GABA(A or glycine receptor subunits

    Directory of Open Access Journals (Sweden)

    Christine Laura Dixon

    2015-12-01

    Full Text Available Fast inhibitory neurotransmission in the brain is mediated by wide range of GABAA receptor (GABAAR and glycine receptor (GlyR isoforms, each with different physiological and pharmacological properties. Because multiple isoforms are expressed simultaneously in most neurons, it is difficult to define the properties of inhibitory postsynaptic currents mediated by individual isoforms in vivo. Although recombinant expression systems permit the expression of individual isoforms in isolation, they require exogenous agonist application which cannot mimic the dynamic neurotransmitter profile characteristic of native synapses. We describe a neuron-HEK293 cell co-culture technique for generating inhibitory synapses incorporating defined combinations of GABAAR or GlyR subunits. Primary neuronal cultures, prepared from embryonic rat cerebral cortex or spinal cord, are used to provide presynaptic GABAergic and glycinergic terminals, respectively. When the cultures are mature, HEK293 cells expressing the subunits of interest plus neuroligin 2A are plated onto the neurons, which rapidly form synapses onto HEK293 cells. Patch clamp electrophysiology is then used to analyze the physiological and pharmacological properties of the inhibitory postsynaptic currents mediated by the recombinant receptors. The method is suitable for investigating the kinetic properties or the effects of drugs on inhibitory postsynaptic currents mediated by defined GABAAR or GlyR isoforms of interest, the effects of hereditary disease mutations on the formation and function of both types of synapses, and synaptogenesis and synaptic clustering mechanisms. The entire cell preparation procedure takes 2 – 5 weeks.

  18. Neurocognitive function in HIV-infected patients: comparison of two methods to define impairment.

    Directory of Open Access Journals (Sweden)

    Alejandro Arenas-Pinto

    Full Text Available To compare two definitions of neurocognitive impairment (NCI in a large clinical trial of effectively-treated HIV-infected adults at baseline.Hopkins Verbal Learning test-Revised (HVLT-R, Colour Trail (CTT and Grooved Pegboard (GPT tests were applied exploring five cognitive domains. Raw scores were transformed into Z-scores and NCI defined as summary NPZ-5 score one standard deviation below the mean of the normative dataset (i.e. <-1SD or Z-scores <-1SD in at least two individual domains (categorical scale. Principal component analysis (PCA was performed to explore the contribution of individual tests to the total variance.Mean NPZ-5 score was -0.72 (SD 0.98 and 178/548 (32% participants had NPZ-5 scores <-1SD. When impairment was defined as <-1SD in at least two individual tests, 283 (52% patients were impaired. Strong correlations between the two components of the HVLT-R test (learning/recall (r = 0.73, and the CTT and (attention/executive functioning (r = 0.66 were observed. PCA showed a clustering with three components accounting for 88% of the total variance. When patients who scored <-1SD only in two correlated tests were considered as not impaired, prevalence of NCI was 43%. When correlated test scores were averaged, 36% of participants had NPZ-3 scores <-1SD and 32% underperformed in at least two individual tests.Controlling for differential contribution of individual test-scores on the overall performance and the level of correlation between components of the test battery used appear to be important when testing cognitive function. These two factors are likely to affect both summary scores and categorical scales in defining cognitive impairment.EUDRACT: 2007-006448-23 and ISRCTN04857074.

  19. Performance verification of network function virtualization in software defined optical transport networks

    Science.gov (United States)

    Zhao, Yongli; Hu, Liyazhou; Wang, Wei; Li, Yajie; Zhang, Jie

    2017-01-01

    With the continuous opening of resource acquisition and application, there are a large variety of network hardware appliances deployed as the communication infrastructure. To lunch a new network application always implies to replace the obsolete devices and needs the related space and power to accommodate it, which will increase the energy and capital investment. Network function virtualization1 (NFV) aims to address these problems by consolidating many network equipment onto industry standard elements such as servers, switches and storage. Many types of IT resources have been deployed to run Virtual Network Functions (vNFs), such as virtual switches and routers. Then how to deploy NFV in optical transport networks is a of great importance problem. This paper focuses on this problem, and gives an implementation architecture of NFV-enabled optical transport networks based on Software Defined Optical Networking (SDON) with the procedure of vNFs call and return. Especially, an implementation solution of NFV-enabled optical transport node is designed, and a parallel processing method for NFV-enabled OTN nodes is proposed. To verify the performance of NFV-enabled SDON, the protocol interaction procedures of control function virtualization and node function virtualization are demonstrated on SDON testbed. Finally, the benefits and challenges of the parallel processing method for NFV-enabled OTN nodes are simulated and analyzed.

  20. The C. elegans Connectome Consists of Homogenous Circuits with Defined Functional Roles.

    Directory of Open Access Journals (Sweden)

    Aharon Azulay

    2016-09-01

    Full Text Available A major goal of systems neuroscience is to decipher the structure-function relationship in neural networks. Here we study network functionality in light of the common-neighbor-rule (CNR in which a pair of neurons is more likely to be connected the more common neighbors it shares. Focusing on the fully-mapped neural network of C. elegans worms, we establish that the CNR is an emerging property in this connectome. Moreover, sets of common neighbors form homogenous structures that appear in defined layers of the network. Simulations of signal propagation reveal their potential functional roles: signal amplification and short-term memory at the sensory/inter-neuron layer, and synchronized activity at the motoneuron layer supporting coordinated movement. A coarse-grained view of the neural network based on homogenous connected sets alone reveals a simple modular network architecture that is intuitive to understand. These findings provide a novel framework for analyzing larger, more complex, connectomes once these become available.

  1. Different methods to define utility functions yield similar results but engage different neural processes

    Directory of Open Access Journals (Sweden)

    Marcus Heldmann

    2009-10-01

    Full Text Available Although the concept of utility is fundamental to many economic theories, up to now a generally accepted method determining a subject’s utility function is not available. We investigated two methods that are used in economic sciences for describing utility functions by using response-locked event-related potentials in order to assess their neural underpinnings. For defining the certainty equivalent (CE, we used a lottery game with probabilities to win p=0.5, for identifying the subjects’ utility functions directly a standard bisection task was applied. Although the lottery tasks’ payoffs were only hypothetical, a pronounced negativity was observed resembling the error related negativity (ERN previously described in action monitoring research, but this occurred only for choices far away from the indifference point between money and lottery. By contrast, the bisection task failed to evoke an ERN irrespective of the responses’ correctness. Based on these findings we are reasoning that only decisions made in the lottery task achieved a level of subjective relevance that activates cognitive-emotional monitoring. In terms of economic sciences, our findings support the view that the bisection method is unaffected by any kind of probability valuation or other parameters related to risk and in combination with the lottery task can, therefore, be used to differentiate between payoff and probability valuation.

  2. Correlation of Theory and Function in Well-Defined Bimetallic Electrocatalysts - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Crooks, Richard M.

    2014-06-05

    The objective of this research proposal was to correlate the structure of nanoparticles that are comprised of ~100-200 atoms to their electrocatalytic function. This objective was based on the growing body of evidence suggesting that catalytic properties can be tailored through controlled synthesis of nanoparticles. What has been missing from many of these studies, and what we are contributing, is a model catalyst that is sufficiently small, structurally well-defined, and well-characterized that its function can be directly predicted by theory. Specifically, our work seeks to develop a fundamental and detailed understanding of the relationship between the structure of nanoscopic oxygen-reduction catalysts and their function. We assembled a team with expertise in theory, synthesis, and advanced characterization methods to address the primary objective of this project. We anticipated the outcomes of the study to be: (1) a better theoretical understanding of how nanoparticle structure affects catalytic properties; (2) the development of advanced, in-situ and ex-situ, atomic-scale characterization methods that are appropriate for particles containing about 100 atoms; and (3) improved synthetic methods that produce unique nanoparticle structures that can be used to test theoretical predictions. During the project period, we have made excellent progress on all three fronts.

  3. SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.

    Science.gov (United States)

    Muhar, Matthias; Ebert, Anja; Neumann, Tobias; Umkehrer, Christian; Jude, Julian; Wieshofer, Corinna; Rescheneder, Philipp; Lipp, Jesse J; Herzog, Veronika A; Reichholf, Brian; Cisneros, David A; Hoffmann, Thomas; Schlapansky, Moritz F; Bhat, Pooja; von Haeseler, Arndt; Köcher, Thomas; Obenauf, Anna C; Popow, Johannes; Ameres, Stefan L; Zuber, Johannes

    2018-05-18

    Defining direct targets of transcription factors and regulatory pathways is key to understanding their roles in physiology and disease. We combined SLAM-seq [thiol(SH)-linked alkylation for the metabolic sequencing of RNA], a method for direct quantification of newly synthesized messenger RNAs (mRNAs), with pharmacological and chemical-genetic perturbation in order to define regulatory functions of two transcriptional hubs in cancer, BRD4 and MYC, and to interrogate direct responses to BET bromodomain inhibitors (BETis). We found that BRD4 acts as general coactivator of RNA polymerase II-dependent transcription, which is broadly repressed upon high-dose BETi treatment. At doses triggering selective effects in leukemia, BETis deregulate a small set of hypersensitive targets including MYC. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator controlling metabolic processes such as ribosome biogenesis and de novo purine synthesis. Our study establishes a simple and scalable strategy to identify direct transcriptional targets of any gene or pathway. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. Self-defining future projections: exploring the identity function of thinking about the future.

    Science.gov (United States)

    D'Argembeau, Arnaud; Lardi, Claudia; Van der Linden, Martial

    2012-01-01

    The act of projecting oneself into meaningful future events may significantly contribute to a person's sense of self and identity. Yet if the role of memories, in particular self-defining memories (SDMs), in grounding the self is now well established, the identity function of anticipated future events has received comparatively little attention. This article introduces the construct of self-defining future projection (SDFP) to address this issue. Two studies show that people can readily identify significant future events that they frequently think about and that convey core information about who they are as individuals. Furthermore, a person's particular style of constructing SDMs is similarly manifested in SDFPs, suggesting that both types of events can be used to ground the self. Notably, people who display a stronger tendency to extract meaning from their past experiences also reflect more about the potential implications of imagined future events. The results further demonstrate that SDMs and SDFPs both give rise to a strong sense of personal continuity over time and are meaningfully related to self-esteem. Together these findings lend support to the idea that a person's sense of self and identity is in part nourished by the anticipation of significant future events.

  5. A Constrained Genetic Algorithm with Adaptively Defined Fitness Function in MRS Quantification

    Science.gov (United States)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; Graveron-Demilly, D.; van Ormondt, D.

    MRS Signal quantification is a rather involved procedure and has attracted the interest of the medical engineering community, regarding the development of computationally efficient methodologies. Significant contributions based on Computational Intelligence tools, such as Neural Networks (NNs), demonstrated a good performance but not without drawbacks already discussed by the authors. On the other hand preliminary application of Genetic Algorithms (GA) has already been reported in the literature by the authors regarding the peak detection problem encountered in MRS quantification using the Voigt line shape model. This paper investigates a novel constrained genetic algorithm involving a generic and adaptively defined fitness function which extends the simple genetic algorithm methodology in case of noisy signals. The applicability of this new algorithm is scrutinized through experimentation in artificial MRS signals interleaved with noise, regarding its signal fitting capabilities. Although extensive experiments with real world MRS signals are necessary, the herein shown performance illustrates the method's potential to be established as a generic MRS metabolites quantification procedure.

  6. On calculating double logarithmical asymptotics of vertex functions defined on the mass shell

    International Nuclear Information System (INIS)

    Belokurov, V.V.; Usyukina, N.I.

    1981-01-01

    The essence of the calculation method of double logarithmical asymptotics of vertex functions defined on the mass shell is presented. Using the method the asymptotics of the form-factor of electron is calculated. The ladder and cross-ladder diagrams are asymptotically considerable in every order of the perturbation theory. The way in which the asymptotics of the 4-order diagrams is calculated has been shown. The diagrams of this order and reduction procedures for them are given in a graphic form. The photon mass μ 2 not equal to 0 plays the role of a regulator, removing infrared divergencies. The double logarithmical asymptotics of the form-factor of electron on the mass shell is calculated rigorously in an arbitrary order of the perturbation theory [ru

  7. In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System.

    Science.gov (United States)

    Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

    2014-01-01

    In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy.

  8. CAD/CAM splints for the functional and esthetic evaluation of newly defined occlusal dimensions.

    Science.gov (United States)

    Edelhoff, Daniel; Schweiger, Josef; Prandtner, Otto; Trimpl, Johannes; Stimmelmayr, Michael; Güth, Jan-Frederik

    2017-01-01

    Pretreatment with occlusal splints is a crucial step in a structured treatment approach for a complex rehabilitation that changes the vertical dimension of occlusion. Meticulous patient compliance is one of the essential prerequisites for overall treatment success. However, patient compliance is all too often insufficient due to esthetic, phonetic, and functional limitations when using conventional occlusal splints in one arch. Modern production technologies now allow the use of tooth-colored occlusal splints made of polycarbonate, whose quality and material properties are quite distinct from those of conventionally manufactured splints made of transparent polymethyl methacrylate (PMMA). These materials, produced under standardized polymerization conditions, are extremely homogenous, which provides benefits such as a greater accuracy of fit by eliminating the polymerization shrinkage, greater long-term stability of shapes and shades, better biocompatibility, less wear, and a more favorable esthetic appearance. In addition, tooth-colored polycarbonate splints can be fabricated very thin without significantly increasing the fracture risk, thanks to the flexibility of the material. The improved wearing comfort combined with acceptable esthetics result in significantly improved patient compliance in terms of a "23-hour splint." By providing separate splints for the maxilla and mandible in the case of major alterations of the vertical dimension of occlusion, the esthetic and functional aspects defined by the wax-up can be completely transferred to the removable splints for a "test drive" by the patient, reversibly, and under realistic conditions. This dual-splint approach additionally facilitates segmental transfer into the definitive restoration.

  9. Direct conversion of human fibroblasts into functional osteoblasts by defined factors.

    Science.gov (United States)

    Yamamoto, Kenta; Kishida, Tsunao; Sato, Yoshiki; Nishioka, Keisuke; Ejima, Akika; Fujiwara, Hiroyoshi; Kubo, Toshikazu; Yamamoto, Toshiro; Kanamura, Narisato; Mazda, Osam

    2015-05-12

    Osteoblasts produce calcified bone matrix and contribute to bone formation and remodeling. In this study, we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some defined factors and culturing in osteogenic medium. Osteoblast-specific transcription factors, Runt-related transcription factor 2 (Runx2), and Osterix, in combination with Octamer-binding transcription factor 3/4 (Oct4) and L-Myc (RXOL) transduction, converted ∼ 80% of the fibroblasts into osteocalcin-producing cells. The directly converted osteoblasts (dOBs) induced by RXOL displayed a similar gene expression profile as normal human osteoblasts and contributed to bone repair after transplantation into immunodeficient mice at artificial bone defect lesions. The dOBs expressed endogenous Runx2 and Osterix, and did not require continuous expression of the exogenous genes to maintain their phenotype. Another combination, Oct4 plus L-Myc (OL), also induced fibroblasts to produce bone matrix, but the OL-transduced cells did not express Osterix and exhibited a more distant gene expression profile to osteoblasts compared with RXOL-transduced cells. These findings strongly suggest successful direct reprogramming of fibroblasts into functional osteoblasts by RXOL, a technology that may provide bone regeneration therapy against bone disorders.

  10. Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures.

    Science.gov (United States)

    Bohlen, Christopher J; Bennett, F Chris; Tucker, Andrew F; Collins, Hannah Y; Mulinyawe, Sara B; Barres, Ben A

    2017-05-17

    Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. RYBP and Cbx7 Define Specific Biological Functions of Polycomb Complexes in Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Lluis Morey

    2013-01-01

    Full Text Available The Polycomb repressive complex 1 (PRC1 is required for decisions of stem cell fate. In mouse embryonic stem cells (ESCs, two major variations of PRC1 complex, defined by the mutually exclusive presence of Cbx7 or RYBP, have been identified. Here, we show that although the genomic localization of the Cbx7- and RYBP-containing PRC1 complexes overlaps in certain genes, it can also be mutually exclusive. At the molecular level, Cbx7 is necessary for recruitment of Ring1B to chromatin, whereas RYBP enhances the PRC1 enzymatic activity. Genes occupied by RYBP show lower levels of Ring1B and H2AK119ub and are consequently more highly transcribed than those bound by Cbx7. At the functional level, we show that genes occupied by RYBP are primarily involved in the regulation of metabolism and cell-cycle progression, whereas those bound by Cbx7 predominantly control early-lineage commitment of ESCs. Altogether, our results indicate that different PRC1 subtypes establish a complex pattern of gene regulation that regulates common and nonoverlapping aspects of ESC pluripotency and differentiation.

  12. Evaluation of an Empirical Reservoir Shape Function to Define Sediment Distributions in Small Reservoirs

    Directory of Open Access Journals (Sweden)

    Bogusław Michalec

    2015-08-01

    Full Text Available Understanding and defining the spatial distribution of sediment deposited in reservoirs is essential not only at the design stage but also during the operation. The majority of research concerns the distribution of sediment deposition in medium and large water reservoirs. Most empirical methods do not provide satisfactory results when applied to the determination of sediment deposition in small reservoirs. Small reservoir’s volumes do not exceed 5 × 106 m3 and their capacity-inflow ratio is less than 10%. Long-term silting measurements of three small reservoirs were used to evaluate the method described by Rahmanian and Banihashemi for predicting sediment distributions in small reservoirs. Rahmanian and Banihashemi stated that their model of distribution of sediment deposition in water reservoir works well for a long duration operation. In the presented study, the silting rate was used in order to determine the long duration operation. Silting rate is a quotient of volume of the sediment deposited in the reservoir and its original volume. It was stated that when the silting rate had reached 50%, the sediment deposition in the reservoir may be described by an empirical reservoir depth shape function (RDSF.

  13. Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

    International Nuclear Information System (INIS)

    Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

    2004-01-01

    A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

  14. Associations of anatomical measures from MRI with radiographically defined knee osteoarthritis score, pain, and physical functioning.

    Science.gov (United States)

    Sowers, Maryfran; Karvonen-Gutierrez, Carrie A; Jacobson, Jon A; Jiang, Yebin; Yosef, Matheos

    2011-02-02

    The prevalence of knee osteoarthritis is traditionally based on radiographic findings, but magnetic resonance imaging is now being used to provide better visualization of bone, cartilage, and soft tissues as well as the patellar compartment. The goal of this study was to estimate the prevalences of knee features defined on magnetic resonance imaging in a population and to relate these abnormalities to knee osteoarthritis severity scores based on radiographic findings, physical functioning, and reported knee pain in middle-aged women. Magnetic resonance images of the knee were evaluated for the location and severity of cartilage defects, bone marrow lesions, osteophytes, subchondral cysts, meniscal and/or ligamentous tears, effusion, and synovitis among 363 middle-aged women (724 knees) from the Michigan Study of Women's Health Across the Nation. These findings were related to Kellgren-Lawrence osteoarthritis severity scores from radiographs, self-reported knee pain, self-reported knee injury, perception of physical functioning, and physical performance measures to assess mobility. Radiographs, physical performance assessment, and interviews were undertaken at the 1996 study baseline and again (with the addition of magnetic resonance imaging assessment) at the follow-up visit during 2007 to 2008. The prevalence of moderate-to-severe knee osteoarthritis changed from 3.7% at the baseline assessment to 26.7% at the follow-up visit eleven years later. Full-thickness cartilage defects of the medial, lateral, and patellofemoral compartments were present in 14.5% (105 knees), 4.6% (thirty-three knees), and 26.2% (190 knees), respectively. Synovitis was identified in 24.7% (179) of the knees, and joint effusions were observed in 70% (507 knees); 21.7% (157) of the knees had complex or macerated meniscal tears. Large osteophytes, marked synovitis, macerated meniscal tears, and full-thickness tibial cartilage defects were associated with increased odds of knee pain and with

  15. Kidney function changes with aging in adults: comparison between cross-sectional and longitudinal data analyses in renal function assessment.

    Science.gov (United States)

    Chung, Sang M; Lee, David J; Hand, Austin; Young, Philip; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas

    2015-12-01

    The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy. Copyright © 2015 John Wiley & Sons, Ltd.

  16. 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

  17. Influence of assessment setting on the results of functional analyses of problem behavior

    NARCIS (Netherlands)

    Lang, R.B.; Sigafoos, J.; Lancioni, G.E.; Didden, H.C.M.; Rispoli, M.

    2010-01-01

    Analogue functional analyses are widely used to identify the operant function of problem behavior in individuals with developmental disabilities. Because problem behavior often occurs across multiple settings (e.g., homes, schools, outpatient clinics), it is important to determine whether the

  18. Advances in supramolecular polymer chemistry : well-defined terpyridine-functionalized materials

    NARCIS (Netherlands)

    Ott, C.

    2008-01-01

    Controlled/"living" polymerization techniques have attracted enormous attention in the field of polymer science since they have opened an avenue to the preparation of well-defined materials with precisely designed molecular architectures like random, block, graft and comb copolymers. These

  19. Dairy shows different associations with abdominal and BMI-defined overweight: Cross-sectional analyses exploring a variety of dairy products.

    Science.gov (United States)

    Brouwer-Brolsma, E M; Sluik, D; Singh-Povel, C M; Feskens, E J M

    2018-05-01

    Previous studies have suggested weight-regulatory properties for several dairy nutrients, but population-based studies on dairy and body weight are inconclusive. We explored cross-sectional associations between dairy consumption and indicators of overweight. We included 114,682 Dutch adults, aged ≥18 years. Dairy consumption was quantified by a food frequency questionnaire. Abdominal overweight was defined as waist circumference (WC) ≥88 cm (women) or ≥102 cm (men) (n = 37,391), overweight as BMI ≥25-30 kg/m 2 (n = 44,772) and obesity as BMI ≥30 kg/m 2 (n = 15,339). Associations were quantified by logistic (abdominal overweight, no/yes), multinomial logistic (BMI-defined overweight and obesity) and linear regression analyses (continuous measures of WC and BMI), and they were adjusted for relevant covariates. Total dairy showed a positive association with abdominal overweight (OR Q1 ref vs. Q5: 1.09; 95% CI: 1.04-1.14) and with BMI-defined overweight (OR Q5 1.13; 95% CI: 1.08-1.18) and obesity (OR Q5 1.09; 95% CI: 1.02-1.16). Skimmed, semi-skimmed and non-fermented dairy also showed positive associations with overweight categories. Full-fat dairy showed an inverse association with overweight and obesity (OR Q5 for obesity: 0.78; 95% CI: 0.73-0.83). Moreover, inverse associations were observed for yoghurt and custard and positive associations for milk, buttermilk, flavoured yoghurt drinks, cheese and cheese snacks. Fermented dairy, curd cheese and Dutch cheese did not show a consistent association with overweight categories. Total, skimmed, semi-skimmed and non-fermented dairy; milk; buttermilk; flavoured yoghurt drinks; total cheese and cheese snacks showed a positive association with overweight categories, whereas full-fat dairy, custard and yoghurt showed an inverse association with overweight categories. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human

  20. Defining the Physiological Factors that Contribute to Postflight Changes in Functional Performance

    Science.gov (United States)

    Bloomberg, J. J.; Arzeno, N.; Buxton, R.; Feiveson, A. H.; Kofman, I.; Lawrence, E.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts, S. H.; hide

    2009-01-01

    Astronauts experience alterations in multiple physiological systems due to exposure to the microgravity conditions of space flight. These physiological changes include sensorimotor disturbances, cardiovascular deconditioning and loss of muscle mass and strength. These changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on lunar and Martian surfaces. To date, changes in functional performance have not been systematically studied or correlated with physiological changes. To understand how changes in physiological function impact functional performance an interdisciplinary pre/postflight testing regimen (Functional Task Test, FTT) has been developed that systematically evaluates both astronaut postflight functional performance and related physiological changes. The overall objective of the FTT is to identify the key underlying physiological factors that contribute to performance of functional tests that are representative of critical mission tasks. This study will identify which physiological systems contribute the most to impaired performance on each functional test. This will allow us to identify the physiological systems that play the largest role in decrement in functional performance. Using this information we can then design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight. The functional test battery was designed to address high priority tasks identified by the Constellation program as critical for mission success. The set of functional tests making up the FTT include the: 1) Seat Egress and Walk Test, 2) Ladder Climb Test, 3) Recovery from Fall/Stand Test, 4) Rock Translation Test, 5) Jump Down Test, 6) Torque Generation Test, and 7) Construction Activity Board Test. Corresponding physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor

  1. Defining the role of sensation, strength, and prehension for upper limb function in cervical spinal cord injury.

    Science.gov (United States)

    Kalsi-Ryan, Sukhvinder; Beaton, Dorcas; Curt, Armin; Duff, Susan; Jiang, Depeng; Popovic, Milos R; Rudhe, Claudia; Fehlings, Michael G; Verrier, Mary C

    2014-01-01

    Upper limb function plays a significant role in enhancing independence for individuals with tetraplegia. However, there is limited knowledge about the specific input of sensorimotor deficits on upper limb function. Thus the theoretical framework designed to develop the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) was used as a hypothetical model to analyze the impact of impairment on function. To define the association of impairment (sensation, strength, and prehension measured by the GRASSP) to upper limb function as defined by functional measures (Capabilities of Upper Extremity Questionnaire, Spinal Cord Independence Measure). A hypothetical model representing relationships by applying structural equation modeling was used to estimate the effect of the impairment domains in GRASSP on upper limb function. Data collected on 72 chronic individuals with tetraplegia was used to test the hypothetical model. Structural equation modeling confirmed strong associations between sensation, strength, and prehension with upper limb function, and determined 72% of the variance in "sensorimotor upper limb function" was explained by the model. Statistics of fit showed the data did fit the hypothesized model. Sensation and strength influence upper limb function directly and indirectly with prehension as the mediator. The GRASSP is a sensitive diagnostic tool in distinguishing the relative contribution of strength, sensation and prehension to function. Thus, the impact of interventions on specific domains of impairment and related contribution on clinical recovery of the upper limb can be detailed to optimize rehabilitation programs.

  2. Information processing architecture of functionally defined clusters in the macaque cortex.

    Science.gov (United States)

    Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R

    2012-11-28

    Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.

  3. Are Some Attitudes More Self-Defining Than Others? Assessing Self-Related Attitude Functions and Their Consequences.

    Science.gov (United States)

    Zunick, Peter V; Teeny, Jacob D; Fazio, Russell H

    2017-08-01

    Attitudes serve multiple functions, some related to the self-concept. We call attitudes that help people define who they are "self-defining." Across four studies, we tested a brief self-report measure of the extent to which an attitude is self-defining. Studies 1 and 2 showed that self-defining attitudes tend to be extreme, positive, and unambivalent. Studies 3 and 4 produced two main findings. First, self-definition was related to, but not redundant with, a number of other characteristics of the attitude (e.g., attitude certainty). Second, self-definition predicted participants' intentions to spontaneously advocate and, in Study 4, their reactions to an opportunity to advocate behaviorally (i.e., writing about their attitude in an optional response box) following a self-threat. Overall, the results highlight the utility of this approach and, more broadly, demonstrate the value of considering the role of the self in attitudinal processes, and vice versa.

  4. Further Refinements of Jensen’s Type Inequalities for the Function Defined on the Rectangle

    Directory of Open Access Journals (Sweden)

    M. Adil Khan

    2013-01-01

    Full Text Available We give refinement of Jensen’s type inequalities given by Bakula and Pečarić (2006 for the co-ordinate convex function. Also we establish improvement of Jensen’s inequality for the convex function of two variables.

  5. Ecological function as a target for ecosystem-based management: Defining when change matters in decision making

    Science.gov (United States)

    Ecosystem-based management (EBM) accounts for both direct and indirect drivers of ecological change for decision making. Just as with direct management of a resource, EBM requires a definition of management thresholds that define when change in function is sufficient to merit ma...

  6. The Functional Quality of Soluble Recombinant Polypeptides Produced in Escherichia coli Is Defined by a Wide Conformational Spectrum▿

    Science.gov (United States)

    Martínez-Alonso, Mónica; González-Montalbán, Nuria; García-Fruitós, Elena; Villaverde, Antonio

    2008-01-01

    We have observed that a soluble recombinant green fluorescent protein produced in Escherichia coli occurs in a wide conformational spectrum. This results in differently fluorescent protein fractions in which morphologically diverse soluble aggregates abound. Therefore, the functional quality of soluble versions of aggregation-prone recombinant proteins is defined statistically rather than by the prevalence of a canonical native structure. PMID:18836021

  7. On paranormed Zweier ideal convergent sequence spaces defined By Orlicz function

    Directory of Open Access Journals (Sweden)

    Bipan Hazarika

    2014-10-01

    Full Text Available In this article we introduce paranorm ideal convergent sequence spaces using Zweier transform and Orlicz function. We study some topological and algebraic properties. Further we prove some inclusion relations related to these new spaces.

  8. Synthetic alleles at position 121 define a functional domain of human interleukin-1 beta.

    Science.gov (United States)

    Ambrosetti, D C; Palla, E; Mirtella, A; Galeotti, C; Solito, E; Navarra, P; Parente, L; Melli, M

    1996-06-01

    The non-conservative substitution of the tyrosine residue at position 121 of human interleukin-1 beta (IL-1 beta) generates protein mutants showing strong reduction of the capacity to induce (a) prostaglandin E2 (PGE2) release from fibroblasts and smooth muscle cells, (b) murine T-cells proliferation and (c) activation of interleukin-6 (IL-6) gene expression. It is generally accepted that these functions are mediated by the type-I interleukin-1 receptor (IL-1RI). However, the mutant proteins maintain the binding affinity to the types-I and II IL-1 receptors, which is the same as the control IL-1 beta, suggesting that this amino acid substitution does not alter the structure of the molecule, except locally. Thus we have identified a new functional site of IL-1 beta different from the known receptor binding region, responsible for fundamental IL-1 beta functions. Moreover, we show that the same mutants maintain at least two hypothalamic functions, that is, the in vitro short-term PGE2 release from rat hypothalamus and the induction of fever in rabbits. This result suggests that there is yet another site of the molecule responsible for the hypothalamic functions, implying that multiple active sites on the IL-1 beta molecule, possibly binding to more than one receptor chain, trigger different signals.

  9. Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes.

    Directory of Open Access Journals (Sweden)

    Jyotica Batra

    Full Text Available Matrix metalloproteinases (MMPs play central roles in vertebrate tissue development, remodeling, and repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs, and the structural features that differentiate stronger from weaker complexes are poorly understood. Here we report the crystal structure of the comparatively weakly bound human MMP-10/TIMP-2 complex at 2.1 Å resolution. Comparison with previously reported structures of MMP-3/TIMP-1, MT1-MMP/TIMP-2, MMP-13/TIMP-2, and MMP-10/TIMP-1 complexes offers insights into the structural basis of binding selectivity. Our analyses identify a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces. The AB loop of the TIMP N-terminal domain and the contact loops of the TIMP C-terminal domain form highly variable peripheral contacts that can be considered as separate exosite interactions. In some complexes these exosite contacts are extensive, while in other complexes the AB loop or C-terminal domain contacts are greatly reduced and appear to contribute little to complex stability. Our data suggest that exosite interactions can enhance MMP/TIMP binding, although in the relatively weakly bound MMP-10/TIMP-2 complex they are not well optimized to do so. Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology.

  10. Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes.

    Science.gov (United States)

    Batra, Jyotica; Soares, Alexei S; Mehner, Christine; Radisky, Evette S

    2013-01-01

    Matrix metalloproteinases (MMPs) play central roles in vertebrate tissue development, remodeling, and repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs, and the structural features that differentiate stronger from weaker complexes are poorly understood. Here we report the crystal structure of the comparatively weakly bound human MMP-10/TIMP-2 complex at 2.1 Å resolution. Comparison with previously reported structures of MMP-3/TIMP-1, MT1-MMP/TIMP-2, MMP-13/TIMP-2, and MMP-10/TIMP-1 complexes offers insights into the structural basis of binding selectivity. Our analyses identify a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces. The AB loop of the TIMP N-terminal domain and the contact loops of the TIMP C-terminal domain form highly variable peripheral contacts that can be considered as separate exosite interactions. In some complexes these exosite contacts are extensive, while in other complexes the AB loop or C-terminal domain contacts are greatly reduced and appear to contribute little to complex stability. Our data suggest that exosite interactions can enhance MMP/TIMP binding, although in the relatively weakly bound MMP-10/TIMP-2 complex they are not well optimized to do so. Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology.

  11. Defining a similarity threshold for a functional proteinsequence pattern: The signal peptide cleavage site

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; von Heijne, Gunnar

    1996-01-01

    When preparing data sets of amino acid or nucleotide sequences it is necessary to exclude redundant or homologous sequences in order to avoid overestimating the predictive performance of an algorithm. For some time methods for doing this have been available in the area of protein structure...... prediction. We have developed a similar procedure based on pair-wise alignments for sequences with functional sites. We show how a correlation coefficient between sequence similarity and functional homology can be used to compare the efficiency of different similarity measures and choose a nonarbitrary...

  12. Experimental Approaches for Defining Functional Roles of Microbes in the Human Gut

    DEFF Research Database (Denmark)

    Dantas, Gautam; Sommer, Morten; Degnan, Patrick H.

    2013-01-01

    The complex and intimate relationship between humans and their gut microbial communities is becoming less obscure, due in part to large-scale gut microbial genome-sequencing projects and culture-independent surveys of the composition and gene content of these communities.These studies build upon...... ofmicrobial genome and community profiling projects, and the loss-of-function and gain-of-function strategies long employed in model organisms are now being extended to microbial genes, species, and communities from the human gut. These developments promise to deepen our understanding of human gut host...

  13. On the generating function of Poincare plots defining one dimensional perturbed Hamiltonian systems

    International Nuclear Information System (INIS)

    Montvai, A.

    1989-01-01

    A simple numerical method has been devised, for deriving the generating function of an arbitrary, one dimensional Hamiltonian system represented by its Poincare plot. In this case, the plot to be numerically processed is an area preserving transformation of a two-dimensional surface onto itself. Although the method in its present form is capable of treating only this case, there are no principal restrictions excluding the analysis of systems with higher dimensionality as well. As an example, the generating function of the motion of alpha particles in a nonsymmetric, toroidal magnetic field is derived and studied numerically. (orig.)

  14. Plant functional types define magnitude of drought response in peatland CO2 exchange

    NARCIS (Netherlands)

    Kuiper, J.J.; Mooij, W.M.; Bragazza, L.; Robroek, B.J.M.

    2014-01-01

    Peatlands are important sinks for atmospheric carbon (C), yet the role of plant functional types (PFTs) for C sequestration under climatic perturbations is still unclear. A plant removal experiment was used to study the importance of vascular PFTs for the net ecosystem CO2 exchange (NEE) during

  15. Plant functional types define magnitude of drought response in peatland CO2 exchange

    NARCIS (Netherlands)

    Kuiper, J.J.; Mooij, W.M.; Bragazza, L.; Robroek, B.J.M.

    2014-01-01

    Peatlands are important sinks for atmospheric carbon (C), yet the role of plant functional types (PFTs) for C sequestration under climatic perturbations is still unclear. A plant-removal experiment was used to study the importance of vascular PFTs for the net ecosystem CO2 exchange (NEE) during

  16. Defining the breeding goal for a sheep breed including production and functional traits using market data.

    Science.gov (United States)

    Theodoridis, A; Ragkos, A; Rose, G; Roustemis, D; Arsenos, G

    2017-11-16

    In this study, the economic values for production and functional traits of dairy sheep are estimated through the application of a profit function model using farm-level technical and economic data. The traits incorporated in the model were milk production, prolificacy, fertility, milking speed, longevity and mastitis occurrence. The economic values for these traits were derived as the approximate partial derivative of the specified profit function. A sensitivity analysis was also conducted in order to examine how potential changes in input and output prices would affect the breeding goal. The estimated economic values of the traits revealed their economic impact on the definition of the breeding goal for the specified production system. Milk production and fertility had the highest economic values (€40.30 and €20.28 per standard genetic deviation (SDa)), while, mastitis only had a low negative value of -0.57 €/SDa. Therefore, breeding for clinical mastitis will have a minor impact on farm profitability because it affects a small proportion of the flock and has low additive variance. The production traits, which include milk production, prolificacy and milking speed, contributed most to the breeding goal (70.0%), but functional traits still had a considerable share (30.0%). The results of this study highlight the importance of the knowledge of economic values of traits in the design of a breeding program. It is also suggested that the production and functional traits under consideration can be categorized as those which can be efficiently treated through genetic improvement (e.g. milk production and fertility) while others would be better dealt with through managerial interventions (e.g. mastitis occurrence). Also, sub-clinical mastitis that affects a higher proportion of flocks could have a higher contribution to breeding goals.

  17. Analysing Symbolic Expressions in Secondary School Chemistry: Their Functions and Implications for Pedagogy

    Science.gov (United States)

    Liu, Yu; Taber, Keith S.

    2016-01-01

    Symbolic expressions are essential resources for producing knowledge, yet they are a source of learning difficulties in chemistry education. This study aims to employ social semiotics to analyse the symbolic representation of chemistry from two complementary perspectives, referred to here as contextual (i.e., historical) and functional. First, the…

  18. Using riboswitches to regulate gene expression and define gene function in mycobacteria.

    Science.gov (United States)

    Van Vlack, Erik R; Seeliger, Jessica C

    2015-01-01

    Mycobacteria include both environmental species and many pathogenic species such as Mycobacterium tuberculosis, an intracellular pathogen that is the causative agent of tuberculosis in humans. Inducible gene expression is a powerful tool for examining gene function and essentiality, both in in vitro culture and in host cell infections. The theophylline-inducible artificial riboswitch has recently emerged as an alternative to protein repressor-based systems. The riboswitch is translationally regulated and is combined with a mycobacterial promoter that provides transcriptional control. We here provide methods used by our laboratory to characterize the riboswitch response to theophylline in reporter strains, recombinant organisms containing riboswitch-regulated endogenous genes, and in host cell infections. These protocols should facilitate the application of both existing and novel artificial riboswitches to the exploration of gene function in mycobacteria. © 2015 Elsevier Inc. All rights reserved.

  19. Defining planktonic protist functional groups on mechanisms for energy and nutrient acquisition

    DEFF Research Database (Denmark)

    Mitra, Aditee; Flynn, Kevin J.; Tillmann, Urban

    2016-01-01

    Arranging organisms into functional groups aids ecological research by grouping organisms (irrespective of phylogenetic origin) that interact with environmental factors in similar ways. Planktonic protists traditionally have been split between photoautotrophic “phytoplankton” and phagotrophic...... “microzooplankton”. However, there is a growing recognition of the importance of mixotrophy in euphotic aquatic systems, where many protists often combine photoautotrophic and phagotrophic modes of nutrition. Such organisms do not align with the traditional dichotomy of phytoplankton and microzooplankton...... for phototrophy, and (iv) non-constitutive mixotrophs (NCMs) that acquire their phototrophic capacity by ingesting specific (SNCM) or general non-specific (GNCM) prey. For the first time, we incorporate these functional groups within a foodweb structure and show, using model outputs, that there is scope...

  20. Using Bilateral Functional and Anthropometric Tests to Define Symmetry in Cross-Country Skiers

    Directory of Open Access Journals (Sweden)

    Björklund Glenn

    2017-12-01

    Full Text Available The aim of this study was to evaluate the symmetry of anthropometry and muscle function in cross-country skiers and their association to vertical jumping power. Twenty cross-country skiers were recruited (21.7 ± 3.8 yrs, 180.6 ± 7.6 cm, 73.2 ± 7.6 kg. Anthropometric data was obtained using an iDXA scan. VO2max was determined using the diagonal stride technique on a ski treadmill. Bilateral functional tests for the upper and lower body were the handgrip and standing heel-rise tests. Vertical jump height and power were assessed with a counter movement jump. Percent asymmetry was calculated using a symmetry index and four absolute symmetry index levels. At a group level the upper body was more asymmetrical with regard to lean muscle mass (p = 0.022, d = 0.17 and functional strength (p = 0.019, d = 0.51 than the lower body. At an individual level the expected frequencies for absolute symmetry level indexes showed the largest deviation from zero for the heel-rise test (χ2 = 16.97, p = 0.001, while the leg lean mass deviated the least (χ2 = 0.42, p = 0.517. No relationships were observed between absolute symmetry level indexes of the lower body and counter movement jump performance (p > 0.05. As a group the skiers display a more asymmetrical upper body than lower body regarding muscle mass and strength. Interestingly at the individual level, despite symmetrical lean leg muscle mass the heel-rise test showed the largest asymmetry. This finding indicates a mismatch in muscle function for the lower body.

  1. Using Bilateral Functional and Anthropometric Tests to Define Symmetry in Cross-Country Skiers.

    Science.gov (United States)

    Björklund, Glenn; Alricsson, Marie; Svantesson, Ulla

    2017-12-01

    The aim of this study was to evaluate the symmetry of anthropometry and muscle function in cross-country skiers and their association to vertical jumping power. Twenty cross-country skiers were recruited (21.7 ± 3.8 yrs, 180.6 ± 7.6 cm, 73.2 ± 7.6 kg). Anthropometric data was obtained using an iDXA scan. VO 2max was determined using the diagonal stride technique on a ski treadmill. Bilateral functional tests for the upper and lower body were the handgrip and standing heel-rise tests. Vertical jump height and power were assessed with a counter movement jump. Percent asymmetry was calculated using a symmetry index and four absolute symmetry index levels. At a group level the upper body was more asymmetrical with regard to lean muscle mass (p = 0.022, d = 0.17) and functional strength (p = 0.019, d = 0.51) than the lower body. At an individual level the expected frequencies for absolute symmetry level indexes showed the largest deviation from zero for the heel-rise test (χ2 = 16.97, p = 0.001), while the leg lean mass deviated the least (χ2 = 0.42, p = 0.517). No relationships were observed between absolute symmetry level indexes of the lower body and counter movement jump performance (p > 0.05). As a group the skiers display a more asymmetrical upper body than lower body regarding muscle mass and strength. Interestingly at the individual level, despite symmetrical lean leg muscle mass the heel-rise test showed the largest asymmetry. This finding indicates a mismatch in muscle function for the lower body.

  2. Defining ATM-Independent Functions of the Mre11 Complex with a Novel Mouse Model.

    Science.gov (United States)

    Balestrini, Alessia; Nicolas, Laura; Yang-Lott, Katherine; Guryanova, Olga A; Levine, Ross L; Bassing, Craig H; Chaudhuri, Jayanta; Petrini, John H J

    2016-02-01

    The Mre11 complex (Mre11, Rad50, and Nbs1) occupies a central node of the DNA damage response (DDR) network and is required for ATM activation in response to DNA damage. Hypomorphic alleles of MRE11 and NBS1 confer embryonic lethality in ATM-deficient mice, indicating that the complex exerts ATM-independent functions that are essential when ATM is absent. To delineate those functions, a conditional ATM allele (ATM(flox)) was crossed to hypomorphic NBS1 mutants (Nbs1(ΔB/ΔB) mice). Nbs1(ΔB/ΔB) Atm(-/-) hematopoietic cells derived by crossing to vav(cre) were viable in vivo. Nbs1(ΔB/ΔB) Atm(-/-) (VAV) mice exhibited a pronounced defect in double-strand break repair and completely penetrant early onset lymphomagenesis. In addition to repair defects observed, fragile site instability was noted, indicating that the Mre11 complex promotes genome stability upon replication stress in vivo. The data suggest combined influences of the Mre11 complex on DNA repair, as well as the responses to DNA damage and DNA replication stress. A novel mouse model was developed, by combining a vav(cre)-inducible ATM knockout mouse with an NBS1 hypomorphic mutation, to analyze ATM-independent functions of the Mre11 complex in vivo. These data show that the DNA repair, rather than DDR signaling functions of the complex, is acutely required in the context of ATM deficiency to suppress genome instability and lymphomagenesis. ©2015 American Association for Cancer Research.

  3. Defining structural and functional dimensions of the extracellular thyrotropin receptor region.

    Science.gov (United States)

    Kleinau, Gunnar; Mueller, Sandra; Jaeschke, Holger; Grzesik, Paul; Neumann, Susanne; Diehl, Anne; Paschke, Ralf; Krause, Gerd

    2011-06-24

    The extracellular region of the thyrotropin receptor (TSHR) can be subdivided into the leucine-rich repeat domain (LRRD) and the hinge region. Both the LRRD and the hinge region interact with thyrotropin (TSH) or autoantibodies. Structural data for the TSHR LRRD were previously determined by crystallization (amino acids Glu(30)-Thr(257), 10 repeats), but the structure of the hinge region is still undefined. Of note, the amino acid sequence (Trp(258)-Tyr(279)) following the crystallized LRRD comprises a pattern typical for leucine-rich repeats with conserved hydrophobic side chains stabilizing the repeat fold. Moreover, functional data for amino acids between the LRRD and the transmembrane domain were fragmentary. We therefore investigated systematically these TSHR regions by mutagenesis to reveal insights into their functional contribution and potential structural features. We found that mutations of conserved hydrophobic residues between Thr(257) and Tyr(279) cause TSHR misfold, which supports a structural fold of this peptide, probably as an additional leucine-rich repeat. Furthermore, we identified several new mutations of hydrophilic amino acids in the entire hinge region leading to partial TSHR inactivation, indicating that these positions are important for intramolecular signal transduction. In summary, we provide new information regarding the structural features and functionalities of extracellular TSHR regions. Based on these insights and in context with previous results, we suggest an extracellular activation mechanism that supports an intramolecular agonistic unit as a central switch for activating effects at the extracellular region toward the serpentine domain.

  4. The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes

    Science.gov (United States)

    van Overbeek, Leonard S.; Berg, Gabriele; Pirttilä, Anna Maria; Compant, Stéphane; Campisano, Andrea; Döring, Matthias; Sessitsch, Angela

    2015-01-01

    SUMMARY All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions. PMID:26136581

  5. Minimization of Linear Functionals Defined on| Solutions of Large-Scale Discrete Ill-Posed Problems

    DEFF Research Database (Denmark)

    Elden, Lars; Hansen, Per Christian; Rojas, Marielba

    2003-01-01

    The minimization of linear functionals de ned on the solutions of discrete ill-posed problems arises, e.g., in the computation of con dence intervals for these solutions. In 1990, Elden proposed an algorithm for this minimization problem based on a parametric-programming reformulation involving...... the solution of a sequence of trust-region problems, and using matrix factorizations. In this paper, we describe MLFIP, a large-scale version of this algorithm where a limited-memory trust-region solver is used on the subproblems. We illustrate the use of our algorithm in connection with an inverse heat...

  6. Fixed points for some non-obviously contractive operators defined in a space of continuous functions

    OpenAIRE

    C. Avramescu; Cristian Vladimirescu

    2004-01-01

    Let $X$ be an arbitrary (real or complex) Banach space, endowed with the norm $\\left| \\cdot \\right| .$ Consider the space of the continuous functions $C\\left( \\left[ 0,T\\right] ,X\\right) $ $\\left( T>0\\right) $, endowed with the usual topology, and let $M$ be a closed subset of it. One proves that each operator $A:M\\rightarrow M$ fulfilling for all $x,y\\in M$ and for all $t\\in \\left[ 0,T\\right] $ the condition \\begin{eqnarray*} \\left| \\left( Ax\\right) \\left( t\\right) -\\left( Ay\\right) \\l...

  7. Functional approach for pairing in finite systems: How to define restoration of broken symmetries in Energy Density Functional theory?

    International Nuclear Information System (INIS)

    Hupin, G; Lacroix, D; Bender, M

    2011-01-01

    The Multi-Reference Energy Density Functional (MR-EDF) approach (also called configuration mixing or Generator Coordinate Method), that is commonly used to treat pairing in finite nuclei and project onto particle number, is re-analyzed. It is shown that, under certain conditions, the MR-EDF energy can be interpreted as a functional of the one-body density matrix of the projected state with good particle number. Based on this observation, we propose a new approach, called Symmetry-Conserving EDF (SC-EDF), where the breaking and restoration of symmetry are accounted for simultaneously. We show, that such an approach is free from pathologies recently observed in MR-EDF and can be used with a large flexibility on the density dependence of the functional.

  8. The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes.

    Science.gov (United States)

    Hardoim, Pablo R; van Overbeek, Leonard S; Berg, Gabriele; Pirttilä, Anna Maria; Compant, Stéphane; Campisano, Andrea; Döring, Matthias; Sessitsch, Angela

    2015-09-01

    All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous hMSC...... population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high...... and adipocytes on the basis of gene expression and protein production of lineage-specific markers. In vivo, hMSC-CD146(+) and hMSC-CD146(-) cells formed bone and bone marrow organ when implanted subcutaneously in immune-deficient mice. Bone was enriched in hMSC-CD146(-) cells (12.6 % versus 8.1 %) and bone...

  10. Introducing Alternative-Based Thresholding for Defining Functional Regions of Interest in fMRI

    Directory of Open Access Journals (Sweden)

    Jasper Degryse

    2017-04-01

    Full Text Available In fMRI research, one often aims to examine activation in specific functional regions of interest (fROIs. Current statistical methods tend to localize fROIs inconsistently, focusing on avoiding detection of false activation. Not missing true activation is however equally important in this context. In this study, we explored the potential of an alternative-based thresholding (ABT procedure, where evidence against the null hypothesis of no effect and evidence against a prespecified alternative hypothesis is measured to control both false positives and false negatives directly. The procedure was validated in the context of localizer tasks on simulated brain images and using a real data set of 100 runs per subject. Voxels categorized as active with ABT can be confidently included in the definition of the fROI, while inactive voxels can be confidently excluded. Additionally, the ABT method complements classic null hypothesis significance testing with valuable information by making a distinction between voxels that show evidence against both the null and alternative and voxels for which the alternative hypothesis cannot be rejected despite lack of evidence against the null.

  11. Plant functional types define magnitude of drought response in peatland CO2 exchange.

    Science.gov (United States)

    Kuiper, Jan J; Mooij, Wolf M; Bragazza, Luca; Robroek, Bjorn J M

    2014-01-01

    Peatlands are important sinks for atmospheric carbon (C), yet the role of plant functional types (PFTs) for C sequestration under climatic perturbations is still unclear. A plant-removal experiment was used to study the importance of vascular PFTs for the net ecosystem CO2 exchange (NEE) during (i.e., resistance) and after (i.e., recovery) an experimental drought. The removal of PFTs caused a decrease of NEE, but the rate differed between microhabitats (i.e., hummocks and lawns) and the type of PFTs. Ericoid removal had a large effect on NEE in hummocks, while the graminoids played a major role in the lawns. The removal of PFTs did not affect the resistance or the recovery after the experimental drought. We argue that the response of Sphagnum mosses (the only PFT present in all treatments) to drought is dominant over that of coexisting PFTs. However, we observed that the moment in time when the system switched from C sink to C source during the drought was controlled by the vascular PFTs. In the light of climate change, the shifts in species composition or even the loss of certain PFTs are expected to strongly affect the future C dynamics in response to environmental stress.

  12. Practical background modification fermented beverage technology for the formation of defined functional properties

    Directory of Open Access Journals (Sweden)

    V. V. Botvinnikova

    2016-01-01

    Full Text Available The problem of provision of population with dairy products is escalating due to the fact that today, throughout the world, particularly in Russia, there is a shortage of milk as raw material, increasing every year. In the future, the consumption of milk and dairy products will continue to outpace growth in milk production is solid. To solve this problem, domestic producers need to find new ways to increase production of raw milk and improve the consumer and functional properties of fermented dairy products. The work was proposed the use of acoustic effects of ultrasound, triggered by the ultrasound, the technological model UTA ABOUT, 4/22 OM (frequency mechanical vibrations 22 ± 1,65 kHz. The main factors determining consumer characteristics, were taken physico-chemical parameters, structural and mechanical characteristics and the accumulation of minor biologically active substances – kefiran. In the study was obtained results confirming the necessity of using ultrasonic impact (RAS in the production technology of dairy products.

  13. Viewing the human microbiome through three-dimensional glasses: integrating structural and functional studies to better define the properties of myriad carbohydrate-active enzymes

    International Nuclear Information System (INIS)

    Turnbaugh, Peter J.; Henrissat, Bernard; Gordon, Jeffrey I.

    2010-01-01

    Metagenomics has unleashed a deluge of sequencing data describing the organismal, genetic, and transcriptional diversity of the human microbiome. To better understand the precise functions of the myriad proteins encoded by the microbiome, including carbohydrate-active enzymes, it will be critical to combine structural studies with functional analyses. Recent studies have provided an unprecedented view of the trillions of microbes associated with the human body. The human microbiome harbors tremendous diversity at multiple levels: the species that colonize each individual and each body habitat; the genes that are found in each organism’s genome; the expression of these genes and the interactions and activities of their protein products. The sources of this diversity are wide-ranging and reflect both environmental and host factors. A major challenge moving forward is defining the precise functions of members of various families of proteins represented in our microbiomes, including the highly diverse carbohydrate-active enzymes (CAZymes) involved in numerous biologically important chemical transformations, such as the degradation of complex dietary polysaccharides. Coupling metagenomic analyses to structural genomics initiatives and to biochemical and other functional assays of CAZymes will be essential for determining how these as well as other microbiome-encoded proteins operate to shape the properties of microbial communities and their human hosts

  14. Defining functioning levels in patients with schizophrenia: A combination of a novel clustering method and brain SPECT analysis.

    Science.gov (United States)

    Catherine, Faget-Agius; Aurélie, Vincenti; Eric, Guedj; Pierre, Michel; Raphaëlle, Richieri; Marine, Alessandrini; Pascal, Auquier; Christophe, Lançon; Laurent, Boyer

    2017-12-30

    This study aims to define functioning levels of patients with schizophrenia by using a method of interpretable clustering based on a specific functioning scale, the Functional Remission Of General Schizophrenia (FROGS) scale, and to test their validity regarding clinical and neuroimaging characterization. In this observational study, patients with schizophrenia have been classified using a hierarchical top-down method called clustering using unsupervised binary trees (CUBT). Socio-demographic, clinical, and neuroimaging SPECT perfusion data were compared between the different clusters to ensure their clinical relevance. A total of 242 patients were analyzed. A four-group functioning level structure has been identified: 54 are classified as "minimal", 81 as "low", 64 as "moderate", and 43 as "high". The clustering shows satisfactory statistical properties, including reproducibility and discriminancy. The 4 clusters consistently differentiate patients. "High" functioning level patients reported significantly the lowest scores on the PANSS and the CDSS, and the highest scores on the GAF, the MARS and S-QoL 18. Functioning levels were significantly associated with cerebral perfusion of two relevant areas: the left inferior parietal cortex and the anterior cingulate. Our study provides relevant functioning levels in schizophrenia, and may enhance the use of functioning scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 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

  16. Using analyses of amino Acid coevolution to understand protein structure and function.

    Science.gov (United States)

    Ashenberg, Orr; Laub, Michael T

    2013-01-01

    Determining which residues of a protein contribute to a specific function is a difficult problem. Analyses of amino acid covariation within a protein family can serve as a useful guide by identifying residues that are functionally coupled. Covariation analyses have been successfully used on several different protein families to identify residues that work together to promote folding, enable protein-protein interactions, or contribute to an enzymatic activity. Covariation is a statistical signal that can be measured in a multiple sequence alignment of homologous proteins. As sequence databases have expanded dramatically, covariation analyses have become easier and more powerful. In this chapter, we describe how functional covariation arises during the evolution of proteins and how this signal can be distinguished from various background signals. We discuss the basic methodology for performing amino acid covariation analysis, using bacterial two-component signal transduction proteins as an example. We provide practical suggestions for each step of the process including assembly of protein sequences, construction of a multiple sequence alignment, measurement of covariation, and analysis of results. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

    Science.gov (United States)

    Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A

    2016-01-15

    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections.

  18. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

    Science.gov (United States)

    Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A.

    2016-01-01

    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. PMID:26784220

  19. A Service-Oriented Approach for Dynamic Chaining of Virtual Network Functions over Multi-Provider Software-Defined Networks

    Directory of Open Access Journals (Sweden)

    Barbara Martini

    2016-06-01

    Full Text Available Emerging technologies such as Software-Defined Networks (SDN and Network Function Virtualization (NFV promise to address cost reduction and flexibility in network operation while enabling innovative network service delivery models. However, operational network service delivery solutions still need to be developed that actually exploit these technologies, especially at the multi-provider level. Indeed, the implementation of network functions as software running over a virtualized infrastructure and provisioned on a service basis let one envisage an ecosystem of network services that are dynamically and flexibly assembled by orchestrating Virtual Network Functions even across different provider domains, thereby coping with changeable user and service requirements and context conditions. In this paper we propose an approach that adopts Service-Oriented Architecture (SOA technology-agnostic architectural guidelines in the design of a solution for orchestrating and dynamically chaining Virtual Network Functions. We discuss how SOA, NFV, and SDN may complement each other in realizing dynamic network function chaining through service composition specification, service selection, service delivery, and placement tasks. Then, we describe the architecture of a SOA-inspired NFV orchestrator, which leverages SDN-based network control capabilities to address an effective delivery of elastic chains of Virtual Network Functions. Preliminary results of prototype implementation and testing activities are also presented. The benefits for Network Service Providers are also described that derive from the adaptive network service provisioning in a multi-provider environment through the orchestration of computing and networking services to provide end users with an enhanced service experience.

  20. Design and synthesis of structurally well-defined functional polypropylenes via transition metal-mediated olefin polymerization chemistry

    Institute of Scientific and Technical Information of China (English)

    Dong Jinyong

    2006-01-01

    Functionalization of polyolefins is an industrially important yet scientifically challenging research subject.This paper summarizes our recent effort to access structurally well-defined functional polypropylenes via transition metal-mediated olefin polymerization.In one approach,polypropylenes containing side chain functional groups of controlled concentrations were obtained by Ziegler-Natta-catalyzed copolymerization of propylene in combination with either living anionic or controlled radical polymerization of polar monomers.The copolymerization of propylene with 1,4-divinylbenzene using an isospecific MgC12-supported TIC14 catalyst yielded potypropylenes containing pendant styrene moieties.Both metalation reaction with n-butyllithium and hydrochlorination reaction with dry hydrogen chloride selectively and quantitatively occurred at the pendant reactive sites,generating polymeric benzyllithium and 1-chloroethylbenzene species.These species initiated living anionic polymerization of styrene(S)and atom transfer radical polymerization(in the presence of CuC1 and pentamethyldiethylenetriamine) of methyl methacrylate(MMA),respectively,resulting in functional polypropylene graft copolymers(PP-g-PS and PP-g-PMMA)with controllable graft lengths.In another approach,chain end-functionalized polypropylenes containing a terminal OH-group with controlled molecular weights were directly prepared by propylene polymerization with a metaUocene catalyst through a selective aluminum chain transfer reaction.Both approaches proved to be desirable polyolefin functionalization routes in terms of efficiency and polymer structure controllability.

  1. Lung function in idiopathic pulmonary fibrosis - extended analyses of the IFIGENIA trial

    Directory of Open Access Journals (Sweden)

    Verschakelen Johny

    2009-10-01

    Full Text Available Abstract Background The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down disease progression in terms of vital capacity (VC (+9% and diffusing capacity (DLco (+24% in idiopathic pulmonary fibrosis (IPF. To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. Methods We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI, and mortality in the 155 study-patients. Results In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. Conclusion This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study. Trial Registration Registered at http://www.ClinicalTrials.gov; number NCT00639496.

  2. Characterization and functional analyses of the human G protein-coupled receptor kinase 4 gene promoter.

    Science.gov (United States)

    Hasenkamp, Sandra; Telgmann, Ralph; Staessen, Jan A; Hagedorn, Claudia; Dördelmann, Corinna; Bek, Martin; Brand-Herrmann, Stefan-Martin; Brand, Eva

    2008-10-01

    The G protein-coupled receptor kinase 4 is involved in renal sodium handling and blood pressure regulation. Missense variants have already been tested functionally and are associated with hypertension, but no data on promoter analyses are yet available. We scanned 94 hypertensive white subjects for genetic variation and performed promoter reporter gene analyses in HEK293T, COS7, and SaOs-2 cells. Transient transfections with various full lengths and wild-type deletion constructs revealed that 1851 bp of the flanking region and 275 bp of the 5'-untranslated region were sufficient for transcriptional activities and composed a powerful cis-active element in the distal 293 bp. The -1702T and +2T alleles resulted in drastic general reductions of promoter function, whereas an activity increasing effect of +268C was cell type specific. Electrophoretic mobility-shift assay, supershift, and cotransfection analyses of transcription factor binding sites predicted in silico (Alibaba2.1/Transfac7) resulted in allele-specific binding patterns of nuclear proteins and identified the participation of CCAAT/enhancer-binding protein transcription factor family members. The G protein-coupled receptor kinase 4 core promoter resides in the first 1851 bp upstream of its transcription start site. The 4 identified genetic variants within this region exert allele-specific impact on both cell type- and stimulation-dependent transcription and may affect the expression balance of renal G protein-coupled receptor kinase 4.

  3. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    Directory of Open Access Journals (Sweden)

    Ari J S Ferreira

    Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  4. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S

    2014-06-12

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  5. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

    2014-01-01

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  6. The effects of ropivacaine hydrochloride on platelet function: an assessment using the platelet function analyser (PFA-100).

    LENUS (Irish Health Repository)

    Porter, J

    2012-02-03

    Amide local anaesthetics impair blood clotting in a concentration-dependent manner by inhibition of platelet function and enhanced fibrinolysis. We hypothesised that the presence of ropivacaine in the epidural space could decrease the efficacy of an epidural blood patch, as this technique requires that the injected blood can clot in order to be effective. Ropivacaine is an aminoamide local anaesthetic used increasingly for epidural analgesia during labour. The concentration of local anaesthetic in blood achieved in the epidural space during the performance of an epidural blood patch is likely to be the greatest which occurs (intentionally) in any clinical setting. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur: (i) clinically in the epidural space and (ii) in plasma during an epidural infusion of ropivacaine, alter platelet function. A platelet function analyser (Dade PFA-100, Miami) was employed to assess the effects of ropivacaine-treated blood on platelet function. The greater concentrations of ropivacaine studied (3.75 and 1.88 mg x ml(-1)), which correspond to those which could occur in the epidural space, produced significant inhibition of platelet aggregation. We conclude that the presence of ropivacaine in the epidural space may decrease the efficacy of an early or prophylactic epidural blood patch.

  7. Statistical and extra-statistical considerations in differential item functioning analyses

    Directory of Open Access Journals (Sweden)

    G. K. Huysamen

    2004-10-01

    Full Text Available This article briefly describes the main procedures for performing differential item functioning (DIF analyses and points out some of the statistical and extra-statistical implications of these methods. Research findings on the sources of DIF, including those associated with translated tests, are reviewed. As DIF analyses are oblivious of correlations between a test and relevant criteria, the elimination of differentially functioning items does not necessarily improve predictive validity or reduce any predictive bias. The implications of the results of past DIF research for test development in the multilingual and multi-cultural South African society are considered. Opsomming Hierdie artikel beskryf kortliks die hoofprosedures vir die ontleding van differensiële itemfunksionering (DIF en verwys na sommige van die statistiese en buite-statistiese implikasies van hierdie metodes. ’n Oorsig word verskaf van navorsingsbevindings oor die bronne van DIF, insluitend dié by vertaalde toetse. Omdat DIF-ontledings nie die korrelasies tussen ’n toets en relevante kriteria in ag neem nie, sal die verwydering van differensieel-funksionerende items nie noodwendig voorspellingsgeldigheid verbeter of voorspellingsydigheid verminder nie. Die implikasies van vorige DIF-navorsingsbevindings vir toetsontwikkeling in die veeltalige en multikulturele Suid-Afrikaanse gemeenskap word oorweeg.

  8. Structural and functional analyses of the putrescine binding protein PotF from Xanthomonas citri

    Energy Technology Data Exchange (ETDEWEB)

    Santana, L.D.F.; Balan, A. [Laboratorio Nacional de Biociencias - LNBIO, Campinas, SP (Brazil)

    2012-07-01

    Full text: The focus of our group is to determinate the role of ABC transporters in the physiology and growth of Xanthomonas citri, a phytopathogenic bacteria that infects citrus plants causing significant losses for the economy. One of the ABC transporters identified in the X. citri genome and that was showed to be active during the infection in Citrus sinensis plants was the putrescine transporter. This transporter consists of two internal membrane proteins PotG and PotH that form a pore, a cytoplasmic protein that gives energy for the transport and the periplasmic-binding protein PotF, which is responsible for the affinity and specificity of the system. Its function is associated to the microbial carcinogenesis, biofilm formation, escape from phagolysosomes, bacteriocin production, toxin activity and protection from oxidative and acid stress. In this work, we show for the first time, the expression, purification, functional and structural analyses of the X. citri PotF protein. The PotF was expressed from Escherichia coli cells strain Arctic, as a 40 kDa soluble protein, after induction of IPTG for twenty four hours at thirteen deg C. Using immobilized metal affinity chromatography for purification, the protein was eluted in the fractions with 10-500 mM of imidazole. To test the folding and cability to bind putrescine, spectroscopic analyses were performed using circular dichroism and intrinsic fluorescence. The data showed that PotF suffers conformational changes in presence of ligands and in different pH, suggesting a possible interaction with the tested ligand. Moreover, based on bioinformatics studies and molecular modeling analyses, we showed that X. citri PotF is highly conserved when compared to orthologs present in other bacteria, including the residues that form the ligand-binding site. The production of PotF in a soluble and stable form will allow us to start the crystallization trials in attempt to solve its structure. (author)

  9. Structural and functional analyses of the putrescine binding protein PotF from Xanthomonas citri

    International Nuclear Information System (INIS)

    Santana, L.D.F.; Balan, A.

    2012-01-01

    Full text: The focus of our group is to determinate the role of ABC transporters in the physiology and growth of Xanthomonas citri, a phytopathogenic bacteria that infects citrus plants causing significant losses for the economy. One of the ABC transporters identified in the X. citri genome and that was showed to be active during the infection in Citrus sinensis plants was the putrescine transporter. This transporter consists of two internal membrane proteins PotG and PotH that form a pore, a cytoplasmic protein that gives energy for the transport and the periplasmic-binding protein PotF, which is responsible for the affinity and specificity of the system. Its function is associated to the microbial carcinogenesis, biofilm formation, escape from phagolysosomes, bacteriocin production, toxin activity and protection from oxidative and acid stress. In this work, we show for the first time, the expression, purification, functional and structural analyses of the X. citri PotF protein. The PotF was expressed from Escherichia coli cells strain Arctic, as a 40 kDa soluble protein, after induction of IPTG for twenty four hours at thirteen deg C. Using immobilized metal affinity chromatography for purification, the protein was eluted in the fractions with 10-500 mM of imidazole. To test the folding and cability to bind putrescine, spectroscopic analyses were performed using circular dichroism and intrinsic fluorescence. The data showed that PotF suffers conformational changes in presence of ligands and in different pH, suggesting a possible interaction with the tested ligand. Moreover, based on bioinformatics studies and molecular modeling analyses, we showed that X. citri PotF is highly conserved when compared to orthologs present in other bacteria, including the residues that form the ligand-binding site. The production of PotF in a soluble and stable form will allow us to start the crystallization trials in attempt to solve its structure. (author)

  10. Cross-study analysis of genomic data defines the ciliate multigenic epiplasmin family: strategies for functional analysis in Paramecium tetraurelia

    Directory of Open Access Journals (Sweden)

    Ravet Viviane

    2009-06-01

    Full Text Available Abstract Background The sub-membranous skeleton of the ciliate Paramecium, the epiplasm, is composed of hundreds of epiplasmic scales centered on basal bodies, and presents a complex set of proteins, epiplasmins, which belong to a multigenic family. The repeated duplications observed in the P. tetraurelia genome present an interesting model of the organization and evolution of a multigenic family within a single cell. Results To study this multigenic family, we used phylogenetic, structural, and analytical transcriptional approaches. The phylogenetic method defines 5 groups of epiplasmins in the multigenic family. A refined analysis by Hydrophobic Cluster Analysis (HCA identifies structural characteristics of 51 epiplasmins, defining five separate groups, and three classes. Depending on the sequential arrangement of their structural domains, the epiplasmins are defined as symmetric, asymmetric or atypical. The EST data aid in this classification, in the identification of putative regulating sequences such as TATA or CAAT boxes. When specific RNAi experiments were conducted using sequences from either symmetric or asymmetric classes, phenotypes were drastic. Local effects show either disrupted or ill-shaped epiplasmic scales. In either case, this results in aborted cell division. Using structural features, we show that 4 epiplasmins are also present in another ciliate, Tetrahymena thermophila. Their affiliation with the distinctive structural groups of Paramecium epiplasmins demonstrates an interspecific multigenic family. Conclusion The epiplasmin multigenic family illustrates the history of genomic duplication in Paramecium. This study provides a framework which can guide functional analysis of epiplasmins, the major components of the membrane skeleton in ciliates. We show that this set of proteins handles an important developmental information in Paramecium since maintenance of epiplasm organization is crucial for cell morphogenesis.

  11. Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.

    Science.gov (United States)

    Berry, Rachel; Miyagawa, Taimei; Paskaranandavadivel, Niranchan; Du, Peng; Angeli, Timothy R; Trew, Mark L; Windsor, John A; Imai, Yohsuke; O'Grady, Gregory; Cheng, Leo K

    2016-11-01

    High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm 2 ) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration. Copyright © 2016 the American Physiological Society.

  12. Recombinant vitronectin is a functionally defined substrate that supports human embryonic stem cell self-renewal via alphavbeta5 integrin.

    NARCIS (Netherlands)

    Braam, S.R.; Zeinstra, L.M.; Litjens, S.H.M.; Ward-van Oostwaard, D.; van den Brink, S.; van Laake, L.W.; Lebrin, F.; Kats, P.; Hochstenbach, R.; Passier, R.; Sonnenberg, A.; Mummery, C.L.

    2008-01-01

    Defined growth conditions are essential for many applications of human embryonic stem cells (hESC). Most defined media are presently used in combination with Matrigel, a partially defined extracellular matrix (ECM) extract from mouse sarcoma. Here, we defined ECM requirements of hESC by analyzing

  13. 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

  14. Analysing the relationship between traumatic biographical events and the current structural functioning of personality.

    Science.gov (United States)

    Schiltz, L; Schiltz, J

    2008-01-01

    We present the general structure of a multi-annual research project. Our general expectancy concerns the possibilities of arts psychotherapy as a means of launching the blocked process of subjectivation with people suffering from exclusion, precarity and marginalization. The research project follows a complex research design with a sequential strategy, the first part consisting in an integrated psychosocial and clinical study using a mixed methodology. We constructed special rating scales for the analysis of the data of a semi-structured biographical interview and also for the holistic interpretation of the Rotter Blank Sentences Test, separating the associations to sentences beginning with the third and first person. The correlations between two sets of variables (biographical interview and Rotter test) were computed for the total experimental group (N=206), and for clinical subgroups. We shall analyse the matrices of correlations (Spearman's Rho) with the help of optimal scaling procedures (OVERALS). The links between traumatic biographical events and responses to the 3rd, respectively 1st person items of the Rotter test are interpreted in terms of unconscious versus conscious psychological processes and allow us analysing the expression of defence mechanisms and coping strategies. The results of the study are discussed in the light of the recent traumatogenic hypothesis of borderline functioning.

  15. Relationships of Functional Tests Following ACL Reconstruction: Exploratory Factor Analyses of the Lower Extremity Assessment Protocol.

    Science.gov (United States)

    DiFabio, Melissa; Slater, Lindsay V; Norte, Grant; Goetschius, John; Hart, Joseph M; Hertel, Jay

    2018-03-01

    After ACL reconstruction (ACLR), deficits are often assessed using a variety of functional tests, which can be time consuming. It is unknown whether these tests provide redundant or unique information. To explore relationships between components of a battery of functional tests, the Lower Extremity Assessment Protocol (LEAP) was created to aid in developing the most informative, concise battery of tests for evaluating ACLR patients. Descriptive, cross-sectional. Laboratory. 76 ACLR patients (6.86±3.07 months postoperative) and 54 healthy participants. Isokinetic knee flexion and extension at 90 and 180 degrees/second, maximal voluntary isometric contraction for knee extension and flexion, single leg balance, 4 hopping tasks (single, triple, crossover, and 6-meter timed hop), and a bilateral drop vertical jump that was scored with the Landing Error Scoring System (LESS). Peak torque, average torque, average power, total work, fatigue indices, center of pressure area and velocity, hop distance and time, and LESS score. A series of factor analyses were conducted to assess grouping of functional tests on the LEAP for each limb in the ACLR and healthy groups and limb symmetry indices (LSI) for both groups. Correlations were run between measures that loaded on retained factors. Isokinetic and isometric strength tests for knee flexion and extension, hopping, balance, and fatigue index were identified as unique factors for all limbs. The LESS score loaded with various factors across the different limbs. The healthy group LSI analysis produced more factors than the ACLR LSI analysis. Individual measures within each factor had moderate to strong correlations. Isokinetic and isometric strength, hopping, balance, and fatigue index provided unique information. Within each category of measures, not all tests may need to be included for a comprehensive functional assessment of ACLR patients due to the high amount of shared variance between them.

  16. Defining Cyberbullying.

    Science.gov (United States)

    Englander, Elizabeth; Donnerstein, Edward; Kowalski, Robin; Lin, Carolyn A; Parti, Katalin

    2017-11-01

    Is cyberbullying essentially the same as bullying, or is it a qualitatively different activity? The lack of a consensual, nuanced definition has limited the field's ability to examine these issues. Evidence suggests that being a perpetrator of one is related to being a perpetrator of the other; furthermore, strong relationships can also be noted between being a victim of either type of attack. It also seems that both types of social cruelty have a psychological impact, although the effects of being cyberbullied may be worse than those of being bullied in a traditional sense (evidence here is by no means definitive). A complicating factor is that the 3 characteristics that define bullying (intent, repetition, and power imbalance) do not always translate well into digital behaviors. Qualities specific to digital environments often render cyberbullying and bullying different in circumstances, motivations, and outcomes. To make significant progress in addressing cyberbullying, certain key research questions need to be addressed. These are as follows: How can we define, distinguish between, and understand the nature of cyberbullying and other forms of digital conflict and cruelty, including online harassment and sexual harassment? Once we have a functional taxonomy of the different types of digital cruelty, what are the short- and long-term effects of exposure to or participation in these social behaviors? What are the idiosyncratic characteristics of digital communication that users can be taught? Finally, how can we apply this information to develop and evaluate effective prevention programs? Copyright © 2017 by the American Academy of Pediatrics.

  17. Syntheses and Post-Polymerization Modifications of Well-Defined Styrenic Polymers Containing Three-Membered Heterocyclic Functionalities

    Science.gov (United States)

    McLeod, David Charles

    Macromolecules that contain electrophilic moieties, such as benzyl halides, activated esters, and epoxides, will readily undergo efficient nucleophilic substitution reactions with a wide variety of compounds under mild conditions, and are therefore ideally suited to act as "universal" precursors to functional materials. Epoxide-containing polymers derived from the radical polymerization of commercially-available glycidyl methacrylate are often employed in this role; however, methacrylic polymers suffer from certain limitations as a result of the incorporated ester groups, which are not stabile in the presence of strong nucleophiles, acids, bases, or esterase enzymes. Styrenic polymers that do not contain labile carbonyl moieties are usually the precursors of choice when high chemical stability is desired in the end product, but the production of functional materials from epoxide-containing styrenic polymers is relatively unexplored. In this dissertation, improved methods were developed for synthesizing 4-vinylphenyloxirane (4VPO) and 4-vinylphenyl glycidyl ether (4VPGE), two of the better-known epoxide-containing styrenic monomers, in high-yield and purity. Well-defined, epoxide-containing styrenic polymers with targeted molecular weights, narrow molecular weight distributions, and controlled architectures (specifically, linear and star-shaped homopolymers, as well as linear block copolymers with styrene) were produced from 4VPO and 4VPGE for the first time using reversible-deactivation radical polymerization techniques, such as low-catalyst-concentration atom transfer radical polymerization (LCC ATRP) and reversible addition-fragmentation chain-transfer (RAFT) polymerization. The robust nature and utility of poly4VPO and poly4VPGE were then demonstrated by the efficient, ring-opening modification of the pendant epoxide groups with a structurally- and functionally-diverse array of alcohols under acidic conditions at ambient temperature. The macromolecular

  18. The Ultimate Big Data Enterprise Initiative: Defining Functional Capabilities for an International Information System (IIS) for Orbital Space Data (OSD)

    Science.gov (United States)

    Raygan, R.

    Global collaboration in support of an International Information System (IIS) for Orbital Space Data (OSD) literally requires a global enterprise. As with many information technology enterprise initiatives attempting to coral the desires of business with the budgets and limitations of technology, Space Situational Awareness (SSA) includes many of the same challenges: 1) Adaptive / Intuitive Dash Board that facilitates User Experience Design for a variety of users. 2) Asset Management of hundreds of thousands of objects moving at thousands of miles per hour hundreds of miles in space. 3) Normalization and integration of diverse data in various languages, possibly hidden or protected from easy access. 4) Expectations of near real-time information availability coupled with predictive analysis to affect decisions before critical points of no return, such as Space Object Conjunction Assessment (CA). 5) Data Ownership, management, taxonomy, and accuracy. 6) Integrated metrics and easily modified algorithms for "what if" analysis. This paper proposes an approach to define the functional capabilities for an IIS for OSD. These functional capabilities not only address previously identified gaps in current systems but incorporate lessons learned from other big data, enterprise, and agile information technology initiatives that correlate to the space domain. Viewing the IIS as the "data service provider" allows adoption of existing information technology processes which strengthen governance and ensure service consumers certain levels of service dependability and accuracy.

  19. Theoretical study for a digital transfer function analyser; Etude theorique pour un transferometre digital

    Energy Technology Data Exchange (ETDEWEB)

    Freycenon, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    This study deals with the harmonic analysis of the instantaneous counting rate of a pulse train. This arises from using a fission chamber for reactivity to power transfer function measurements by oscillation methods in reactors. The systematical errors due to the sampling process are computed. The integration carried out when sampling the signal modifies the formulae of the Nyquist theorem on spectrum folding. The statistical errors due to the noise are analysed: it is shown that the bandwidth of the spectral window applied to the noise frequency spectrum is equal to the inverse of the time duration of the experiment. A dead time of 25 per cent of the sampling time does not increase appreciably the bandwidth. A new method is proposed afterwards yielding very approximate results of the Fourier analysis during the experiment. The systematical errors arising from the measuring process are determined, and it is shown that the bandwidth of the corresponding spectral window is still given by the inverse of the time duration of the experiment. (author) [French] Cette etude se rapporte a l'analyse harmonique de la valeur instantanee du taux de comptage d'une suite d'impulsions. On rencontre ce probleme dans l'utilisation de chambres a fission pour les mesures de fonction de transfert reactivite-puissance par la methode d'oscillation dans les piles. On calcule l'erreur systematique due au processus d'echantillonnage ou l'integration operee modifie les formules classiques de recouvrement du spectre. On analyse ensuite les erreurs statistiques dues au bruit de fond. On montre que la largeur de bande de la fenetre spectrale appliquee au spectre de puissance du bruit est donnee par l'inverse du temps de mesure. Un temps mort de 25 pour cent du temps de prelevement n'accroit pas sensiblement cette largeur de bande. On propose ensuite un procede simple qui permet d'obtenir, en cours d'experience, des resultats tres approches de l'analyse de Fourier. On determine les erreurs

  20. MeV gamma-ray observation with a well-defined point spread function based on electron tracking

    Science.gov (United States)

    Takada, A.; Tanimori, T.; Kubo, H.; Mizumoto, T.; Mizumura, Y.; Komura, S.; Kishimoto, T.; Takemura, T.; Yoshikawa, K.; Nakamasu, Y.; Matsuoka, Y.; Oda, M.; Miyamoto, S.; Sonoda, S.; Tomono, D.; Miuchi, K.; Kurosawa, S.; Sawano, T.

    2016-07-01

    The field of MeV gamma-ray astronomy has not opened up until recently owing to imaging difficulties. Compton telescopes and coded-aperture imaging cameras are used as conventional MeV gamma-ray telescopes; however their observations are obstructed by huge background, leading to uncertainty of the point spread function (PSF). Conventional MeV gamma-ray telescopes imaging utilize optimizing algorithms such as the ML-EM method, making it difficult to define the correct PSF, which is the uncertainty of a gamma-ray image on the celestial sphere. Recently, we have defined and evaluated the PSF of an electron-tracking Compton camera (ETCC) and a conventional Compton telescope, and thereby obtained an important result: The PSF strongly depends on the precision of the recoil direction of electron (scatter plane deviation, SPD) and is not equal to the angular resolution measure (ARM). Now, we are constructing a 30 cm-cubic ETCC for a second balloon experiment, Sub-MeV gamma ray Imaging Loaded-on-balloon Experiment: SMILE-II. The current ETCC has an effective area of 1 cm2 at 300 keV, a PSF of 10° at FWHM for 662 keV, and a large field of view of 3 sr. We will upgrade this ETCC to have an effective area of several cm2 and a PSF of 5° using a CF4-based gas. Using the upgraded ETCC, our observation plan for SMILE-II is to map of the electron-positron annihilation line and the 1.8 MeV line from 26Al. In this paper, we will report on the current performance of the ETCC and on our observation plan.

  1. Characterization of Aeromonas hydrophila wound pathotypes by comparative genomic and functional analyses of virulence genes.

    Science.gov (United States)

    Grim, Christopher J; Kozlova, Elena V; Sha, Jian; Fitts, Eric C; van Lier, Christina J; Kirtley, Michelle L; Joseph, Sandeep J; Read, Timothy D; Burd, Eileen M; Tall, Ben D; Joseph, Sam W; Horneman, Amy J; Chopra, Ashok K; Shak, Joshua R

    2013-04-23

    Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966(T), and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966(T). The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966(T) and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. Aeromonas hydrophila is a common aquatic bacterium that has increasingly been implicated in serious human infections. While many determinants of virulence have been identified in Aeromonas, rapid identification of pathogenic versus nonpathogenic

  2. Genome-wide identification and function analyses of heat shock transcription factors in potato

    Directory of Open Access Journals (Sweden)

    Ruimin eTang

    2016-04-01

    Full Text Available Heat shock transcription factors (Hsfs play vital roles in the regulation of tolerance to various stresses in living organisms. To dissect the mechanisms of the Hsfs in potato adaptation to abiotic stresses, genome and transcriptome analyses of Hsf gene family were investigated in Solanum tuberosum L. Twenty-seven StHsf members were identified by bioinformatics and phylogenetic analyses and were classified into A, B and C groups according to their structural and phylogenetic features. StHsfs in the same class shared similar gene structures and conserved motifs. The chromosomal location analysis showed that 27 Hsfs were located in 10 of 12 chromosomes (except chromosome 1 and chromosome 5 and that 18 of these genes formed 9 paralogous pairs. Expression profiles of StHsfs in 12 different organs and tissues uncovered distinct spatial expression patterns of these genes and their potential roles in the process of growth and development. Promoter and quantitative real-time polymerase chain reaction (qRT-PCR detections of StHsfs were conducted and demonstrated that these genes were all responsive to various stresses. StHsf004, StHsf007, StHsf009, StHsf014 and StHsf019 were constitutively expressed under non-stress conditions, and some specific Hsfs became the predominant Hsfs in response to different abiotic stresses, indicating their important and diverse regulatory roles in adverse conditions. A co-expression network between StHsfs and StHsf-co-expressed genes was generated based on the publicly-available potato transcriptomic databases and identified key candidate StHsfs for further functional studies.

  3. The practical impact of differential item functioning analyses in a health-related quality of life instrument

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

    2009-01-01

    Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results.......Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results....

  4. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Science.gov (United States)

    Kato, Kazuki; Ishii, Ryohei; Goto, Eiji; Ishitani, Ryuichiro; Tokunaga, Fuminori; Nureki, Osamu

    2013-01-01

    The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  5. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Directory of Open Access Journals (Sweden)

    Kazuki Kato

    Full Text Available The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING, resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  6. “Multi-Omics” Analyses of the Development and Function of Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yonggang Zhou

    2017-09-01

    Full Text Available For over four decades, our understanding of natural killer (NK cells has evolved from the original description of cluster of differentiation (CD56+CD3− to establishing NK cells as an important subset of innate lymphocytes in the host’s surveillance against viral infections and malignancy. The progress of research on the fundamental properties and therapeutic prospects for translational medicine using NK cells excites immunologists and clinicians. Over the past decade, numerous advances in “-omics”-scale methods and new technological approaches have addressed many essential questions in the biology of NK cells. We now have further understanding of the overall molecular mechanisms of action that determine the development, function, plasticity, diversity, and immune reactivity of NK cells. These findings are summarized here, and our view on how to study NK cells using “multi-omics” is highlighted. We also describe “-omics” analyses of the relationships between NK cells and viral infection, tumorigenesis, and autoimmune diseases. Ultimately, a deeper and more comprehensive understanding of NK cells in multiple conditions will provide more effective strategies to manipulate NK cells for the treatment of human disease.

  7. Analysis of C. elegans NR2E nuclear receptors defines three conserved clades and ligand-independent functions

    Directory of Open Access Journals (Sweden)

    Weber Katherine P

    2012-06-01

    Full Text Available Abstract Background The nuclear receptors (NRs are an important class of transcription factors that are conserved across animal phyla. Canonical NRs consist of a DNA-binding domain (DBD and ligand-binding domain (LBD. While most animals have 20–40 NRs, nematodes of the genus Caenorhabditis have experienced a spectacular proliferation and divergence of NR genes. The LBDs of evolutionarily-conserved Caenorhabditis NRs have diverged sharply from their Drosophila and vertebrate orthologs, while the DBDs have been strongly conserved. The NR2E family of NRs play critical roles in development, especially in the nervous system. In this study, we explore the phylogenetics and function of the NR2E family of Caenorhabditis elegans, using an in vivo assay to test LBD function. Results Phylogenetic analysis reveals that the NR2E family of NRs consists of three broadly-conserved clades of orthologous NRs. In C. elegans, these clades are defined by nhr-67, fax-1 and nhr-239. The vertebrate orthologs of nhr-67 and fax-1 are Tlx and PNR, respectively. While the nhr-239 clade includes orthologs in insects (Hr83, an echinoderm, and a hemichordate, the gene appears to have been lost from vertebrate lineages. The C. elegans and C. briggsae nhr-239 genes have an apparently-truncated and highly-diverged LBD region. An additional C. elegans NR2E gene, nhr-111, appears to be a recently-evolved paralog of fax-1; it is present in C. elegans, but not C. briggsae or other animals with completely-sequenced genomes. Analysis of the relatively unstudied nhr-111 and nhr-239 genes demonstrates that they are both expressed—nhr-111 very broadly and nhr-239 in a small subset of neurons. Analysis of the FAX-1 LBD in an in vivo assay revealed that it is not required for at least some developmental functions. Conclusions Our analysis supports three conserved clades of NR2E receptors, only two of which are represented in vertebrates, indicating three ancestral NR2E genes in the

  8. Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma

    International Nuclear Information System (INIS)

    Beumer, Jan H.; Fu, Katherine Y.; Anyang, Bean N.; Siegfried, Jill M.; Bakkenist, Christopher J.

    2015-01-01

    ATM and ATR are kinases implicated in a myriad of DNA-damage responses. ATM kinase inhibition radiosensitizes cells and selectively kills cells with Fanconi anemia (FA) gene mutations. ATR kinase inhibition sensitizes cells to agents that induce replication stress and selectively kills cells with ATM and TP53 mutations. ATM mutations and FANCF promoter-methylation are reported in lung carcinomas. We undertook functional analyses of ATM, ATR, Chk1 and FA proteins in lung cancer cell lines. We included Calu6 that is reported to be FANCL-deficient. In addition, the cancer genome atlas (TCGA) database was interrogated for alterations in: 1) ATM, MRE11A, RAD50 and NBN; 2) ATR, ATRIP and TOPBP1; and 3) 15 FA genes. No defects in ATM, ATR or Chk1 kinase activation, or FANCD2 monoubiquitination were identified in the lung cancer cell lines examined, including Calu6, and major alterations in these pathways were not identified in the TCGA database. Cell lines were radiosensitized by ATM kinase inhibitor KU60019, but no cell killing by ATM kinase inhibitor alone was observed. While no synergy between gemcitabine or carboplatin and ATR kinase inhibitor ETP-46464 was observed, synergy between gemcitabine and Chk1 kinase inhibitor UCN-01 was observed in 54 T, 201 T and H460, and synergy between carboplatin and Chk1 kinase inhibitor was identified in 201 T and 239 T. No interactions between ATM, ATR and FA activation were observed by either ATM or ATR kinase inhibition in the lung cancer cell lines. Analyses of ATM serine 1981 and Chk1 serine 345 phosphorylation, and FANCD2 monoubiquitination revealed that ATM and ATR kinase activation and FA pathway signaling are intact in the lung cancer cell lines examined. As such, these posttranslational modifications may have utility as biomarkers for the integrity of DNA damage signaling pathways in lung cancer. Different sensitization profiles between gemcitabine and carboplatin and ATR kinase inhibitor ETP-46464 and Chk1 kinase inhibitor

  9. Analytical study of the effects of soft tissue artefacts on functional techniques to define axes of rotation.

    Science.gov (United States)

    De Rosario, Helios; Page, Álvaro; Besa, Antonio

    2017-09-06

    The accurate location of the main axes of rotation (AoR) is a crucial step in many applications of human movement analysis. There are different formal methods to determine the direction and position of the AoR, whose performance varies across studies, depending on the pose and the source of errors. Most methods are based on minimizing squared differences between observed and modelled marker positions or rigid motion parameters, implicitly assuming independent and uncorrelated errors, but the largest error usually results from soft tissue artefacts (STA), which do not have such statistical properties and are not effectively cancelled out by such methods. However, with adequate methods it is possible to assume that STA only account for a small fraction of the observed motion and to obtain explicit formulas through differential analysis that relate STA components to the resulting errors in AoR parameters. In this paper such formulas are derived for three different functional calibration techniques (Geometric Fitting, mean Finite Helical Axis, and SARA), to explain why each technique behaves differently from the others, and to propose strategies to compensate for those errors. These techniques were tested with published data from a sit-to-stand activity, where the true axis was defined using bi-planar fluoroscopy. All the methods were able to estimate the direction of the AoR with an error of less than 5°, whereas there were errors in the location of the axis of 30-40mm. Such location errors could be reduced to less than 17mm by the methods based on equations that use rigid motion parameters (mean Finite Helical Axis, SARA) when the translation component was calculated using the three markers nearest to the axis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity.

    Directory of Open Access Journals (Sweden)

    Li Jia

    Full Text Available The androgen receptor (AR is a steroid-activated transcription factor that binds at specific DNA locations and plays a key role in the etiology of prostate cancer. While numerous studies have identified a clear connection between AR binding and expression of target genes for a limited number of loci, high-throughput elucidation of these sites allows for a deeper understanding of the complexities of this process.We have mapped 189 AR occupied regions (ARORs and 1,388 histone H3 acetylation (AcH3 loci to a 3% continuous stretch of human genomic DNA using chromatin immunoprecipitation (ChIP microarray analysis. Of 62 highly reproducible ARORs, 32 (52% were also marked by AcH3. While the number of ARORs detected in prostate cancer cells exceeded the number of nearby DHT-responsive genes, the AcH3 mark defined a subclass of ARORs much more highly associated with such genes -- 12% of the genes flanking AcH3+ARORs were DHT-responsive, compared to only 1% of genes flanking AcH3-ARORs. Most ARORs contained enhancer activities as detected in luciferase reporter assays. Analysis of the AROR sequences, followed by site-directed ChIP, identified binding sites for AR transcriptional coregulators FoxA1, CEBPbeta, NFI and GATA2, which had diverse effects on endogenous AR target gene expression levels in siRNA knockout experiments.We suggest that only some ARORs function under the given physiological conditions, utilizing diverse mechanisms. This diversity points to differential regulation of gene expression by the same transcription factor related to the chromatin structure.

  11. Well-Defined Bilayered Molecular Cobrushes with Internal Polyethylene Blocks and ω-Hydroxyl-Functionalized Polyethylene Homobrushes

    KAUST Repository

    Zhang, Hefeng; Hadjichristidis, Nikolaos

    2016-01-01

    Novel well-defined bilayered molecular cobrushes with internal polyethylene blocks, P(PEcore-b-PScorona) (PE: polyethylene; PS: polystyrene), and ω-hydroxyl-functionalized polyethylene homobrushes, P(PE-OH), were synthesized through the macromonomer strategy. Two main steps were involved in the synthesis of the P(PEcore-b-PScorona) bilayered cobrushes: (i) formation of norbornyl-terminated macromonomer (Nor-PE-b-PS) by esterification of PS-b-PE-OH (combination of anionic polymerization, hydroboration, and polyhomologation) with 5-norbornene-2-carboxylic acid and (ii) ring-opening metathesis polymerization (ROMP) of Nor-PE-b-PS. The synthesis of P(PE-OH) was achieved by (i) hydroboration of tert-butyldimethylsilyl-protected allyl alcohol, followed by polyhomologation of dimethylsulfoxoniun methylide with the formed tri[3-(tert-butyldimethylsilyloxyl)propyl]borane initiator, oxidation/hydrolysis, and esterification of the TBDMS-O-PE-OH with 5-norbornene-2-carboxylic acid to afford the macromonomer TBDMS-O-PE-Nor, and (ii) ROMP of TBDMS-O-PE-Nor, followed by deprotection. Nuclear magnetic resonance spectroscopy (1H and 13C NMR) and high temperature gel permeation chromatography (HT-GPC) were used to characterize all macromonomers/molecular brushes and differential scanning calorimetry (DSC) to study the thermal properties. The molecular brush P(PE-b-PS) showed lower melting point (Tm) and better solubility in toluene than the corresponding macromonomer PS-b-PE-Nor. In the case of homobrushes, the thermal properties were strongly affected by the presence of the PE end-groups. © 2016 American Chemical Society.

  12. Well-Defined Bilayered Molecular Cobrushes with Internal Polyethylene Blocks and ω-Hydroxyl-Functionalized Polyethylene Homobrushes

    KAUST Repository

    Zhang, Hefeng

    2016-02-15

    Novel well-defined bilayered molecular cobrushes with internal polyethylene blocks, P(PEcore-b-PScorona) (PE: polyethylene; PS: polystyrene), and ω-hydroxyl-functionalized polyethylene homobrushes, P(PE-OH), were synthesized through the macromonomer strategy. Two main steps were involved in the synthesis of the P(PEcore-b-PScorona) bilayered cobrushes: (i) formation of norbornyl-terminated macromonomer (Nor-PE-b-PS) by esterification of PS-b-PE-OH (combination of anionic polymerization, hydroboration, and polyhomologation) with 5-norbornene-2-carboxylic acid and (ii) ring-opening metathesis polymerization (ROMP) of Nor-PE-b-PS. The synthesis of P(PE-OH) was achieved by (i) hydroboration of tert-butyldimethylsilyl-protected allyl alcohol, followed by polyhomologation of dimethylsulfoxoniun methylide with the formed tri[3-(tert-butyldimethylsilyloxyl)propyl]borane initiator, oxidation/hydrolysis, and esterification of the TBDMS-O-PE-OH with 5-norbornene-2-carboxylic acid to afford the macromonomer TBDMS-O-PE-Nor, and (ii) ROMP of TBDMS-O-PE-Nor, followed by deprotection. Nuclear magnetic resonance spectroscopy (1H and 13C NMR) and high temperature gel permeation chromatography (HT-GPC) were used to characterize all macromonomers/molecular brushes and differential scanning calorimetry (DSC) to study the thermal properties. The molecular brush P(PE-b-PS) showed lower melting point (Tm) and better solubility in toluene than the corresponding macromonomer PS-b-PE-Nor. In the case of homobrushes, the thermal properties were strongly affected by the presence of the PE end-groups. © 2016 American Chemical Society.

  13. Function and significance of bell beaker pottery according to data from residue analyses

    Directory of Open Access Journals (Sweden)

    Guerra Doce, Elisa

    2006-06-01

    Full Text Available Traditionally, Bell Beakers have been thought to contain alcoholic beverages which were consumed in the course of male feasting ceremonies. Recent residue analyses have shed some light on the question of their function. However, whilst beer and mead have been identified from certain examples, not all Beakers were drinking cups. Some were used as reduction pots to smelt copper ores, others have some organic residues associated with food, and still others were employed as funerary urns. Yet, while the evidence points to a diversity of uses, it is argued that an ideological connection can be observed. Beakers were probably a special form of pottery with a ritual character, related to activities that imply some kind of transformation.

    Los vasos campaniformes suelen relacionarse con el consumo de bebidas alcohólicas durante la celebración de banquetes ceremoniales de exaltación masculina. Si bien las analíticas de residuos han identificado cerveza e hidromiel en unos cuantos ejemplares, no todos los campaniformes desempeñaron esta misma función. Algunos hicieron las veces de vasijas-horno para reducir el mineral de cobre, en otros se han detectado restos de alimentos y también se emplearon como urnas funerarias. A pesar de esta diversidad de usos, creemos que existe una conexión ideológica entre ellos, de tal manera que habría que considerar a los campaniformes como una cerámica singular con un carácter ritual, destinada a actividades que conllevan algún tipo de transformación.

  14. Functional assays and metagenomic analyses reveals differences between the microbial communities inhabiting the soil horizons of a Norway spruce plantation.

    Directory of Open Access Journals (Sweden)

    Stéphane Uroz

    Full Text Available In temperate ecosystems, acidic forest soils are among the most nutrient-poor terrestrial environments. In this context, the long-term differentiation of the forest soils into horizons may impact the assembly and the functions of the soil microbial communities. To gain a more comprehensive understanding of the ecology and functional potentials of these microbial communities, a suite of analyses including comparative metagenomics was applied on independent soil samples from a spruce plantation (Breuil-Chenue, France. The objectives were to assess whether the decreasing nutrient bioavailability and pH variations that naturally occurs between the organic and mineral horizons affects the soil microbial functional biodiversity. The 14 Gbp of pyrosequencing and Illumina sequences generated in this study revealed complex microbial communities dominated by bacteria. Detailed analyses showed that the organic soil horizon was significantly enriched in sequences related to Bacteria, Chordata, Arthropoda and Ascomycota. On the contrary the mineral horizon was significantly enriched in sequences related to Archaea. Our analyses also highlighted that the microbial communities inhabiting the two soil horizons differed significantly in their functional potentials according to functional assays and MG-RAST analyses, suggesting a functional specialisation of these microbial communities. Consistent with this specialisation, our shotgun metagenomic approach revealed a significant increase in the relative abundance of sequences related glycoside hydrolases in the organic horizon compared to the mineral horizon that was significantly enriched in glycoside transferases. This functional stratification according to the soil horizon was also confirmed by a significant correlation between the functional assays performed in this study and the functional metagenomic analyses. Together, our results suggest that the soil stratification and particularly the soil resource

  15. No effects of functional exercise therapy on walking biomechanics in patients with knee osteoarthritis: exploratory outcome analyses from a randomised trial.

    Science.gov (United States)

    Henriksen, Marius; Klokker, Louise; Bartholdy, Cecilie; Schjoedt-Jorgensen, Tanja; Bandak, Elisabeth; Bliddal, Henning

    2016-01-01

    To assess the effects of a functional and individualised exercise programme on gait biomechanics during walking in people with knee OA. Sixty participants were randomised to 12 weeks of facility-based functional and individualised neuromuscular exercise therapy (ET), 3 sessions per week supervised by trained physical therapists, or a no attention control group (CG). Three-dimensional gait analyses were used, from which a comprehensive list of conventional gait variables were extracted (totally 52 kinematic, kinetic and spatiotemporal variables). According to the protocol, the analyses were based on the 'Per-Protocol' population (defined as participants following the protocol with complete and valid gait analyses). Analysis of covariance adjusting for the level at baseline was used to determine differences between groups (95% CIs) in the changes from baseline at follow-up. The per-protocol population included 46 participants (24 ET/22 CG). There were no group differences in the analysed gait variables, except for a significant group difference in the second peak knee flexor moment and second peak vertical ground reaction force. While plausible we have limited confidence in the findings due to multiple statistical tests and lack of biomechanical logics. Therefore we conclude that a 12-week supervised individualised neuromuscular exercise programme has no effects on gait biomechanics. Future studies should focus on exercise programmes specifically designed to alter gait patterns, or include other measures of mobility, such as walking on stairs or inclined surfaces. ClinicalTrials.gov: NCT01545258.

  16. Effects of Computer-Based Training on Procedural Modifications to Standard Functional Analyses

    Science.gov (United States)

    Schnell, Lauren K.; Sidener, Tina M.; DeBar, Ruth M.; Vladescu, Jason C.; Kahng, SungWoo

    2018-01-01

    Few studies have evaluated methods for training decision-making when functional analysis data are undifferentiated. The current study evaluated computer-based training to teach 20 graduate students to arrange functional analysis conditions, analyze functional analysis data, and implement procedural modifications. Participants were exposed to…

  17. Vorschlag zur Erarbeitung einer operationalen Fremdwortdefinition (A Proposal for Establishing a Functional System for Defining Foreign Words)

    Science.gov (United States)

    Schank, Gerd

    1974-01-01

    In order to define words borrowed from other languages, dialects or varieties within a dialect, a synchronic definition, including the degree of integration into the borrowing language, is more useful and flexible than the traditional etymological approach. (Text is in German.) (TL)

  18. Metagenomic and functional analyses of the consequences of reduction of bacterial diversity on soil functions and bioremediation in diesel-contaminated microcosms

    OpenAIRE

    Jung, Jaejoon; Philippot, Laurent

    2016-01-01

    The relationship between microbial biodiversity and soil function is an important issue in ecology, yet most studies have been performed in pristine ecosystems. Here, we assess the role of microbial diversity in ecological function and remediation strategies in diesel-contaminated soils. Soil microbial diversity was manipulated using a removal by dilution approach and microbial functions were determined using both metagenomic analyses and enzymatic assays. A shift from Proteobacteria- to Acti...

  19. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  20. 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

  1. Evaluating the Accuracy of Results for Teacher Implemented Trial-Based Functional Analyses.

    Science.gov (United States)

    Rispoli, Mandy; Ninci, Jennifer; Burke, Mack D; Zaini, Samar; Hatton, Heather; Sanchez, Lisa

    2015-09-01

    Trial-based functional analysis (TBFA) allows for the systematic and experimental assessment of challenging behavior in applied settings. The purposes of this study were to evaluate a professional development package focused on training three Head Start teachers to conduct TBFAs with fidelity during ongoing classroom routines. To assess the accuracy of the TBFA results, the effects of a function-based intervention derived from the TBFA were compared with the effects of a non-function-based intervention. Data were collected on child challenging behavior and appropriate communication. An A-B-A-C-D design was utilized in which A represented baseline, and B and C consisted of either function-based or non-function-based interventions counterbalanced across participants, and D represented teacher implementation of the most effective intervention. Results showed that the function-based intervention produced greater decreases in challenging behavior and greater increases in appropriate communication than the non-function-based intervention for all three children. © The Author(s) 2015.

  2. Comparative analyses identified species-specific functional roles in oral microbial genomes

    Science.gov (United States)

    Chen, Tsute; Gajare, Prasad; Olsen, Ingar; Dewhirst, Floyd E.

    2017-01-01

    ABSTRACT The advent of next generation sequencing is producing more genomic sequences for various strains of many human oral microbial species and allows for insightful functional comparisons at both intra- and inter-species levels. This study performed in-silico functional comparisons for currently available genomic sequences of major species associated with periodontitis including Aggregatibacter actinomycetemcomitans (AA), Porphyromonas gingivalis (PG), Treponema denticola (TD), and Tannerella forsythia (TF), as well as several cariogenic and commensal streptococcal species. Complete or draft sequences were annotated with the RAST to infer structured functional subsystems for each genome. The subsystems profiles were clustered to groups of functions with similar patterns. Functional enrichment and depletion were evaluated based on hypergeometric distribution to identify subsystems that are unique or missing between two groups of genomes. Unique or missing metabolic pathways and biological functions were identified in different species. For example, components involved in flagellar motility were found only in the motile species TD, as expected, with few exceptions scattered in several streptococcal species, likely associated with chemotaxis. Transposable elements were only found in the two Bacteroidales species PG and TF, and half of the AA genomes. Genes involved in CRISPR were prevalent in most oral species. Furthermore, prophage related subsystems were also commonly found in most species except for PG and Streptococcus mutans, in which very few genomes contain prophage components. Comparisons between pathogenic (P) and nonpathogenic (NP) genomes also identified genes potentially important for virulence. Two such comparisons were performed between AA (P) and several A. aphrophilus (NP) strains, and between S. mutans + S. sobrinus (P) and other oral streptococcal species (NP). This comparative genomics approach can be readily used to identify functions unique to

  3. End-systolic stress-velocity relation and circumferential fiber velocity shortening for analysing left ventricular function in mice

    Energy Technology Data Exchange (ETDEWEB)

    Fayssoil, A. [Cardiologie, Hopital europeen Georges Pompidou, 20, rue le blanc, Paris (France)], E-mail: fayssoil2000@yahoo.fr; Renault, G. [CNRS UMR 8104, Inserm, U567, Institut Cochin, Universite Paris Descartes, Paris (France); Fougerousse, F. [Genethon, RD, Evry (France)

    2009-08-15

    Traditionally, analysing left ventricular (LV) performance relies on echocardiography by evaluating shortening fraction (SF) in mice. SF is influenced by load conditions. End-systolic stress-velocity (ESSV) relation and circumferential fiber velocity (VcF) shortening are more relevant parameters for evaluating systolic function regardless load conditions particularly in mice's models of heart failure.

  4. Sum rule and hydrodynamic analyses of the velocity autocorrelation function in strongly coupled plasmas

    International Nuclear Information System (INIS)

    Nagano, Seido; Ichimaru, Setsuo

    1980-01-01

    The memory function for the velocity autocorrelation function in a strongly coupled, one-component plasma is analyzed in the short time and long time domains, respectively, with the aid of the frequency-moment sum rules and the hydrodynamic consideration evoking the idea of the generalized Stokes friction. A series of interpolation schemes with successively improved accuracies are then introduced. Numerical investigations of those interpolation schemes clarify the physical origin of the three different types of the velocity autocorrelation function observed in the molecular dynamics simulation at different regimes of the coupling constant. (author)

  5. Define Project

    DEFF Research Database (Denmark)

    Munk-Madsen, Andreas

    2005-01-01

    "Project" is a key concept in IS management. The word is frequently used in textbooks and standards. Yet we seldom find a precise definition of the concept. This paper discusses how to define the concept of a project. The proposed definition covers both heavily formalized projects and informally...... organized, agile projects. Based on the proposed definition popular existing definitions are discussed....

  6. "Dermatitis" defined.

    Science.gov (United States)

    Smith, Suzanne M; Nedorost, Susan T

    2010-01-01

    The term "dermatitis" can be defined narrowly or broadly, clinically or histologically. A common and costly condition, dermatitis is underresourced compared to other chronic skin conditions. The lack of a collectively understood definition of dermatitis and its subcategories could be the primary barrier. To investigate how dermatologists define the term "dermatitis" and determine if a consensus on the definition of this term and other related terms exists. A seven-question survey of dermatologists nationwide was conducted. Of respondents (n  =  122), half consider dermatitis to be any inflammation of the skin. Nearly half (47.5%) use the term interchangeably with "eczema." Virtually all (> 96%) endorse the subcategory "atopic" under the terms "dermatitis" and "eczema," but the subcategories "contact," "drug hypersensitivity," and "occupational" are more highly endorsed under the term "dermatitis" than under the term "eczema." Over half (55.7%) personally consider "dermatitis" to have a broad meaning, and even more (62.3%) believe that dermatologists as a whole define the term broadly. There is a lack of consensus among experts in defining dermatitis, eczema, and their related subcategories.

  7. Towards spatially smart abatement of human pharmaceuticals in surface waters: defining impact of sewage treatment plants on susceptible functions

    NARCIS (Netherlands)

    Gils, J.A.G.; Coppens, L.J.C.; Laak, ter T.L.; Raterman, B.W.; Wezel, van A.P.

    2015-01-01

    For human pharmaceuticals, sewage treatment plants (STPs) are a major point of entry to surface waters. The receiving waters provide vital functions. Modeling the impact of STPs on susceptible functions of the surface water system allows for a spatially smart implementation of abatement options at,

  8. Towards spatially smart abatement of human pharmaceuticals in surface waters : Defining impact of sewage treatment plants on susceptible functions

    NARCIS (Netherlands)

    Coppens, Lieke J C; van Gils, Jos A G; Ter Laak, Thomas L|info:eu-repo/dai/nl/304831026; Raterman, Bernard W; van Wezel, Annemarie P|info:eu-repo/dai/nl/141376074

    2015-01-01

    For human pharmaceuticals, sewage treatment plants (STPs) are a major point of entry to surface waters. The receiving waters provide vital functions. Modeling the impact of STPs on susceptible functions of the surface water system allows for a spatially smart implementation of abatement options at,

  9. An Innovative Approach to Functionality Testing of Analysers in the Clinical Laboratory

    OpenAIRE

    Stockmann, Wolfgang; Engeldinger, Werner; Kunst, Albert; McGovern, Margaret

    2008-01-01

    The established protocols for evaluating new analytical systems produce indispensable information with regard to quality characteristics, but in general they fail to analyse the system performance under routine-like conditions. We describe a model which allows the testing of a new analytical system under conditions close to the routine in a controlled and systematic manner by using an appropriate software tool. Performing routine simulation experiments, either reflecting imprecision or method...

  10. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus.

    Directory of Open Access Journals (Sweden)

    Weiwei Lei

    Full Text Available Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in

  11. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus).

    Science.gov (United States)

    Lei, Weiwei; Ravoninjohary, Aurore; Li, Xia; Margolskee, Robert F; Reed, Danielle R; Beauchamp, Gary K; Jiang, Peihua

    2015-01-01

    Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor) genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus) should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in understanding the forces

  12. Comparative Analyses of Aryl Hydrocarbon Receptor Structure, Function, and Evolution in Marine Mammals

    Science.gov (United States)

    2007-02-01

    function in early vertebrates: inducibility of cytochrome P450 1A in agnathan and elasmobranch fish . Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 120...J.Y., A.G. McArthur and J.J. Stegeman. 2005b. Characterization of a cetacean aromatase (CYP19) and the phylogeny and functional conservation of... phylogeny of cetaceans prompts revision of morphological transformations. Trends in Ecology and Evolution 10:328-334. Nei, M., P. Xu and G. Glazko

  13. Cross-biome metagenomic analyses of soil microbial communities and their functional attributes.

    Science.gov (United States)

    Fierer, Noah; Leff, Jonathan W; Adams, Byron J; Nielsen, Uffe N; Bates, Scott Thomas; Lauber, Christian L; Owens, Sarah; Gilbert, Jack A; Wall, Diana H; Caporaso, J Gregory

    2012-12-26

    For centuries ecologists have studied how the diversity and functional traits of plant and animal communities vary across biomes. In contrast, we have only just begun exploring similar questions for soil microbial communities despite soil microbes being the dominant engines of biogeochemical cycles and a major pool of living biomass in terrestrial ecosystems. We used metagenomic sequencing to compare the composition and functional attributes of 16 soil microbial communities collected from cold deserts, hot deserts, forests, grasslands, and tundra. Those communities found in plant-free cold desert soils typically had the lowest levels of functional diversity (diversity of protein-coding gene categories) and the lowest levels of phylogenetic and taxonomic diversity. Across all soils, functional beta diversity was strongly correlated with taxonomic and phylogenetic beta diversity; the desert microbial communities were clearly distinct from the nondesert communities regardless of the metric used. The desert communities had higher relative abundances of genes associated with osmoregulation and dormancy, but lower relative abundances of genes associated with nutrient cycling and the catabolism of plant-derived organic compounds. Antibiotic resistance genes were consistently threefold less abundant in the desert soils than in the nondesert soils, suggesting that abiotic conditions, not competitive interactions, are more important in shaping the desert microbial communities. As the most comprehensive survey of soil taxonomic, phylogenetic, and functional diversity to date, this study demonstrates that metagenomic approaches can be used to build a predictive understanding of how microbial diversity and function vary across terrestrial biomes.

  14. Inter-areal causal interactions in the gamma and beta frequency bands define a functional hierarchy in the primate visual system

    NARCIS (Netherlands)

    Vezoli, J.; Bastos, A.; Bosman, C.; Schoffelen, J.M.; Oostenveld, R.; Weerd, P. De; Kennedy, H.; Fries, P.

    2013-01-01

    Cortico-cortical connectivity has been shown to be hierarchically organized such that bottom-up and top-down information are conveyed through the well-defined feedforward and feedback counter-streams, respectively. It remains however unclear what mechanisms the cortex might use to functionally

  15. Analysing innovation policy indicators through a functional approach: the aeronautic industry case

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, C.R.; Uriona Maldonado, M.

    2016-07-01

    Developing countries face different problems than developed countries and the use of the same indicator to evaluate and compare both regions can lead to misleading conclusions. Traditional indicators, such as R&D and patents may not capture the whole dynamic of a system, as they are used to compare systems focusing on its current structure. Many authors have been discussing the processes underlying industry transformation, innovation, and economic growth to access a system performance, i.e. the functions of innovation systems. Therefore, the purpose of this paper is to analyze these functions as indicators to measure the performance of the system in order to identify policy issues. In order to do that, we analyze the case of the aeronautic sectoral system of innovation of a region in Brazil. The functional approach helped us to better capture the dynamic of the system, by not restricting our analysis to the system’s structure. (Author)

  16. Analyses of functional brain connectivity; Untersuchungen zur funktionellen Konnektivitaet des Gehirns

    Energy Technology Data Exchange (ETDEWEB)

    Stephan, K.E.

    2003-03-01

    This dissertation includes two independent studies that investigate two complementary aspects of functional connectivity in the Macaque and the human brain. In the first study, a computational meta-analysis of published electrophysiological data on context-independent functional brain connectivity was conducted by means of three independent methods. The second study investigated the effects of the atypical antipsychotic substance olanzapine on the functional connectivity of the cerebellum during a simple motor task (self-paced finger tapping). Six schizophrenic patients and six control subjects matched for age and sex were investigated by functional magnetic resonance imaging (fMRI) twice. This study provided the first experimental data on the effects of atypical antipsychotic agents on functional brain connectivity and demonstrated pronounced olanzapine-dependent changes of functional couplings between cerebellum, thalamus, and prefrontal cortex. (orig.) [German] In der hier vorgelegten Arbeit werden zwei komplementaere Aspekte der funktionellen Konnektivitaet - im Gehirn des Makaken und Menschen anhand zweier separater Studien untersucht. In der ersten Studie wurde mittels dreier unabhaengiger Methoden eine Metaanalyse publizierter elektrophysiologischer Daten zur kontextunabhaengigen funktionellen Konnektivitaet des Makakenkortex durchgefuehrt. Diese Studie erbrachte damit zum ersten Mal den Nachweis einer funktionellen Small World-Netzwerkstruktur des Primatenkortex. In der zweiten Studie wurde der Effekt des atypischen Neuroleptikums Olanzapin auf die funktionelle Konnektivitaet des Zerebellums im Kontext einer einfachen motorischen Aufgabe (selbstgesteuertes Fingertrapping) untersucht. Sechs schizophrene Patienten, die Neuroleptika-naiv bzw. -entwoehnt waren, sowie sechs alters- und geschlechtsentprechende Kontrollprobanden wurden im Abstand von jeweils drei Wochen mit funktioneller Magnetresonanztomografie (fMRT) untersucht. Diese Studie lieferte die ersten

  17. The contribution of town functions to the development of rural areas: empirical analyses for Ethiopia

    NARCIS (Netherlands)

    Tadesse Woeldesenbet, T.

    2012-01-01

    Rural areas in many developing countries often lack infrastructure and institutions. However, rural towns and towns possess some of the major services that rural and town households can use to advance their economic activities. The study of the contribution that towns and their functions make to

  18. Analyses of soil microbial community compositions and functional genes reveal potential consequences of natural forest succession.

    Science.gov (United States)

    Cong, Jing; Yang, Yunfeng; Liu, Xueduan; Lu, Hui; Liu, Xiao; Zhou, Jizhong; Li, Diqiang; Yin, Huaqun; Ding, Junjun; Zhang, Yuguang

    2015-05-06

    The succession of microbial community structure and function is a central ecological topic, as microbes drive the Earth's biogeochemical cycles. To elucidate the response and mechanistic underpinnings of soil microbial community structure and metabolic potential relevant to natural forest succession, we compared soil microbial communities from three adjacent natural forests: a coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf forest (DBF) on Shennongjia Mountain in central China. In contrary to plant communities, the microbial taxonomic diversity of the DBF was significantly (P the DBF. Furthermore, a network analysis of microbial carbon and nitrogen cycling genes showed the network for the DBF samples was relatively large and tight, revealing strong couplings between microbes. Soil temperature, reflective of climate regimes, was important in shaping microbial communities at both taxonomic and functional gene levels. As a first glimpse of both the taxonomic and functional compositions of soil microbial communities, our results suggest that microbial community structure and function potentials will be altered by future environmental changes, which have implications for forest succession.

  19. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise...

  20. Flexible gateway constructs for functional analyses of genes in plant pathogenic fungi

    NARCIS (Netherlands)

    Mehrabi, Rahim; Mirzadi Gohari, Amir; Silva, da Gilvan Ferreira; Steinberg, Gero; Kema, Gert H.J.; Wit, de Pierre J.G.M.

    2015-01-01

    Genetic manipulation of fungi requires quick, low-cost, efficient, high-throughput and molecular tools. In this paper, we report 22 entry constructs as new molecular tools based on the Gateway technology facilitating rapid construction of binary vectors that can be used for functional analysis of

  1. Replicated landscape genetic and network analyses reveal wide variation in functional connectivity for American pikas.

    Science.gov (United States)

    Castillo, Jessica A; Epps, Clinton W; Jeffress, Mackenzie R; Ray, Chris; Rodhouse, Thomas J; Schwalm, Donelle

    2016-09-01

    Landscape connectivity is essential for maintaining viable populations, particularly for species restricted to fragmented habitats or naturally arrayed in metapopulations and facing rapid climate change. The importance of assessing both structural connectivity (physical distribution of favorable habitat patches) and functional connectivity (how species move among habitat patches) for managing such species is well understood. However, the degree to which functional connectivity for a species varies among landscapes, and the resulting implications for conservation, have rarely been assessed. We used a landscape genetics approach to evaluate resistance to gene flow and, thus, to determine how landscape and climate-related variables influence gene flow for American pikas (Ochotona princeps) in eight federally managed sites in the western United States. We used empirically derived, individual-based landscape resistance models in conjunction with predictive occupancy models to generate patch-based network models describing functional landscape connectivity. Metareplication across landscapes enabled identification of limiting factors for dispersal that would not otherwise have been apparent. Despite the cool microclimates characteristic of pika habitat, south-facing aspects consistently represented higher resistance to movement, supporting the previous hypothesis that exposure to relatively high temperatures may limit dispersal in American pikas. We found that other barriers to dispersal included areas with a high degree of topographic relief, such as cliffs and ravines, as well as streams and distances greater than 1-4 km depending on the site. Using the empirically derived network models of habitat patch connectivity, we identified habitat patches that were likely disproportionately important for maintaining functional connectivity, areas in which habitat appeared fragmented, and locations that could be targeted for management actions to improve functional connectivity

  2. Multistable Microactuators Functioning on the Basis of Electromagnetic Lorentz Force: Nonlinear Structural and Electrothermal Analyses

    International Nuclear Information System (INIS)

    Han, Jeong Sam

    2010-01-01

    In this paper, the design and nonlinear simulation of a multistable electromagnetic microactuator, which provides four stable equilibrium positions within its operating range, have been discussed. Quadstable actuator motion has been made possible by using both X- and Y-directional bistable structures with snapping curved beams. Two pairs of the curved beams are attached to an inner frame in both X- and Y-directions to realize independent bistable behavior in each direction. For the actuation of the actuator at the micrometer scale, an electromagnetic actuation method in which Lorentz force is taken into consideration was used. By using this method, micrometer-stroke quadstability in a plane parallel to a substrate was possible. The feasibility of designing an actuator that can realize quadstable motion by using the electromagnetic actuation method has been thoroughly clarified by performing nonlinear static and dynamic analyses and electrothermal coupled-field analysis of the multistable microactuator

  3. Overview of a surface-ripened cheese community functioning by meta-omics analyses.

    Directory of Open Access Journals (Sweden)

    Eric Dugat-Bony

    Full Text Available Cheese ripening is a complex biochemical process driven by microbial communities composed of both eukaryotes and prokaryotes. Surface-ripened cheeses are widely consumed all over the world and are appreciated for their characteristic flavor. Microbial community composition has been studied for a long time on surface-ripened cheeses, but only limited knowledge has been acquired about its in situ metabolic activities. We applied metagenomic, metatranscriptomic and biochemical analyses to an experimental surface-ripened cheese composed of nine microbial species during four weeks of ripening. By combining all of the data, we were able to obtain an overview of the cheese maturation process and to better understand the metabolic activities of the different community members and their possible interactions. Furthermore, differential expression analysis was used to select a set of biomarker genes, providing a valuable tool that can be used to monitor the cheese-making process.

  4. Longitudinal and Cross-sectional Analyses of Lung Function in Toluene Diisocyanate Production Workers.

    Science.gov (United States)

    Wang, Mei Lin; Storey, Eileen; Cassidy, Laura D; Doney, Brent; Conner, Patrick R; Collins, James J; Carson, Michael; Molenaar, Don

    2017-12-01

    The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers. One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements. The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S. Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant. We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

  5. Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression

    DEFF Research Database (Denmark)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K

    2010-01-01

    Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise ...... when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application....

  6. Optimisation of a machine learning algorithm in human locomotion using principal component and discriminant function analyses

    OpenAIRE

    Bisele, M; Bencsik, M; Lewis, MGC; Barnett, CT

    2017-01-01

    Assessment methods in human locomotion often involve the description of normalised graphical profiles and/or the extraction of discrete variables. Whilst useful, these approaches may not represent the full complexity of gait data. Multivariate statistical methods, such as Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA), have been adopted since they have the potential to overcome these data handling issues. The aim of the current study was to develop and optimise a ...

  7. Defining chaos.

    Science.gov (United States)

    Hunt, Brian R; Ott, Edward

    2015-09-01

    In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call "expansion entropy," and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

  8. Defining Quantum Control Flow

    OpenAIRE

    Ying, Mingsheng; Yu, Nengkun; Feng, Yuan

    2012-01-01

    A remarkable difference between quantum and classical programs is that the control flow of the former can be either classical or quantum. One of the key issues in the theory of quantum programming languages is defining and understanding quantum control flow. A functional language with quantum control flow was defined by Altenkirch and Grattage [\\textit{Proc. LICS'05}, pp. 249-258]. This paper extends their work, and we introduce a general quantum control structure by defining three new quantu...

  9. Item response theory analyses of the Delis-Kaplan Executive Function System card sorting subtest.

    Science.gov (United States)

    Spencer, Mercedes; Cho, Sun-Joo; Cutting, Laurie E

    2018-02-02

    In the current study, we examined the dimensionality of the 16-item Card Sorting subtest of the Delis-Kaplan Executive Functioning System assessment in a sample of 264 native English-speaking children between the ages of 9 and 15 years. We also tested for measurement invariance for these items across age and gender groups using item response theory (IRT). Results of the exploratory factor analysis indicated that a two-factor model that distinguished between verbal and perceptual items provided the best fit to the data. Although the items demonstrated measurement invariance across age groups, measurement invariance was violated for gender groups, with two items demonstrating differential item functioning for males and females. Multigroup analysis using all 16 items indicated that the items were more effective for individuals whose IRT scale scores were relatively high. A single-group explanatory IRT model using 14 non-differential item functioning items showed that for perceptual ability, females scored higher than males and that scores increased with age for both males and females; for verbal ability, the observed increase in scores across age differed for males and females. The implications of these findings are discussed.

  10. Profound differences in spontaneous long-term functional recovery after defined spinal tract lesions in the rat

    NARCIS (Netherlands)

    Hendriks, William T J; Eggers, R.; Ruitenberg, Marc J; Blits, Bas; Hamers, Frank P T; Verhaagen, J.; Boer, Gerard J

    The purpose of this study was to compare spontaneous functional recovery after different spinal motor tract lesions in the rat spinal cord using three methods of analysis, the BBB, the rope test, and the CatWalk. We transected the dorsal corticospinal tract (CSTx) or the rubrospinal tract (RSTx) or

  11. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.

    Science.gov (United States)

    Sousa, Leijiane F; Portes-Junior, José A; Nicolau, Carolina A; Bernardoni, Juliana L; Nishiyama, Milton Y; Amazonas, Diana R; Freitas-de-Sousa, Luciana A; Mourão, Rosa Hv; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

    2017-04-21

    Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA 2 s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA 2 s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not

  12. Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Agnete Kirkeby

    2012-06-01

    Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

  13. 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.

  14. Structural and functional analyses of human cerebral cortex using a surface-based atlas

    Science.gov (United States)

    Van Essen, D. C.; Drury, H. A.

    1997-01-01

    We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

  15. RESPONDING AND ANALYSING: STAGES OF TEACHING FUNCTIONAL GRAMMAR IN INDONESIAN CONTEXT

    Directory of Open Access Journals (Sweden)

    Lala Bumela

    2014-07-01

    Full Text Available Abstract: This paper offers an alternative to the teaching of a functional grammar course in Indonesian TEFL tertiary level context. An issue raised here is whether the course should directly require students to undertake textual analysis or provide them first with subjective reading experiences.  This issue is inspired by Jones and Lock¹s approach to teaching grammar in context (2011. This paper reports on a study that focused on two related phases of dealing with texts: responding and analyzing.  In the first phase, students were encouraged to take a personalised approach in responding to written English texts.  They had the freedom to decide whether the texts were meaningful for them in certain ways. Mckee (2003 and Lehtonen (2000 posit that as the sole decision maker in meaning negotiation, readers perceive the meaningfulness of texts in very diverse ways. In the second phase of the study, the students undertook an individual analysis of different text types.  This study reveals that a successful textual analysis is determined by how students make sense of the texts. The analysis of context of situation, for example, becomes meaningful to students after they demonstrate a proper position as a reader.  This, in turn, helps them in gaining insights into the structure and grammar of those texts.   Keywords: systemic functional linguistics, genre-based approach, textual analysis

  16. Functional and comparative genomics analyses of pmp22 in medaka fish

    Directory of Open Access Journals (Sweden)

    Kawarabayasi Yutaka

    2009-06-01

    Full Text Available Abstract Background Pmp22, a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase of pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A. The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV. Several CMT1A model rodents have been established by overexpressing pmp22. Thus, it is thought that pmp22 expression must be tightly regulated for correct myelin formation in mammals. Interestingly, the myelin sheath is also present in other jawed vertebrates. The purpose of this study is to analyze the evolutionary conservation of the association between pmp22 transcription level and vertebrate myelin formation, and to find the conserved non-coding sequences for pmp22 regulation by comparative genomics analyses between jawed fishes and mammals. Results A transgenic pmp22 over-expression medaka fish line was established. The transgenic fish had approximately one fifth the peripheral NCV values of controls, and aberrant myelination of transgenic fish in the peripheral nerve system (PNS was observed. We successfully confirmed that medaka fish pmp22 has the same exon-intron structure as mammals, and identified some known conserved regulatory motifs. Furthermore, we found novel conserved sequences in the first intron and 3'UTR. Conclusion Medaka fish undergo abnormalities in the PNS when pmp22 transcription increases. This result indicates that an adequate pmp22 transcription level is necessary for correct myelination of jawed vertebrates. Comparison of pmp22 orthologs between distantly related species identifies evolutionary conserved sequences that contribute to precise regulation of pmp22 expression.

  17. Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting

    DEFF Research Database (Denmark)

    Nielsen, Signe Marie Borch; Vinther-Jensen, Tua; Nielsen, Jørgen E.

    2016-01-01

    dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest......Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- A nd cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular...... and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity...

  18. Extension of $b{sub f}$-continuous functions defined on a product of $b{sub f}$-groups

    Energy Technology Data Exchange (ETDEWEB)

    Sanchis, M.

    2017-07-01

    Let X be a bf -space and let G be a bf -group. By means of the exponential mapping we characterize when a bf -continuous function on X × G with values in a topologically complete sapce Z has a bf -continuous extension to β(X) × G. As a consequence we show that the product of a pseudocompact space and a bf -group is a bf -group. This result generalizes the fact that the product of a pseudocompact space and a pseudocompact group is pseudocompact. (Author)

  19. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.

    Science.gov (United States)

    Pilorge, M; Fassier, C; Le Corronc, H; Potey, A; Bai, J; De Gois, S; Delaby, E; Assouline, B; Guinchat, V; Devillard, F; Delorme, R; Nygren, G; Råstam, M; Meier, J C; Otani, S; Cheval, H; James, V M; Topf, M; Dear, T N; Gillberg, C; Leboyer, M; Giros, B; Gautron, S; Hazan, J; Harvey, R J; Legendre, P; Betancur, C

    2016-07-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Δex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Δex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Δex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive

  20. FURTHER DEFINING SPECTRAL TYPE 'Y' AND EXPLORING THE LOW-MASS END OF THE FIELD BROWN DWARF MASS FUNCTION

    International Nuclear Information System (INIS)

    Davy Kirkpatrick, J.; Gelino, Christopher R.; Griffith, Roger L.; Marsh, Kenneth A.; Cushing, Michael C.; Mace, Gregory N.; Wright, Edward L.; McLean, Ian S.; Skrutskie, Michael F.; Eisenhardt, Peter R.; Mainzer, Amanda K.; Burgasser, Adam J.; Tinney, C. G.; Parker, Stephen; Salter, Graeme

    2012-01-01

    We present the discovery of another seven Y dwarfs from the Wide-field Infrared Survey Explorer (WISE). Using these objects, as well as the first six WISE Y dwarf discoveries from Cushing et al., we further explore the transition between spectral types T and Y. We find that the T/Y boundary roughly coincides with the spot where the J – H colors of brown dwarfs, as predicted by models, turn back to the red. Moreover, we use preliminary trigonometric parallax measurements to show that the T/Y boundary may also correspond to the point at which the absolute H (1.6 μm) and W2 (4.6 μm) magnitudes plummet. We use these discoveries and their preliminary distances to place them in the larger context of the solar neighborhood. We present a table that updates the entire stellar and substellar constituency within 8 pc of the Sun, and we show that the current census has hydrogen-burning stars outnumbering brown dwarfs by roughly a factor of six. This factor will decrease with time as more brown dwarfs are identified within this volume, but unless there is a vast reservoir of cold brown dwarfs invisible to WISE, the final space density of brown dwarfs is still expected to fall well below that of stars. We also use these new Y dwarf discoveries, along with newly discovered T dwarfs from WISE, to investigate the field substellar mass function. We find that the overall space density of late-T and early-Y dwarfs matches that from simulations describing the mass function as a power law with slope –0.5 < α < 0.0; however, a power law may provide a poor fit to the observed object counts as a function of spectral type because there are tantalizing hints that the number of brown dwarfs continues to rise from late-T to early-Y. More detailed monitoring and characterization of these Y dwarfs, along with dedicated searches aimed at identifying more examples, are certainly required.

  1. Statistical improvements in functional magnetic resonance imaging analyses produced by censoring high-motion data points.

    Science.gov (United States)

    Siegel, Joshua S; Power, Jonathan D; Dubis, Joseph W; Vogel, Alecia C; Church, Jessica A; Schlaggar, Bradley L; Petersen, Steven E

    2014-05-01

    Subject motion degrades the quality of task functional magnetic resonance imaging (fMRI) data. Here, we test two classes of methods to counteract the effects of motion in task fMRI data: (1) a variety of motion regressions and (2) motion censoring ("motion scrubbing"). In motion regression, various regressors based on realignment estimates were included as nuisance regressors in general linear model (GLM) estimation. In motion censoring, volumes in which head motion exceeded a threshold were withheld from GLM estimation. The effects of each method were explored in several task fMRI data sets and compared using indicators of data quality and signal-to-noise ratio. Motion censoring decreased variance in parameter estimates within- and across-subjects, reduced residual error in GLM estimation, and increased the magnitude of statistical effects. Motion censoring performed better than all forms of motion regression and also performed well across a variety of parameter spaces, in GLMs with assumed or unassumed response shapes. We conclude that motion censoring improves the quality of task fMRI data and can be a valuable processing step in studies involving populations with even mild amounts of head movement. Copyright © 2013 Wiley Periodicals, Inc.

  2. Functional evolution of ADAMTS genes: Evidence from analyses of phylogeny and gene organization

    Directory of Open Access Journals (Sweden)

    Van Meir Erwin G

    2005-02-01

    Full Text Available Abstract Background The ADAMTS (A Disintegrin-like and Metalloprotease with Thrombospondin motifs proteins are a family of metalloproteases with sequence similarity to the ADAM proteases, that contain the thrombospondin type 1 sequence repeat motifs (TSRs common to extracellular matrix proteins. ADAMTS proteins have recently gained attention with the discovery of their role in a variety of diseases, including tissue and blood disorders, cancer, osteoarthritis, Alzheimer's and the genetic syndromes Weill-Marchesani syndrome (ADAMTS10, thrombotic thrombocytopenic purpura (ADAMTS13, and Ehlers-Danlos syndrome type VIIC (ADAMTS2 in humans and belted white-spotting mutation in mice (ADAMTS20. Results Phylogenetic analysis and comparison of the exon/intron organization of vertebrate (Homo, Mus, Fugu, chordate (Ciona and invertebrate (Drosophila and Caenorhabditis ADAMTS homologs has elucidated the evolutionary relationships of this important gene family, which comprises 19 members in humans. Conclusions The evolutionary history of ADAMTS genes in vertebrate genomes has been marked by rampant gene duplication, including a retrotransposition that gave rise to a distinct ADAMTS subfamily (ADAMTS1, -4, -5, -8, -15 that may have distinct aggrecanase and angiogenesis functions.

  3. Functional analyses of cellulose synthase genes in flax (Linum usitatissimum) by virus-induced gene silencing.

    Science.gov (United States)

    Chantreau, Maxime; Chabbert, Brigitte; Billiard, Sylvain; Hawkins, Simon; Neutelings, Godfrey

    2015-12-01

    Flax (Linum usitatissimum) bast fibres are located in the stem cortex where they play an important role in mechanical support. They contain high amounts of cellulose and so are used for linen textiles and in the composite industry. In this study, we screened the annotated flax genome and identified 14 distinct cellulose synthase (CESA) genes using orthologous sequences previously identified. Transcriptomics of 'primary cell wall' and 'secondary cell wall' flax CESA genes showed that some were preferentially expressed in different organs and stem tissues providing clues as to their biological role(s) in planta. The development for the first time in flax of a virus-induced gene silencing (VIGS) approach was used to functionally evaluate the biological role of different CESA genes in stem tissues. Quantification of transcript accumulation showed that in many cases, silencing not only affected targeted CESA clades, but also had an impact on other CESA genes. Whatever the targeted clade, inactivation by VIGS affected plant growth. In contrast, only clade 1- and clade 6-targeted plants showed modifications in outer-stem tissue organization and secondary cell wall formation. In these plants, bast fibre number and structure were severely impacted, suggesting that the targeted genes may play an important role in the establishment of the fibre cell wall. Our results provide new fundamental information about cellulose biosynthesis in flax that should facilitate future plant improvement/engineering. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  4. Experiment and density functional theory analyses of GdTaO4 single crystal

    Science.gov (United States)

    Ding, Shoujun; Kinross, Ashlie; Wang, Xiaofei; Yang, Huajun; Zhang, Qingli; Liu, Wenpeng; Sun, Dunlu

    2018-05-01

    GdTaO4 is a type of excellent materials that can be used as scintillation, laser matrix as well as self-activated phosphor has generated significant interest. Whereas its band structure, electronic structure and optical properties are still need elucidation. To solve this intriguing problem, high-quality GdTaO4 single crystal (M-type) was grown successfully using Czochralski method. Its structure as well as optical properties was determined in experiment. Moreover, a systematic theoretical calculation based on the density function theory methods were performed on M-type and M‧-type GdTaO4 and their band structure, density of state as well as optical properties were obtained. Combine with the performed experiment results, the calculated results were proved with high reliability. Hence, the calculated results obtained in this work could provide a deep understanding of GdTaO4 material, which also useful for the further investigation on GdTaO4 material.

  5. Optimisation of a machine learning algorithm in human locomotion using principal component and discriminant function analyses.

    Science.gov (United States)

    Bisele, Maria; Bencsik, Martin; Lewis, Martin G C; Barnett, Cleveland T

    2017-01-01

    Assessment methods in human locomotion often involve the description of normalised graphical profiles and/or the extraction of discrete variables. Whilst useful, these approaches may not represent the full complexity of gait data. Multivariate statistical methods, such as Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA), have been adopted since they have the potential to overcome these data handling issues. The aim of the current study was to develop and optimise a specific machine learning algorithm for processing human locomotion data. Twenty participants ran at a self-selected speed across a 15m runway in barefoot and shod conditions. Ground reaction forces (BW) and kinematics were measured at 1000 Hz and 100 Hz, respectively from which joint angles (°), joint moments (N.m.kg-1) and joint powers (W.kg-1) for the hip, knee and ankle joints were calculated in all three anatomical planes. Using PCA and DFA, power spectra of the kinematic and kinetic variables were used as a training database for the development of a machine learning algorithm. All possible combinations of 10 out of 20 participants were explored to find the iteration of individuals that would optimise the machine learning algorithm. The results showed that the algorithm was able to successfully predict whether a participant ran shod or barefoot in 93.5% of cases. To the authors' knowledge, this is the first study to optimise the development of a machine learning algorithm.

  6. The Research Search For The Least Beneficial Overcast Sky And Progress In Defining Its Luminance Gradation Function

    Directory of Open Access Journals (Sweden)

    Kittler R.

    2014-09-01

    Full Text Available Recently illuminance levels under ISO/CIE homogeneous standard sky types were characterised in their relative terms after ISO/CIE (2004, 2003 standardised as normalised by the luminance in the zenith. Sky luminance and horizontal illuminance based on the gradation and scattering indicatrix functions, including the extreme overcast cases frequently encountered in nature, were recently determined in absolute physical units of luminance in kilocandles per meter square and of illuminance in kilolux. The historical search to find energy and visibility critical sky luminance distributions shows a progression of steps in studying the worst or critical overcast situations. That progression has enabled the determination and evaluation of interior illuminance for comparison of the merits of dual daylighting and artificial lighting under established criteria for comfortable visibility.

  7. Defining the contributions of permanent electrostatics, Pauli repulsion, and dispersion in density functional theory calculations of intermolecular interaction energies

    Energy Technology Data Exchange (ETDEWEB)

    Horn, Paul R., E-mail: prhorn@berkeley.edu; Mao, Yuezhi; Head-Gordon, Martin, E-mail: mhg@cchem.berkeley.edu [Kenneth S. Pitzer Center for Theoretical Chemistry, Department of Chemistry, University of California, Berkeley, California 94720, USA and Chemical Sciences Division Lawrence Berkeley National Laboratory Berkeley, California 94720 (United States)

    2016-03-21

    In energy decomposition analysis of Kohn-Sham density functional theory calculations, the so-called frozen (or pre-polarization) interaction energy contains contributions from permanent electrostatics, dispersion, and Pauli repulsion. The standard classical approach to separate them suffers from several well-known limitations. We introduce an alternative scheme that employs valid antisymmetric electronic wavefunctions throughout and is based on the identification of individual fragment contributions to the initial supersystem wavefunction as determined by an energetic optimality criterion. The density deformations identified with individual fragments upon formation of the initial supersystem wavefunction are analyzed along with the distance dependence of the new and classical terms for test cases that include the neon dimer, ammonia borane, water-Na{sup +}, water-Cl{sup −}, and the naphthalene dimer.

  8. Association between MRI-defined osteoarthritis, pain, function and strength 3-10 years following knee joint injury in youth sport.

    Science.gov (United States)

    Whittaker, Jackie L; Toomey, Clodagh M; Woodhouse, Linda J; Jaremko, Jacob L; Nettel-Aguirre, Alberto; Emery, Carolyn A

    2017-10-10

    Youth and young adults who participate in sport have an increased risk of knee injury and subsequent osteoarthritis. Improved understanding of the relationship between structural and clinical outcomes postinjury could inform targeted osteoarthritis prevention interventions. This secondary analysis examines the association between MRI-defined osteoarthritis and self-reported and functional outcomes, 3-10 years following youth sport-related knee injury in comparison to healthy controls. Participants included a subsample (n=146) of the Alberta Youth Prevention of Early Osteoarthritis cohort: specifically, 73 individuals with 3-10 years history of sport-related intra-articular knee injury and 73 age-matched, sex-matched and sport-matched controls with completed MRI studies. Outcomes included: MRI-defined osteoarthritis, radiographic osteoarthritis, Knee Injury and Osteoarthritis Outcome Score, Intermittent and Constant Osteoarthritis Pain, knee extensor/flexor strength, triple-hop and Y-balance test. Descriptive statistics and univariate logistic regression were used to compare those with and without MRI-defined osteoarthritis. Associations between MRI-defined osteoarthritis and each outcome were assessed using multivariable linear regression considering the influence of injury history, sex, body mass index and time since injury. Participant median age was 23 years (range 15-27), and 63% were female. MRI-defined osteoarthritis varied by injury history, injury type and surgical history and was not isolated to participants with ACL and/or meniscal injuries. Those with a previous knee injury had 10-fold (95% CI 2.3 to 42.8) greater odds of MRI-defined osteoarthritis than uninjured participants. MRI-defined osteoarthritis was independently significantly associated with quality of life, but not symptoms, strength or function. MRI-detected structural changes 3-10 years following youth sport-related knee injury may not dictate clinical symptomatology, strength or function

  9. Model tests and numerical analyses on horizontal impedance functions of inclined single piles embedded in cohesionless soil

    Science.gov (United States)

    Goit, Chandra Shekhar; Saitoh, Masato

    2013-03-01

    Horizontal impedance functions of inclined single piles are measured experimentally for model soil-pile systems with both the effects of local soil nonlinearity and resonant characteristics. Two practical pile inclinations of 5° and 10° in addition to a vertical pile embedded in cohesionless soil and subjected to lateral harmonic pile head loadings for a wide range of frequencies are considered. Results obtained with low-to-high amplitude of lateral loadings on model soil-pile systems encased in a laminar shear box show that the local nonlinearities have a profound impact on the horizontal impedance functions of piles. Horizontal impedance functions of inclined piles are found to be smaller than the vertical pile and the values decrease as the angle of pile inclination increases. Distinct values of horizontal impedance functions are obtained for the `positive' and `negative' cycles of harmonic loadings, leading to asymmetric force-displacement relationships for the inclined piles. Validation of these experimental results is carried out through three-dimensional nonlinear finite element analyses, and the results from the numerical models are in good agreement with the experimental data. Sensitivity analyses conducted on the numerical models suggest that the consideration of local nonlinearity at the vicinity of the soil-pile interface influence the response of the soil-pile systems.

  10. Phylogeny, Functional Annotation, and Protein Interaction Network Analyses of the Xenopus tropicalis Basic Helix-Loop-Helix Transcription Factors

    Directory of Open Access Journals (Sweden)

    Wuyi Liu

    2013-01-01

    Full Text Available The previous survey identified 70 basic helix-loop-helix (bHLH proteins, but it was proved to be incomplete, and the functional information and regulatory networks of frog bHLH transcription factors were not fully known. Therefore, we conducted an updated genome-wide survey in the Xenopus tropicalis genome project databases and identified 105 bHLH sequences. Among the retrieved 105 sequences, phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding supergroups. Next, gene ontology (GO enrichment analyses showed 65 significant GO annotations of biological processes and molecular functions and KEGG pathways counted in frequency. To explore the functional pathways, regulatory gene networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins, the identified bHLH genes were put into the databases KOBAS and STRING to get the signaling information of pathways and protein interaction networks according to available public databases and known protein interactions. From the genome annotation and pathway analysis using KOBAS, we identified 16 pathways in the Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins were identified, and many hub proteins created a tight network or a functional module within the protein families.

  11. Working memory circuit as a function of increasing age in healthy adolescence: A systematic review and meta-analyses.

    Science.gov (United States)

    Andre, Julia; Picchioni, Marco; Zhang, Ruibin; Toulopoulou, Timothea

    2016-01-01

    Working memory ability matures through puberty and early adulthood. Deficits in working memory are linked to the risk of onset of neurodevelopmental disorders such as schizophrenia, and there is a significant temporal overlap between the peak of first episode psychosis risk and working memory maturation. In order to characterize the normal working memory functional maturation process through this critical phase of cognitive development we conducted a systematic review and coordinate based meta-analyses of all the available primary functional magnetic resonance imaging studies (n = 382) that mapped WM function in healthy adolescents (10-17 years) and young adults (18-30 years). Activation Likelihood Estimation analyses across all WM tasks revealed increased activation with increasing subject age in the middle frontal gyrus (BA6) bilaterally, the left middle frontal gyrus (BA10), the left precuneus and left inferior parietal gyri (BA7; 40). Decreased activation with increasing age was found in the right superior frontal (BA8), left junction of postcentral and inferior parietal (BA3/40), and left limbic cingulate gyrus (BA31). These results suggest that brain activation during adolescence increased with age principally in higher order cortices, part of the core working memory network, while reductions were detected in more diffuse and potentially more immature neural networks. Understanding the process by which the brain and its cognitive functions mature through healthy adulthood may provide us with new clues to understanding the vulnerability to neurodevelopmental disorders.

  12. Working memory circuit as a function of increasing age in healthy adolescence: A systematic review and meta-analyses

    Directory of Open Access Journals (Sweden)

    Julia Andre

    2016-01-01

    Full Text Available Working memory ability matures through puberty and early adulthood. Deficits in working memory are linked to the risk of onset of neurodevelopmental disorders such as schizophrenia, and there is a significant temporal overlap between the peak of first episode psychosis risk and working memory maturation. In order to characterize the normal working memory functional maturation process through this critical phase of cognitive development we conducted a systematic review and coordinate based meta-analyses of all the available primary functional magnetic resonance imaging studies (n = 382 that mapped WM function in healthy adolescents (10–17 years and young adults (18–30 years. Activation Likelihood Estimation analyses across all WM tasks revealed increased activation with increasing subject age in the middle frontal gyrus (BA6 bilaterally, the left middle frontal gyrus (BA10, the left precuneus and left inferior parietal gyri (BA7; 40. Decreased activation with increasing age was found in the right superior frontal (BA8, left junction of postcentral and inferior parietal (BA3/40, and left limbic cingulate gyrus (BA31. These results suggest that brain activation during adolescence increased with age principally in higher order cortices, part of the core working memory network, while reductions were detected in more diffuse and potentially more immature neural networks. Understanding the process by which the brain and its cognitive functions mature through healthy adulthood may provide us with new clues to understanding the vulnerability to neurodevelopmental disorders.

  13. Functional analyses of the three simian hemorrhagic fever virus nonstructural protein 1 papain-like proteases.

    Science.gov (United States)

    Vatter, Heather A; Di, Han; Donaldson, Eric F; Radu, Gertrud U; Maines, Taronna R; Brinton, Margo A

    2014-08-01

    The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in in vitro transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the in vitro reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins. SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of in vitro autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites

  14. Establishment of mitochondrial pyruvate carrier 1 (MPC1) gene knockout mice with preliminary gene function analyses

    Science.gov (United States)

    Li, Xiaoli; Li, Yaqing; Han, Gaoyang; Li, Xiaoran; Ji, Yasai; Fan, Zhirui; Zhong, Yali; Cao, Jing; Zhao, Jing; Mariusz, Goscinski; Zhang, Mingzhi; Wen, Jianguo; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Pyruvate plays a critical role in the mitochondrial tricarboxylic acid (TCA) cycle, and it is the center product for the synthesis of amino acids, carbohydrates and fatty acids. Pyruvate transported across the inner mitochondrial membrane appears to be essential in anabolic and catabolic intermediary metabolism. The mitochondrial pyruvate carrier (MPC) mounted in the inner membrane of mitochondria serves as the channel to facilitate pyruvate permeating. In mammals, the MPC is formed by two paralogous subunits, MPC1 and MPC2. It is known that complete ablation of MPC2 in mice causes death on the 11th or 12th day of the embryonic period. However, MPC1 deletion and the knowledge of gene function in vivo are lacking. Using the new technology of gene manipulation known as Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 (CRISPR/Cas9) systems, we gained stable MPC1 gene heterozygous mutation mice models, and the heterozygous mutations could be stably maintained in their offsprings. Only one line with homozygous 27 bases deletion in the first exon was established, but no offsprings could be obtained after four months of mating experiments, indicating infertility of the mice with such homozygous deletion. The other line of MPC1 knockout (KO) mice was only heterozygous, which mutated in the first exon with a terminator shortly afterwards. These two lines of MPC1 KO mice showed lower fertility and significantly higher bodyweight in the females. We concluded that heterozygous MPC1 KO weakens fertility and influences the metabolism of glucose and fatty acid and bodyweight in mice. PMID:27835892

  15. Molecular cloning, functional identification and expressional analyses of FasL in Tilapia, Oreochromis niloticus.

    Science.gov (United States)

    Ma, Tai-yang; Wu, Jin-ying; Gao, Xiao-ke; Wang, Jing-yuan; Zhan, Xu-liang; Li, Wen-sheng

    2014-10-01

    FasL is the most extensively studied apoptosis ligand. In 2000, tilapia FasL was identified using anti-human FasL monoclonal antibody by Evans's research group. Recently, a tilapia FasL-like protein of smaller molecule weight was predicted in Genbank (XM_003445156.2). Based on several clues drawn from previous studies, we cast doubt on the authenticity of the formerly identified tilapia FasL. Conversely, using reverse transcription polymerase chain reaction (RT-PCR), the existence of the predicted FasL-like was verified at the mRNA level (The Genbank accession number of the FasL mRNA sequence we cloned is KM008610). Through multiple alignments, this FasL-like protein was found to be highly similar to the FasL of the Japanese flounder. Moreover, we artificially expressed the functional region of the predicted protein and later confirmed its apoptosis-inducing activity using a methyl thiazolyl tetrazolium (MTT) assay, Annexin-V/Propidium iodide (PI) double staining, and DNA fragment detection. Supported by these evidences, we suggest that the predicted protein is the authentic tilapia FasL. To advance this research further, tilapia FasL mRNA and its protein across different tissues were quantified. High expression levels were identified in the tilapia immune system and sites where active cell turnover conservatively occurs. In this regard, FasL may assume an active role in the immune system and cell homeostasis maintenance in tilapia, similar to that shown in other species. In addition, because the distribution pattern of FasL mRNA did not synchronize with that of the protein, post-transcriptional expression regulation is suggested. Such regulation may be dominated by potential adenylate- and uridylate-rich elements (AREs) featuring AUUUA repeats found in the 3' untranslated region (UTR) of tilapia FasL mRNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies

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    Sanem Eren Akarcan

    2017-01-01

    Full Text Available Chronic Mucocutaneous Candidiasis (CMC is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF (c.1154 C>T, p.Thr385Met in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

  17. Co-ordinated functions of Mms proteins define the surface structure of cubo-octahedral magnetite crystals in magnetotactic bacteria.

    Science.gov (United States)

    Arakaki, Atsushi; Yamagishi, Ayana; Fukuyo, Ayumi; Tanaka, Masayoshi; Matsunaga, Tadashi

    2014-08-01

    Magnetotactic bacteria synthesize magnetosomes comprised of membrane-enveloped single crystalline magnetite (Fe3 O4 ). The size and morphology of the nano-sized magnetite crystals (Mms (Mms5, Mms6, Mms7, and Mms13), was previously isolated from the surface of cubo-octahedral magnetite crystals in Magnetospirillum magneticum strain AMB-1. Analysis of an mms6 gene deletion mutant suggested that the Mms6 protein plays a major role in the regulation of magnetite crystal size and morphology. In this study, we constructed various mms gene deletion mutants and characterized the magnetite crystals formed by the mutant strains. Comparative analysis showed that all mms genes were involved in the promotion of crystal growth in different manners. The phenotypic characterization of magnetites also suggested that these proteins are involved in controlling the geometries of the crystal surface structures. Thus, the co-ordinated functions of Mms proteins regulate the morphology of the cubo-octahedral magnetite crystals in magnetotactic bacteria. © 2014 John Wiley & Sons Ltd.

  18. Optimization of soaking stage in technological process of wheat germination by hydroponic method when objective function is defined implicitly

    Science.gov (United States)

    Koneva, M. S.; Rudenko, O. V.; Usatikov, S. V.; Bugayets, N. A.; Tamova, M. Yu; Fedorova, M. A.

    2018-05-01

    The increase in the efficiency of the "numerical" technology for solving computational problems of parametric optimization of the technological process of hydroponic germination of wheat grains is considered. In this situation, the quality criteria are contradictory and a part of them is given by implicit functions of many variables. One of the main stages, soaking, determining the time and quality of germinated wheat grain is studied, when grain receives the required amount of moisture and air oxygen for germination and subsequently accumulates enzymes. A solution algorithm for this problem is suggested implemented by means of software packages Statistica v.10 and MathCAD v.15. The use of the proposed mathematical models describing the processes of hydroponic soaking of spring soft wheat varieties made it possible to determine optimal conditions of germination. The results of investigations show that the type of aquatic environment used for soaking has a great influence on the process of water absorption, especially the chemical composition of the germinated material. The use of the anolyte of electrochemically activated water (ECHA-water) intensifies the process from 5.83 to 4 hours for wheat variety «Altayskaya 105» and from 13 to 8.8 hours - for «Pobla Runo».

  19. Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

    Science.gov (United States)

    Feder, Stephan; Sundermann, Benedikt; Wersching, Heike; Teuber, Anja; Kugel, Harald; Teismann, Henning; Heindel, Walter; Berger, Klaus; Pfleiderer, Bettina

    2017-11-01

    Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Proteomic and Functional Analyses of the Virion Transmembrane Proteome of Cyprinid Herpesvirus 3.

    Science.gov (United States)

    Vancsok, Catherine; Peñaranda, M Michelle D; Raj, V Stalin; Leroy, Baptiste; Jazowiecka-Rakus, Joanna; Boutier, Maxime; Gao, Yuan; Wilkie, Gavin S; Suárez, Nicolás M; Wattiez, Ruddy; Gillet, Laurent; Davison, Andrew J; Vanderplasschen, Alain F C

    2017-11-01

    Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to CyHV-3 VTPs. Using mass spectrometry approaches, we identified 16 VTPs of the CyHV-3 FL strain. Mutagenesis experiments demonstrated that eight of these proteins are essential for viral growth in vitro (open reading frame 32 [ORF32], ORF59, ORF81, ORF83, ORF99, ORF106, ORF115, and ORF131), and eight are nonessential (ORF25, ORF64, ORF65, ORF108, ORF132, ORF136, ORF148, and ORF149). Among the nonessential proteins, deletion of ORF25, ORF132, ORF136, ORF148, or ORF149 affects viral replication in vitro , and deletion of ORF25, ORF64, ORF108, ORF132, or ORF149 impacts plaque size. Lack of ORF148 or ORF25 causes attenuation in vivo to a minor or major extent, respectively. The safety and efficacy of a virus lacking ORF25 were compared to those of a previously described vaccine candidate deleted for ORF56 and ORF57 (Δ56-57). Using quantitative PCR, we demonstrated that the ORF25 deleted virus infects fish through skin infection and then spreads to internal organs as reported previously for the wild-type parental virus and the Δ56-57 virus. However, compared to the parental wild-type virus, the replication of the ORF25-deleted virus was reduced in intensity and duration to levels similar to those observed for the Δ56-57 virus. Vaccination of fish with a virus lacking ORF25 was safe but had low efficacy at the doses tested. This characterization of the virion transmembrane proteome of CyHV-3 provides a firm basis for further research on alloherpesvirus VTPs. IMPORTANCE Virion transmembrane proteins play key roles in the biology of herpesviruses. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and the causative agent of major economic losses in common and koi carp worldwide. In this study of the virion transmembrane proteome of CyHV-3, the

  1. Defining the functional domain of programmed cell death 10 through its interactions with phosphatidylinositol-3,4,5-trisphosphate.

    Directory of Open Access Journals (Sweden)

    Christopher F Dibble

    2010-07-01

    Full Text Available Cerebral cavernous malformations (CCM are vascular abnormalities of the central nervous system predisposing blood vessels to leakage, leading to hemorrhagic stroke. Three genes, Krit1 (CCM1, OSM (CCM2, and PDCD10 (CCM3 are involved in CCM development. PDCD10 binds specifically to PtdIns(3,4,5P3 and OSM. Using threading analysis and multi-template modeling, we constructed a three-dimensional model of PDCD10. PDCD10 appears to be a six-helical-bundle protein formed by two heptad-repeat-hairpin structures (alpha1-3 and alpha4-6 sharing the closest 3D homology with the bacterial phosphate transporter, PhoU. We identified a stretch of five lysines forming an amphipathic helix, a potential PtdIns(3,4,5P3 binding site, in the alpha5 helix. We generated a recombinant wild-type (WT and three PDCD10 mutants that have two (Delta2KA, three (Delta3KA, and five (Delta5KA K to A mutations. Delta2KA and Delta3KA mutants hypothetically lack binding residues to PtdIns(3,4,5P3 at the beginning and the end of predicted helix, while Delta5KA completely lacks all predicted binding residues. The WT, Delta2KA, and Delta3KA mutants maintain their binding to PtdIns(3,4,5P3. Only the Delta5KA abolishes binding to PtdIns(3,4,5P3. Both Delta5KA and WT show similar secondary and tertiary structures; however, Delta5KA does not bind to OSM. When WT and Delta5KA are co-expressed with membrane-bound constitutively-active PI3 kinase (p110-CAAX, the majority of the WT is co-localized with p110-CAAX at the plasma membrane where PtdIns(3,4,5P3 is presumably abundant. In contrast, the Delta5KA remains in the cytoplasm and is not present in the plasma membrane. Combining computational modeling and biological data, we propose that the CCM protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5P3.

  2. A New Triangular Hybrid Displacement Function Element for Static and Free Vibration Analyses of Mindlin-Reissner Plate

    Directory of Open Access Journals (Sweden)

    Jun-Bin Huang

    Full Text Available Abstract A new 3-node triangular hybrid displacement function Mindlin-Reissner plate element is developed. Firstly, the modified variational functional of complementary energy for Mindlin-Reissner plate, which is eventually expressed by a so-called displacement function F, is proposed. Secondly, the locking-free formulae of Timoshenko’s beam theory are chosen as the deflection, rotation, and shear strain along each element boundary. Thirdly, seven fundamental analytical solutions of the displacement function F are selected as the trial functions for the assumed resultant fields, so that the assumed resultant fields satisfy all governing equations in advance. Finally, the element stiffness matrix of the new element, denoted by HDF-P3-7β, is derived from the modified principle of complementary energy. Together with the diagonal inertia matrix of the 3-node triangular isoparametric element, the proposed element is also successfully generalized to the free vibration problems. Numerical results show that the proposed element exhibits overall remarkable performance in all benchmark problems, especially in the free vibration analyses.

  3. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  4. Validity of premature ejaculation diagnostic tool and its association with International Index of Erectile Function-15 in Chinese men with evidence-based-defined premature ejaculation

    Directory of Open Access Journals (Sweden)

    Dong-Dong Tang

    2018-01-01

    Full Text Available The premature ejaculation diagnostic tool (PEDT is a brief diagnostic measure to assess premature ejaculation (PE. However, there is insufficient evidence regarding its validity in the new evidence-based-defined PE. This study was performed to evaluate the validity of PEDT and its association with IIEF-15 in different types of evidence-based-defined PE. From June 2015 to January 2016, a total of 260 men complaining of PE and defined as lifelong PE (LPE/acquired PE (APE according to the evidence-based definition from Andrology Clinic of the First Affiliated Hospital of Anhui Medical University, along with 104 male healthy controls without PE from a medical examination center, were enrolled in this study. All individuals completed questionnaires including demographics, medical and sexual history, as well as PEDT and IIEF-15. After statistical analysis, it was found that men with PE reported higher PEDT scores (14.28 ± 3.05 and lower IIEF-15 (41.26 ± 8.20 than men without PE (PEDT: 5.32 ± 3.42, IIEF-15: 52.66 ± 6.86, P < 0.001 for both. It was suggested that a score of ≥9 indicated PE in both LPE and APE by sensitivity and specificity analyses (sensitivity: 0.875, 0.913; specificity: 0.865, 0.865, respectively. In addition, IIEF-15 were higher in men with LPE (42.64 ± 8.11 than APE (39.43 ± 7.84, P < 0.001. After adjusting for age, IIEF-15 was negatively related to PEDT in men with LPE (adjust r = −0.225, P < 0.001 and APE (adjust r = −0.378, P < 0.001. In this study, we concluded that PEDT was valid in the diagnosis of evidenced-based-defined PE. Furthermore, IIEF-15 was negatively related to PEDT in men with different types of PE.

  5. A Rapid and Efficient Method for Purifying High Quality Total RNA from Peaches (Prunus persica for Functional Genomics Analyses

    Directory of Open Access Journals (Sweden)

    LEE MEISEL

    2005-01-01

    Full Text Available Prunus persica has been proposed as a genomic model for deciduous trees and the Rosaceae family. Optimized protocols for RNA isolation are necessary to further advance studies in this model species such that functional genomics analyses may be performed. Here we present an optimized protocol to rapidly and efficiently purify high quality total RNA from peach fruits (Prunus persica. Isolating high-quality RNA from fruit tissue is often difficult due to large quantities of polysaccharides and polyphenolic compounds that accumulate in this tissue and co-purify with the RNA. Here we demonstrate that a modified version of the method used to isolate RNA from pine trees and the woody plant Cinnamomun tenuipilum is ideal for isolating high quality RNA from the fruits of Prunus persica. This RNA may be used for many functional genomic based experiments such as RT-PCR and the construction of large-insert cDNA libraries.

  6. Meta-analyses of cognitive and motor function in youth aged 16 years and younger who subsequently develop schizophrenia.

    Science.gov (United States)

    Dickson, H; Laurens, K R; Cullen, A E; Hodgins, S

    2012-04-01

    Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not. Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement. Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13. These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.

  7. Cross-cultural and sex differences in the Emotional Skills and Competence Questionnaire scales: Challenges of differential item functioning analyses

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    Bo Molander

    2009-11-01

    Full Text Available University students in Croatia, Slovenia, and Sweden (N = 1129 were examined by means of the Emotional Skills and Competence Questionnaire (Takšić, 1998. Results showed a significant effect for the sex factor only on the total-score scale, women scoring higher than men, but significant effects were obtained for country, as well as for sex, on the Express and Label (EL and Perceive and Understand (PU subscales. Sweden showed higher scores than Croatia and Slovenia on the EL scale, and Slovenia showed higher scores than Croatia and Sweden on the PU scale. In subsequent analyses of differential item functioning (DIF, comparisons were carried out for pairs of countries. The analyses revealed that a large proportion of the items in the total-score scale were potentially biased, most so for the Croatian-Swedish comparison, less for the Slovenian-Swedish comparison, and least for the Croatian-Slovenian comparison. These findings give doubts about the validity of mean score differences in comparisons of countries. However, DIF analyses of sex differences within each country show very few DIF items, indicating that the ESCQ instrument works well within each cultural/linguistic setting. Possible explanations of the findings are discussed, and improvements for future studies are suggested.

  8. Item response theory analysis of the life orientation test-revised: age and gender differential item functioning analyses.

    Science.gov (United States)

    Steca, Patrizia; Monzani, Dario; Greco, Andrea; Chiesi, Francesca; Primi, Caterina

    2015-06-01

    This study is aimed at testing the measurement properties of the Life Orientation Test-Revised (LOT-R) for the assessment of dispositional optimism by employing item response theory (IRT) analyses. The LOT-R was administered to a large sample of 2,862 Italian adults. First, confirmatory factor analyses demonstrated the theoretical conceptualization of the construct measured by the LOT-R as a single bipolar dimension. Subsequently, IRT analyses for polytomous, ordered response category data were applied to investigate the items' properties. The equivalence of the items across gender and age was assessed by analyzing differential item functioning. Discrimination and severity parameters indicated that all items were able to distinguish people with different levels of optimism and adequately covered the spectrum of the latent trait. Additionally, the LOT-R appears to be gender invariant and, with minor exceptions, age invariant. Results provided evidence that the LOT-R is a reliable and valid measure of dispositional optimism. © The Author(s) 2014.

  9. An impedance function approach for soil-structure interaction analyses including structure-to-structure interaction effects

    International Nuclear Information System (INIS)

    Gantayat, A.; Kamil, H.

    1981-01-01

    The dynamic soil-structure and structure-to-structure interaction effects may be determined in one of the two ways: by modeling the entire soil-structure system by a finite-element model, or by using a frequency-dependent (or frequency-independent) impedance function approach. In seismic design of nuclear power plant structures, the normal practice is to use the first approach because of its simplicity and easy availability of computer codes to perform such analyses. However, in the finite-element approach, because of the size and cost restrictions, the three-dimensional behavior of the entire soil-structure system and the radiation damping in soil are only approximately included by using a two-dimensional finite-element mesh. In using the impedance function approach, the soil-structure analyses can be performed in four steps: (a) determination of the dynamic properties of the fixed base superstructure, (b) determination of foundation and structure impedance matrices and input motions, (c) evaluation of foundation motion, (d) analysis of the fixed base superstructure using computed foundation motion. (orig./RW)

  10. Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

    Science.gov (United States)

    Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

    2017-08-21

    Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

  11. Defining Platelet Function During Polytrauma

    Science.gov (United States)

    2014-04-01

    scaffold of the clot after its thrombin-induced polymerization to fibrin fibers. Formation of a stiff fibrin fiber network and its contraction by platelet...In another study (PROTEC T) Refused Participat ion (Yes=Y, No=N, W=Unqua lified , Refused further draws (agreed to keep previous data

  12. Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model

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    Alvaro Plaza Reyes

    2016-01-01

    Full Text Available Human embryonic stem cell (hESC-derived retinal pigment epithelial (RPE cells could replace lost tissue in geographic atrophy (GA but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model.

  13. Characterization of Aeromonas hydrophila Wound Pathotypes by Comparative Genomic and Functional Analyses of Virulence Genes

    Science.gov (United States)

    Grim, Christopher J.; Kozlova, Elena V.; Sha, Jian; Fitts, Eric C.; van Lier, Christina J.; Kirtley, Michelle L.; Joseph, Sandeep J.; Read, Timothy D.; Burd, Eileen M.; Tall, Ben D.; Joseph, Sam W.; Horneman, Amy J.; Chopra, Ashok K.; Shak, Joshua R.

    2013-01-01

    ABSTRACT Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966T, and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966T. The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966T and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. PMID:23611906

  14. Evaluation of jaw and neck muscle activities while chewing using EMG-EMG transfer function and EMG-EMG coherence function analyses in healthy subjects.

    Science.gov (United States)

    Ishii, Tomohiro; Narita, Noriyuki; Endo, Hiroshi

    2016-06-01

    This study aims to quantitatively clarify the physiological features in rhythmically coordinated jaw and neck muscle EMG activities while chewing gum using EMG-EMG transfer function and EMG-EMG coherence function analyses in 20 healthy subjects. The chewing side masseter muscle EMG signal was used as the reference signal, while the other jaw (non-chewing side masseter muscle, bilateral anterior temporal muscles, and bilateral anterior digastric muscles) and neck muscle (bilateral sternocleidomastoid muscles) EMG signals were used as the examined signals in EMG-EMG transfer function and EMG-EMG coherence function analyses. Chewing-related jaw and neck muscle activities were aggregated in the first peak of the power spectrum in rhythmic chewing. The gain in the peak frequency represented the power relationships between jaw and neck muscle activities during rhythmic chewing. The phase in the peak frequency represented the temporal relationships between the jaw and neck muscle activities, while the non-chewing side neck muscle presented a broad range of distributions across jaw closing and opening phases. Coherence in the peak frequency represented the synergistic features in bilateral jaw closing muscles and chewing side neck muscle activities. The coherence and phase in non-chewing side neck muscle activities exhibited a significant negative correlation. From above, the bilateral coordination between the jaw and neck muscle activities is estimated while chewing when the non-chewing side neck muscle is synchronously activated with the jaw closing muscles, while the unilateral coordination is estimated when the non-chewing side neck muscle is irregularly activated in the jaw opening phase. Thus, the occurrence of bilateral or unilateral coordinated features in the jaw and neck muscle activities may correspond to the phase characteristics in the non-chewing side neck muscle activities during rhythmical chewing. Considering these novel findings in healthy subjects, EMG

  15. Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

    Science.gov (United States)

    Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

    2017-07-07

    Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

  16. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

    Directory of Open Access Journals (Sweden)

    Wenbo Tang

    Full Text Available Genome-wide association studies (GWAS have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1 in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7. In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8 at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  17. Metagenomic and functional analyses of the consequences of reduction of bacterial diversity on soil functions and bioremediation in diesel-contaminated microcosms.

    Science.gov (United States)

    Jung, Jaejoon; Philippot, Laurent; Park, Woojun

    2016-03-14

    The relationship between microbial biodiversity and soil function is an important issue in ecology, yet most studies have been performed in pristine ecosystems. Here, we assess the role of microbial diversity in ecological function and remediation strategies in diesel-contaminated soils. Soil microbial diversity was manipulated using a removal by dilution approach and microbial functions were determined using both metagenomic analyses and enzymatic assays. A shift from Proteobacteria- to Actinobacteria-dominant communities was observed when species diversity was reduced. Metagenomic analysis showed that a large proportion of functional gene categories were significantly altered by the reduction in biodiversity. The abundance of genes related to the nitrogen cycle was significantly reduced in the low-diversity community, impairing denitrification. In contrast, the efficiency of diesel biodegradation was increased in the low-diversity community and was further enhanced by addition of red clay as a stimulating agent. Our results suggest that the relationship between microbial diversity and ecological function involves trade-offs among ecological processes, and should not be generalized as a positive, neutral, or negative relationship.

  18. Performance evaluation of multi-stratum resources integration based on network function virtualization in software defined elastic data center optical interconnect.

    Science.gov (United States)

    Yang, Hui; Zhang, Jie; Ji, Yuefeng; Tian, Rui; Han, Jianrui; Lee, Young

    2015-11-30

    Data center interconnect with elastic optical network is a promising scenario to meet the high burstiness and high-bandwidth requirements of data center services. In our previous work, we implemented multi-stratum resilience between IP and elastic optical networks that allows to accommodate data center services. In view of this, this study extends to consider the resource integration by breaking the limit of network device, which can enhance the resource utilization. We propose a novel multi-stratum resources integration (MSRI) architecture based on network function virtualization in software defined elastic data center optical interconnect. A resource integrated mapping (RIM) scheme for MSRI is introduced in the proposed architecture. The MSRI can accommodate the data center services with resources integration when the single function or resource is relatively scarce to provision the services, and enhance globally integrated optimization of optical network and application resources. The overall feasibility and efficiency of the proposed architecture are experimentally verified on the control plane of OpenFlow-based enhanced software defined networking (eSDN) testbed. The performance of RIM scheme under heavy traffic load scenario is also quantitatively evaluated based on MSRI architecture in terms of path blocking probability, provisioning latency and resource utilization, compared with other provisioning schemes.

  19. Food web functioning of the benthopelagic community in a deep-sea seamount based on diet and stable isotope analyses

    Science.gov (United States)

    Preciado, Izaskun; Cartes, Joan E.; Punzón, Antonio; Frutos, Inmaculada; López-López, Lucía; Serrano, Alberto

    2017-03-01

    Trophic interactions in the deep-sea fish community of the Galicia Bank seamount (NE Atlantic) were inferred by using stomach contents analyses (SCA) and stable isotope analyses (SIA) of 27 fish species and their main prey items. Samples were collected during three surveys performed in 2009, 2010 and 2011 between 625 and 1800 m depth. Three main trophic guilds were determined using SCA data: pelagic, benthopelagic and benthic feeders, respectively. Vertically migrating macrozooplankton and meso-bathypelagic shrimps were identified to play a key role as pelagic prey for the deep sea fish community of the Galicia Bank. Habitat overlap was hardly detected; as a matter of fact, when species coexisted most of them evidenced a low dietary overlap, indicating a high degree of resource partitioning. A high potential competition, however, was observed among benthopelagic feeders, i.e.: Etmopterus spinax, Hoplostethus mediterraneus and Epigonus telescopus. A significant correlation was found between δ15N and δ13C for all the analysed species. When calculating Trophic Levels (TLs) for the main fish species, using both the SCA and SIA approaches, some discrepancies arose: TLs calculated from SIA were significantly higher than those obtained from SCA, probably indicating a higher consumption of benthic-suprabenthic prey in the previous months. During the summer, food web functioning in the Galicia Bank was more influenced by the assemblages dwelling in the water column than by deep-sea benthos, which was rather scarce in the summer samples. These discrepancies demonstrate the importance of using both approaches, SCA (snapshot of diet) and SIA (assimilated food in previous months), when attempting trophic studies, if an overview of food web dynamics in different compartments of the ecosystem is to be obtained.

  20. Size-dependent electro-magneto-elastic bending analyses of the shear-deformable axisymmetric functionally graded circular nanoplates

    Science.gov (United States)

    Arefi, Mohammad; Zenkour, Ashraf M.

    2017-10-01

    This paper develops nonlocal elasticity equations and magneto-electro-elastic relations to size-dependent electro-magneto-elastic bending analyses of the functionally graded axisymmetric circular nanoplates based on the first-order shear deformation theory. All material properties are graded along the thickness direction based on exponential varying. It is assumed that a circular nanoplate is made from piezo-magnetic materials. The energy method and Ritz approach is employed for the derivation of governing equations of electro-magneto-elastic bending and the solution of the problem, respectively. The nanoplate is subjected to applied electric and magnetic potentials at top and transverse loads while it is rested on Pasternak's foundation. Some important numerical results are presented in various figures to show the influence of applied electric and magnetic potentials, small scale parameter and inhomogeneous index of an exponentially graded nanoplate.

  1. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules, F9-F11

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with three of the functional modules in the code. Those are the Morse-SGC for the SCALE system, Heating 7.2, and KENO V.a. The manual describes the latest released versions of the codes.

  2. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules, F9-F11

    International Nuclear Information System (INIS)

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with three of the functional modules in the code. Those are the Morse-SGC for the SCALE system, Heating 7.2, and KENO V.a. The manual describes the latest released versions of the codes

  3. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH.We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation.Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them.Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  4. Proteomic and functional analyses of the venom of Porthidium lansbergii lansbergii (Lansberg's hognose viper) from the Atlantic Department of Colombia.

    Science.gov (United States)

    Jiménez-Charris, Eliécer; Montealegre-Sanchez, Leonel; Solano-Redondo, Luis; Mora-Obando, Diana; Camacho, Erika; Castro-Herrera, Fernando; Fierro-Pérez, Leonardo; Lomonte, Bruno

    2015-01-30

    largely unknown. This study provides the first combined proteomic and functional analyses of the venom of this pitviper, which may contribute to a better understanding of the features of envenomings by this species. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. RNA-seq analyses reveal insights into the function of respiratory nitrate reductase of the diazotroph Herbaspirillum seropedicae.

    Science.gov (United States)

    Bonato, Paloma; Batista, Marcelo B; Camilios-Neto, Doumit; Pankievicz, Vânia C S; Tadra-Sfeir, Michelle Z; Monteiro, Rose Adele; Pedrosa, Fabio O; Souza, Emanuel M; Chubatsu, Leda S; Wassem, Roseli; Rigo, Liu Un

    2016-09-01

    Herbaspirillum seropedicae is a nitrogen-fixing β-proteobacterium that associates with roots of gramineous plants. In silico analyses revealed that H. seropedicae genome has genes encoding a putative respiratory (NAR) and an assimilatory nitrate reductase (NAS). To date, little is known about nitrate metabolism in H. seropedicae, and, as this bacterium cannot respire nitrate, the function of NAR remains unknown. This study aimed to investigate the function of NAR in H. seropedicae and how it metabolizes nitrate in a low aerated-condition. RNA-seq transcriptional profiling in the presence of nitrate allowed us to pinpoint genes important for nitrate metabolism in H. seropedicae, including nitrate transporters and regulatory proteins. Additionally, both RNA-seq data and physiological characterization of a mutant in the catalytic subunit of NAR (narG mutant) showed that NAR is not required for nitrate assimilation but is required for: (i) production of high levels of nitrite, (ii) production of NO and (iii) dissipation of redox power, which in turn lead to an increase in carbon consumption. In addition, wheat plants showed an increase in shoot dry weight only when inoculated with H. seropedicae wild type, but not with the narG mutant, suggesting that NAR is important to H. seropedicae-wheat interaction. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  6. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Directory of Open Access Journals (Sweden)

    Guan-Feng Wang

    2015-02-01

    Full Text Available Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR. Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC, a nucleotide binding (NB-ARC and a leucine rich repeat (LRR domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  7. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Science.gov (United States)

    Wang, Guan-Feng; Ji, Jiabing; El-Kasmi, Farid; Dangl, Jeffery L; Johal, Guri; Balint-Kurti, Peter J

    2015-02-01

    Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR) proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR). Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC), a nucleotide binding (NB-ARC) and a leucine rich repeat (LRR) domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  8. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes.

    Science.gov (United States)

    Baxter, Melissa; Withey, Sarah; Harrison, Sean; Segeritz, Charis-Patricia; Zhang, Fang; Atkinson-Dell, Rebecca; Rowe, Cliff; Gerrard, Dave T; Sison-Young, Rowena; Jenkins, Roz; Henry, Joanne; Berry, Andrew A; Mohamet, Lisa; Best, Marie; Fenwick, Stephen W; Malik, Hassan; Kitteringham, Neil R; Goldring, Chris E; Piper Hanley, Karen; Vallier, Ludovic; Hanley, Neil A

    2015-03-01

    Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Defining a procedure for predicting the duration of the approximately isothermal segments within the proposed drying regime as a function of the drying air parameters

    Science.gov (United States)

    Vasić, M.; Radojević, Z.

    2017-08-01

    One of the main disadvantages of the recently reported method, for setting up the drying regime based on the theory of moisture migration during drying, lies in a fact that it is based on a large number of isothermal experiments. In addition each isothermal experiment requires the use of different drying air parameters. The main goal of this paper was to find a way how to reduce the number of isothermal experiments without affecting the quality of the previously proposed calculation method. The first task was to define the lower and upper inputs as well as the output of the “black box” which will be used in the Box-Wilkinson’s orthogonal multi-factorial experimental design. Three inputs (drying air temperature, humidity and velocity) were used within the experimental design. The output parameter of the model represents the time interval between any two chosen characteristic points presented on the Deff - t. The second task was to calculate the output parameter for each planed experiments. The final output of the model is the equation which can predict the time interval between any two chosen characteristic points as a function of the drying air parameters. This equation is valid for any value of the drying air parameters which are within the defined area designated with lower and upper limiting values.

  10. Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms: Prediction of Everyday Functioning by Impairments in Emotional Expression and Emotional Experience.

    Science.gov (United States)

    Harvey, Philip D; Khan, Anzalee; Keefe, Richard S E

    2017-12-01

    Background: Reduced emotional experience and expression are two domains of negative symptoms. The authors assessed these two domains of negative symptoms using previously developed Positive and Negative Syndrome Scale (PANSS) factors. Using an existing dataset, the authors predicted three different elements of everyday functioning (social, vocational, and everyday activities) with these two factors, as well as with performance on measures of functional capacity. Methods: A large (n=630) sample of people with schizophrenia was used as the data source of this study. Using regression analyses, the authors predicted the three different aspects of everyday functioning, first with just the two Positive and Negative Syndrome Scale factors and then with a global negative symptom factor. Finally, we added neurocognitive performance and functional capacity as predictors. Results: The Positive and Negative Syndrome Scale reduced emotional experience factor accounted for 21 percent of the variance in everyday social functioning, while reduced emotional expression accounted for no variance. The total Positive and Negative Syndrome Scale negative symptom factor accounted for less variance (19%) than the reduced experience factor alone. The Positive and Negative Syndrome Scale expression factor accounted for, at most, one percent of the variance in any of the functional outcomes, with or without the addition of other predictors. Implications: Reduced emotional experience measured with the Positive and Negative Syndrome Scale, often referred to as "avolition and anhedonia," specifically predicted impairments in social outcomes. Further, reduced experience predicted social impairments better than emotional expression or the total Positive and Negative Syndrome Scale negative symptom factor. In this cross-sectional study, reduced emotional experience was specifically related with social outcomes, accounting for essentially no variance in work or everyday activities, and being the

  11. Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou; Kobe, Bostjan

    2017-04-06

    Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65 Åand 2.75 Å respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).

  12. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules F1-F8

    International Nuclear Information System (INIS)

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with eight of the functional modules in the code. Those are: BONAMI - resonance self-shielding by the Bondarenko method; NITAWL-II - SCALE system module for performing resonance shielding and working library production; XSDRNPM - a one-dimensional discrete-ordinates code for transport analysis; XSDOSE - a module for calculating fluxes and dose rates at points outside a shield; KENO IV/S - an improved monte carlo criticality program; COUPLE; ORIGEN-S - SCALE system module to calculate fuel depletion, actinide transmutation, fission product buildup and decay, and associated radiation source terms; ICE

  13. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation: Functional modules F1-F8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This Manual represents Revision 5 of the user documentation for the modular code system referred to as SCALE. The history of the SCALE code system dates back to 1969 when the current Computational Physics and Engineering Division at Oak Ridge National Laboratory (ORNL) began providing the transportation package certification staff at the U.S. Atomic Energy Commission with computational support in the use of the new KENO code for performing criticality safety assessments with the statistical Monte Carlo method. From 1969 to 1976 the certification staff relied on the ORNL staff to assist them in the correct use of codes and data for criticality, shielding, and heat transfer analyses of transportation packages. However, the certification staff learned that, with only occasional use of the codes, it was difficult to become proficient in performing the calculations often needed for an independent safety review. Thus, shortly after the move of the certification staff to the U.S. Nuclear Regulatory Commission (NRC), the NRC staff proposed the development of an easy-to-use analysis system that provided the technical capabilities of the individual modules with which they were familiar. With this proposal, the concept of the Standardized Computer Analyses for Licensing Evaluation (SCALE) code system was born. This volume consists of the section of the manual dealing with eight of the functional modules in the code. Those are: BONAMI - resonance self-shielding by the Bondarenko method; NITAWL-II - SCALE system module for performing resonance shielding and working library production; XSDRNPM - a one-dimensional discrete-ordinates code for transport analysis; XSDOSE - a module for calculating fluxes and dose rates at points outside a shield; KENO IV/S - an improved monte carlo criticality program; COUPLE; ORIGEN-S - SCALE system module to calculate fuel depletion, actinide transmutation, fission product buildup and decay, and associated radiation source terms; ICE.

  14. Functional connectivity of coral reef fishes in a tropical seascape assessed by compound-specific stable isotope analyses

    KAUST Repository

    McMahon, Kelton W.

    2011-01-01

    The ecological integrity of tropical habitats, including mangroves, seagrass beds and coral reefs, is coming under increasing pressure from human activities. Many coral reef fish species are thought to use mangroves and seagrass beds as juvenile nurseries before migrating to coral reefs as adults. Identifying essential habitats and preserving functional linkages among these habitats is likely necessary to promote ecosystem health and sustainable fisheries on coral reefs. This necessitates quantitative assessment of functional connectivity among essential habitats at the seascape level. This thesis presents the development and first application of a method for tracking fish migration using amino acid (AA) δ13C analysis in otoliths. In a controlled feeding experiment with fish reared on isotopically distinct diets, we showed that essential AAs exhibited minimal trophic fractionation between consumer and diet, providing a δ13C record of the baseline isoscape. We explored the potential for geochemical signatures in otoliths of snapper to act as natural tags of residency in seagrass beds, mangroves and coral reefs in the Red Sea, Caribbean Sea and Eastern Pacific Ocean. The δ13C values of otolith essential AAs varied as a function of habitat type and provided a better tracer of residence in juvenile nursery habitats than conventional bulk stable isotope analyses (SIA). Using our otolith AA SIA approach, we quantified the relative contribution of coastal wetlands and reef habitats to Lutjanus ehrenbergii populations on coastal, shelf and oceanic coral reefs in the Red Sea. L. ehrenbergii made significant ontogenetic migrations, traveling more than 30 km from juvenile nurseries to coral reefs and across deep open water. Coastal wetlands were important nurseries for L. ehrenbergii; however, there was significant plasticity in L. ehrenbergii juvenile habitat requirements. Seascape configuration played an important role in determining the functional connectivity of L

  15. Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Kozo Nagai

    Full Text Available BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs in Japanese patients with FHL. DESIGN AND METHODS: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. RESULTS: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2 and UNC13D mutation was in 10 (FHL3. In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5. Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. CONCLUSIONS: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s responsible for FHL remain to be identified.

  16. Modeling Asymmetric Flow of Viscoelastic Fluid in Symmetric Planar Sudden Expansion Geometry Based on User-Defined Function in FLUENT CFD Package

    Directory of Open Access Journals (Sweden)

    Zhi-Ying Zheng

    2013-01-01

    Full Text Available Through embedding an in-house subroutine into FLUENT code by utilizing the functionalization of user-defined function provided by the software, a new numerical simulation methodology on viscoelastic fluid flows has been established. In order to benchmark this methodology, numerical simulations under different viscoelastic fluid solution concentrations (with solvent viscosity ratio varied from 0.2 to 0.9, extensibility parameters (100≤L2≤500, Reynolds numbers (0.1 ≤ Re ≤ 100, and Weissenberg numbers (0 ≤ Wi ≤ 20 are conducted on unsteady laminar flows through a symmetric planar sudden expansion with expansion ratio of 1: 3 for viscoelastic fluid flows. The constitutive model used to describe the viscoelastic effect of viscoelastic fluid flow is FENE-P (finitely extensive nonlinear elastic-Peterlin model. The numerical simulation results show that the influences of elasticity, inertia, and concentration on the flow bifurcation characteristics are more significant than those of extensibility. The present simulation results including the critical Reynolds number for which the flow becomes asymmetric, vortex size, bifurcation diagram, velocity distribution, streamline, and pressure loss show good agreements with some published results. That means the newly established method based on FLUENT software platform for simulating peculiar flow behaviors of viscoelastic fluid is credible and suitable for the study of viscoelastic fluid flows.

  17. Effects of Red Wine Vinegar Beverage on the Colonic Tissue of Rodents: Biochemical, Functional and Pharmacological Analyses.

    Science.gov (United States)

    Enkhsaikhan, Azjargal; Takahara, Akira; Nakamura, Yuji; Goto, Ai; Chiba, Koki; Lubna, Nur Jaharat; Hagiwara-Nagasawa, Mihoko; Izumi-Nakaseko, Hiroko; Ando, Kentaro; Naito, Atsuhiko T; Sugiyama, Atsushi

    2018-01-01

    A beverage made of red wine vinegar and grape juice (Yamanashi-no-megumi™) was developed as a supplemental fluid containing polyphenols, which has been clinically shown to enhance the colonic transit. In this study, we assessed the mechanism of its prokinetic action by analyzing the effects on both the colonic phosphodiesterase activity of rats (n=4) and the isolated colonic strip preparation of guinea pigs (n=4). The 7% (v/v) solution of the beverage significantly decreased the phosphodiesterase activity by 9% (n=4). The beverage in concentrations of 0.7, 2.1 and 7% (v/v) relaxed the colonic strips pre-contracted by 1 µmol/L of carbachol in a concentration-related manner with 50, 58 and 79%, each response of which was diminished to 11, 19 and 46%, respectively in the presence of 100 µmol/L of L-nitro-arginine methyl ester. These results obtained by biochemical, functional and pharmacological analyses suggest that the beverage could relax the colon through both cAMP-associated and nitric oxide-dependent pathways, which may partly explain clinically observed prokinetic effect of the beverage.

  18. Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease.

    Science.gov (United States)

    Liu, Shiming; Su, Zhaobing; Tan, Sainan; Ni, Bin; Pan, Hong; Liu, Beihong; Wang, Jing; Xiao, Jianmin; Chen, Qiuhong

    2017-08-01

    CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.

  19. Software Defined Cyberinfrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Foster, Ian; Blaiszik, Ben; Chard, Kyle; Chard, Ryan

    2017-07-17

    Within and across thousands of science labs, researchers and students struggle to manage data produced in experiments, simulations, and analyses. Largely manual research data lifecycle management processes mean that much time is wasted, research results are often irreproducible, and data sharing and reuse remain rare. In response, we propose a new approach to data lifecycle management in which researchers are empowered to define the actions to be performed at individual storage systems when data are created or modified: actions such as analysis, transformation, copying, and publication. We term this approach software-defined cyberinfrastructure because users can implement powerful data management policies by deploying rules to local storage systems, much as software-defined networking allows users to configure networks by deploying rules to switches.We argue that this approach can enable a new class of responsive distributed storage infrastructure that will accelerate research innovation by allowing any researcher to associate data workflows with data sources, whether local or remote, for such purposes as data ingest, characterization, indexing, and sharing. We report on early experiments with this approach in the context of experimental science, in which a simple if-trigger-then-action (IFTA) notation is used to define rules.

  20. 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.

  1. Supraspliceosomes at Defined Functional States Portray the Pre-Assembled Nature of the Pre-mRNA Processing Machine in the Cell Nucleus

    Directory of Open Access Journals (Sweden)

    Hani Kotzer-Nevo

    2014-06-01

    Full Text Available When isolated from mammalian cell nuclei, all nuclear pre-mRNAs are packaged in multi-subunit large ribonucleoprotein complexes—supraspliceosomes—composed of four native spliceosomes interconnected by the pre-mRNA. Supraspliceosomes contain all five spliceosomal U snRNPs, together with other splicing factors, and are functional in splicing. Supraspliceosomes studied thus far represent the steady-state population of nuclear pre-mRNAs that were isolated at different stages of the splicing reaction. To analyze specific splicing complexes, here, we affinity purified Pseudomonas aeruginosa phage 7 (PP7-tagged splicing complexes assembled in vivo on Adenovirus Major Late (AdML transcripts at specific functional stages, and characterized them using molecular techniques including mass spectrometry. First, we show that these affinity purified splicing complexes assembled on PP7-tagged AdML mRNA or on PP7-tagged AdML pre-mRNA are assembled in supraspliceosomes. Second, similar to the general population of supraspliceosomes, these defined supraspliceosomes populations are assembled with all five U snRNPs at all splicing stages. This study shows that dynamic changes in base-pairing interactions of U snRNA:U snRNA and U snRNA:pre-mRNA that occur in vivo during the splicing reaction do not require changes in U snRNP composition of the supraspliceosome. Furthermore, there is no need to reassemble a native spliceosome for the splicing of each intron, and rearrangements of the interactions will suffice.

  2. Mediational Analyses of the Effects of Responsive Teaching on the Developmental Functioning of Preschool Children with Disabilities

    Science.gov (United States)

    Karaaslan, Ozcan; Mahoney, Gerald

    2015-01-01

    Mediational analyses were conducted with data from two small randomized control trials of the Responsive Teaching (RT) parent-mediated developmental intervention which used nearly identical intervention and control procedures. The purpose of these analyses was to determine whether or how the changes in maternal responsiveness and children's…

  3. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

    OpenAIRE

    Tweedy, J; Spyrou, MA; Pearson, M; Lassner, D; Kuhl, U; Gompels, UA

    2016-01-01

    Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, imp...

  4. Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.

    Science.gov (United States)

    Pérez-Cruz, M; Cruz-Lemini, M; Fernández, M T; Parra, J A; Bartrons, J; Gómez-Roig, M D; Crispi, F; Gratacós, E

    2015-10-01

    Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was  95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001). Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  5. Defining the mobilome.

    Science.gov (United States)

    Siefert, Janet L

    2009-01-01

    This chapter defines the agents that provide for the movement of genetic material which fuels the adaptive potential of life on our planet. The chapter has been structured to be broadly comprehensive, arbitrarily categorizing the mobilome into four classes: (1) transposons, (2) plasmids, (3) bacteriophage, and (4) self-splicing molecular parasites.Our increasing understanding of the mobilome is as dynamic as the mobilome itself. With continuing discovery, it is clear that nature has not confined these genomic agents of change to neat categories, but rather the classification categories overlap and intertwine. Massive sequencing efforts and their published analyses are continuing to refine our understanding of the extent of the mobilome. This chapter provides a framework to describe our current understanding of the mobilome and a foundation on which appreciation of its impact on genome evolution can be understood.

  6. No effects of functional exercise therapy on walking biomechanics in patients with knee osteoarthritis: exploratory outcome analyses from a randomised trial

    OpenAIRE

    Henriksen, Marius; Klokker, Louise; Bartholdy, Cecilie; Schjoedt-Jorgensen, Tanja; Bandak, Elisabeth; Bliddal, Henning

    2017-01-01

    Aim To assess the effects of a functional and individualised exercise programme on gait biomechanics during walking in people with knee OA. Methods Sixty participants were randomised to 12 weeks of facility-based functional and individualised neuromuscular exercise therapy (ET), 3 sessions per week supervised by trained physical therapists, or a no attention control group (CG). Three-dimensional gait analyses were used, from which a comprehensive list of conventional gait variables were extra...

  7. Analyses of the influencing factors of soil microbial functional gene diversity in tropical rainforest based on GeoChip 5.0.

    Science.gov (United States)

    Cong, Jing; Liu, Xueduan; Lu, Hui; Xu, Han; Li, Yide; Deng, Ye; Li, Diqiang; Zhang, Yuguang

    2015-09-01

    To examine soil microbial functional gene diversity and causative factors in tropical rainforests, we used a microarray-based metagenomic tool named GeoChip 5.0 to profile it. We found that high microbial functional gene diversity and different soil microbial metabolic potential for biogeochemical processes were considered to exist in tropical rainforest. Soil available nitrogen was the most associated with soil microbial functional gene structure. Here, we mainly describe the experiment design, the data processing, and soil biogeochemical analyses attached to the study in details, which could be published on BMC microbiology Journal in 2015, whose raw data have been deposited in NCBI's Gene Expression Omnibus (accession number GSE69171).

  8. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    Science.gov (United States)

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

    2015-01-01

    Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

  9. A methodology for evaluating weighting functions using MCNP and its application to PWR ex-core analyses

    International Nuclear Information System (INIS)

    Pecchia, Marco; Vasiliev, Alexander; Ferroukhi, Hakim; Pautz, Andreas

    2017-01-01

    Highlights: • Evaluation of neutron source importance for a given tally. • Assessment of ex-core detector response plus its uncertainty. • Direct use of neutron track evaluated by a Monte Carlo neutron transport code. - Abstract: The ex-core neutron detectors are commonly used to control reactor power in light water reactors. Therefore, it is relevant to understand the importance of a neutron source to the ex-core detectors response. In mathematical terms, this information is conveniently represented by the so called weighting functions. A new methodology based on the MCNP code for evaluating the weighting functions starting from the neutron history database is presented in this work. A simultaneous evaluation of the weighting functions in a user-given Cartesian coverage mesh is the main advantage of the method. The capability to generate weighting functions simultaneously in both spatial and energy ranges is the innovative part of this work. Then, an interpolation tool complements the methodology, allowing the generation of weighting functions up to the pin-by-pin fuel segment, where a direct evaluation is not possible due to low statistical precision. A comparison to reference results provides a verification of the methodology. Finally, an application to investigate the role of ex-core detectors spatial location and core burnup for a Swiss nuclear power plant is provided.

  10. High resolution crustal structure for the region between the Chilenia and Cuyania terrane above the Pampean flat slab of Argentina from local receiver function and petrological analyses

    Science.gov (United States)

    Ammirati, J. B.; Alvarado, P. M.; Pérez, S. B.; Beck, S. L.; Porter, R. C.; Zandt, G.

    2015-12-01

    Jean-Baptiste Ammirati 1,Sofía Perez 1, Patricia Alvarado 1, Susan L. Beck 2, Ryan Porter 3 and George Zandt 2(1) CIGEOBIO-CONICET, Universidad Nacional de San Juan, Argentina (2) The University of Arizona, USA (3) Northern Arizona University, USA At ~31ºS, The subduction of the Nazca plate under the South American plate presents along-strike variations of its dip angle referred to the Chilean-Pampean flat slab. Geological observations suggest that the regional crustal structure is inherited from the accretion of different terranes at Ordovician times and later reactivated during Andean compression since Miocene. Geophysical observations confirmed that the structure is extending in depth with décollement levels that accommodate crustal shortening in the region. In order to get a better insight on the shallow tectonics we computed high frequency local receiver functions from slab seismicity (~100 km depth). Local earthquakes present a higher frequency content that permits a better vertical resolution. Using a common conversion point (CCP) stacking method we obtained cross sections showing high-resolution crustal structure in the western part of the Pampean flat slab region, at the transition between the Precordillera and the Frontal Cordillera. Our results show a well-defined structure and their lateral extent for both units down to 80 km depth. In good agreement with previous studies, our higher resolution images better identify very shallow discontinuities putting more constraints on the relationships with the regional structural geology. Recent petrological analyses combined with RF high-resolution structure also allow us to better understand the regional crustal composition. Interestingly, we are able to observe a shifting structure beneath the Uspallata-Calingasta Valley, highlighting the differences in terms of crustal structure between the Precordillera and the Frontal Cordillera. Previously determined focal mechanisms in the region match well this

  11. Petrologic, morphologic and functional analyses of ground and abrasive stone tools from Rug Bair, Ovche Pole valley

    International Nuclear Information System (INIS)

    Boev, Blazho; Dimitrovska, Vasilka

    2011-01-01

    This paper represents the results of the ground and abrasive stone tools analyses based on the finds collected during the excavation of Rug Bair undertaken in 1970, and today stored in the Museum and Institute for Protection of Shtip. The studies were made possible with the help from the Faculty of Natural and Technical Sciences, Shtip, Republic of Macedonia. Through the stone material, an attempt was made a more comprehensive picture of the raw material, petrologic, technical and typo logical characteristics of the Neolithic stone industry at this site to be gained as well as its relationship with related simultaneously industries. (Author)

  12. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    OpenAIRE

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark; Kou, Zhifeng

    2015-01-01

    Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were pr...

  13. Analyses of advanced rice anther transcriptomes reveal global tapetum secretory functions and potential proteins for lipid exine formation.

    Science.gov (United States)

    Huang, Ming-Der; Wei, Fu-Jin; Wu, Cheng-Cheih; Hsing, Yue-Ie Caroline; Huang, Anthony H C

    2009-02-01

    The anthers in flowers perform important functions in sexual reproduction. Several recent studies used microarrays to study anther transcriptomes to explore genes controlling anther development. To analyze the secretion and other functions of the tapetum, we produced transcriptomes of anthers of rice (Oryza sativa subsp. japonica) at six progressive developmental stages and pollen with sequencing-by-synthesis technology. The transcriptomes included at least 18,000 unique transcripts, about 25% of which had antisense transcripts. In silico anther-minus-pollen subtraction produced transcripts largely unique to the tapetum; these transcripts include all the reported tapetum-specific transcripts of orthologs in other species. The differential developmental profiles of the transcripts and their antisense transcripts signify extensive regulation of gene expression in the anther, especially the tapetum, during development. The transcriptomes were used to dissect two major cell/biochemical functions of the tapetum. First, we categorized and charted the developmental profiles of all transcripts encoding secretory proteins present in the cellular exterior; these transcripts represent about 12% and 30% of the those transcripts having more than 100 and 1,000 transcripts per million, respectively. Second, we successfully selected from hundreds of transcripts several transcripts encoding potential proteins for lipid exine synthesis during early anther development. These proteins include cytochrome P450, acyltransferases, and lipid transfer proteins in our hypothesized mechanism of exine synthesis in and export from the tapetum. Putative functioning of these proteins in exine formation is consistent with proteins and metabolites detected in the anther locule fluid obtained by micropipetting.

  14. Defining nodes in complex brain networks

    Directory of Open Access Journals (Sweden)

    Matthew Lawrence Stanley

    2013-11-01

    Full Text Available Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel. The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10-20 millimeter diameter spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the correct method to be used remains an open, possibly unsolvable question that

  15. AGROBEST: an efficient Agrobacterium-mediated transient expression method for versatile gene function analyses in Arabidopsis seedlings

    Science.gov (United States)

    2014-01-01

    Background Transient gene expression via Agrobacterium-mediated DNA transfer offers a simple and fast method to analyze transgene functions. Although Arabidopsis is the most-studied model plant with powerful genetic and genomic resources, achieving highly efficient and consistent transient expression for gene function analysis in Arabidopsis remains challenging. Results We developed a highly efficient and robust Agrobacterium-mediated transient expression system, named AGROBEST (Agrobacterium-mediated enhanced seedling transformation), which achieves versatile analysis of diverse gene functions in intact Arabidopsis seedlings. Using β-glucuronidase (GUS) as a reporter for Agrobacterium-mediated transformation assay, we show that the use of a specific disarmed Agrobacterium strain with vir gene pre-induction resulted in homogenous GUS staining in cotyledons of young Arabidopsis seedlings. Optimization with AB salts in plant culture medium buffered with acidic pH 5.5 during Agrobacterium infection greatly enhanced the transient expression levels, which were significantly higher than with two existing methods. Importantly, the optimized method conferred 100% infected seedlings with highly increased transient expression in shoots and also transformation events in roots of ~70% infected seedlings in both the immune receptor mutant efr-1 and wild-type Col-0 seedlings. Finally, we demonstrated the versatile applicability of the method for examining transcription factor action and circadian reporter-gene regulation as well as protein subcellular localization and protein–protein interactions in physiological contexts. Conclusions AGROBEST is a simple, fast, reliable, and robust transient expression system enabling high transient expression and transformation efficiency in Arabidopsis seedlings. Demonstration of the proof-of-concept experiments elevates the transient expression technology to the level of functional studies in Arabidopsis seedlings in addition to previous

  16. Estimation of an image derived input function with MR-defined carotid arteries in FDG-PET human studies using a novel partial volume correction method

    DEFF Research Database (Denmark)

    Sari, Hasan; Erlandsson, Kjell; Law, Ian

    2017-01-01

    Kinetic analysis of18F-fluorodeoxyglucose positron emission tomography data requires an accurate knowledge the arterial input function. The gold standard method to measure the arterial input function requires collection of arterial blood samples and is an invasive method. Measuring an image deriv...... input function (p > 0.12 for grey matter and white matter). Hence, the presented image derived input function extraction method can be a practical alternative to noninvasively analyze dynamic18F-fluorodeoxyglucose data without the need for blood sampling....

  17. The Triumph of Function over Form The Role of Analytic Philosophy in Planning and Analysing Modern Architecture

    Directory of Open Access Journals (Sweden)

    Borbala Jasz

    2017-07-01

    Full Text Available The most dominant dialectical succession of architectural thinking during the 20th Century was between form and function. The latter of these two modern ways of architectural thinking is based on the results of Carnapian Neopositivism. The keywords of this philosophical school, that are empiricism, logic, verification, unity of language and science, could still be applied to interpreting modern architecture. I will explain the antecedents and the first connection between analytic philosophy and architecture, and some characteristic points of their influence during the 20th Century: the triumph of function over form as analogous to triumph of analytic philosophy over metaphysics.After the theoretic grounding of the form-function debate, I am going to focus first on the characteristic appearance of form: the Façadism of Socialist Realism in the architecture of East-Central Europe. Second, I will explain that architectural tendencies of classical modernism did not disappear in this period, they were just hidden in case of public buildings or migrated to the industrial planning. Third, I am going to claim that after this socialist realist gap, the architectural theory and planning tendencies of the interwar period – especially the work of Le Corbusier – returned and continued.

  18. Some Generalized Lacunary statistically difference double semi-normed sequence spaces defined by Orlicz function - doi: 10.4025/actascitechnol.v35i1.15523

    Directory of Open Access Journals (Sweden)

    Ayhan Esi

    2013-01-01

    Full Text Available In this article, we have introduced the idea of statistically convergent generalized difference lacunary double sequence spaces [¯w2 (M, Δn, p,q]θ, [¯w2 (M, Δn, p,q]θ and defined over a semi norm space (X, q. Also we have study some basic properties and obtained some inclusion relations between them.  

  19. Transcriptomic and Functional Analyses Reveal That PpGLK1 Regulates Chloroplast Development in Peach (Prunus persica

    Directory of Open Access Journals (Sweden)

    Min Chen

    2018-01-01

    Full Text Available Peach is an ideal species for fruit tree research because of its small, fully sequenced genome. Chloroplast development is dependent on the tight cooperation between the nuclear and plastid genomes, and is regulated by GLK transcription factors. In this work, the pigment content was monitored and the chloroplast-to-chromoplast conversion during the fruit ripening was visualized by transmission electron microscopy. Localization and expression analyses showed that PpGLK1 was located in the nucleus and expressed mainly in the leaves and fruit skin. A transcriptome analysis showed that PpGLK1 and its target genes were significantly differentially expressed in ripening peach fruit skin. PpGLK1 silencing affected chlorophyll accumulation in peach leaves and fruits. Overexpression of PpGLK1 rescued the phenotypes of the Arabidopsis Atglk1Atglk2 double mutant and the tomato uniform ripening mutant. The results of a yeast two-hybrid analysis showed that PpGLK1 is autoactivated and that PpGLK1 (301-542 a.a. interacted with PpARF5. Together, our results indicate that PpGLK1 regulates chloroplast development in green tissues in peach. Therefore, it may be a promising target gene for improving the production and quality of peach by genetic engineering and breeding approaches.

  20. Socio-sexual functioning in autism spectrum disorder: A systematic review and meta-analyses of existing literature.

    Science.gov (United States)

    Hancock, Grace I P; Stokes, Mark A; Mesibov, Gary B

    2017-11-01

    Socio-sexual functioning encompasses an individual's interests, behaviors, and knowledge with respect to sexual, romantic, and social aspects of life. An individual's understanding of these domains is developed through a range of informal and formal avenues of sexual health education. The current model demonstrated this and proposed that, compared to typically developing individuals, those with ASD develop socio-sexual functioning differently due to having less peer engagement, less relationship experience, more parental guidance, greater use of online materials, receive less school-based sexual health education, and more support from wellbeing services. Systematic review and meta-analysis of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior, are described as engaging in less appropriate sexual behavior, have greater concerns about themselves, and receive less sexual health education. Having fewer opportunities for appropriate informal and formal sexual health education leaves them at a double disadvantage from others who are receiving this information from both of these avenues. Some of the current meta-analytic results are cautioned by large l-square statistics which suggest that a degree of variance is being caused by extraneous factors. Further empirical research in this area is needed to overcome current design and sample limitations. Finally, the Sexual Behavior Scale was the most commonly utilized tool in the meta-analyzed studies, thus comprehensive evaluation of its functioning is warranted. The importance of work in this area is highlighted by the central role of social and sexual wellbeing on one's quality of life. Autism Res 2017, 10: 1823-1833. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Review of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior

  1. The Pectin Methylesterase Gene Complement of Phytophthora sojae: Structural and Functional Analyses, and the Evolutionary Relationships with Its Oomycete Homologs.

    Science.gov (United States)

    Horowitz, Brent B; Ospina-Giraldo, Manuel D

    2015-01-01

    Phytophthora sojae is an oomycete pathogen that causes the disease known as root and stem rot in soybean plants, frequently leading to massive economic damage. Additionally, P. sojae is increasingly being utilized as a model for phytopathogenic oomycete research. Despite the economic and scientific importance of P. sojae, the mechanism by which it penetrates the host roots is not yet fully understood. It has been found that oomycetes are not capable of penetrating the cell wall solely through mechanical force, suggesting that alternative factors facilitate breakdown of the host cell wall. Pectin methylesterases have been suggested to be important for Phytophthora pathogenicity, but no data exist on their role in the P. sojae infection process. We have scanned the newly revised version of the annotated P. sojae genome for the presence of putative pectin methylesterases genes and conducted a sequence analysis of all gene models found. We also searched for potential regulatory motifs in the promoter region of the proposed P. sojae models, and investigated the gene expression levels throughout the early course of infection on soybean plants. We found that P. sojae contains a large repertoire of pectin methylesterase-coding genes and that most of these genes display similar motifs in the promoter region, indicating the possibility of a shared regulatory mechanism. Phylogenetic analyses confirmed the evolutionary relatedness of the pectin methylesterase-coding genes within and across Phytophthora spp. In addition, the gene duplication events that led to the emergence of this gene family appear to have occurred prior to many speciation events in the genus Phytophthora. Our results also indicate that the highest levels of expression occurred in the first 24 hours post inoculation, with expression falling after this time. Our study provides evidence that pectin methylesterases may be important for the early action of the P. sojae infection process.

  2. The Pectin Methylesterase Gene Complement of Phytophthora sojae: Structural and Functional Analyses, and the Evolutionary Relationships with Its Oomycete Homologs.

    Directory of Open Access Journals (Sweden)

    Brent B Horowitz

    Full Text Available Phytophthora sojae is an oomycete pathogen that causes the disease known as root and stem rot in soybean plants, frequently leading to massive economic damage. Additionally, P. sojae is increasingly being utilized as a model for phytopathogenic oomycete research. Despite the economic and scientific importance of P. sojae, the mechanism by which it penetrates the host roots is not yet fully understood. It has been found that oomycetes are not capable of penetrating the cell wall solely through mechanical force, suggesting that alternative factors facilitate breakdown of the host cell wall. Pectin methylesterases have been suggested to be important for Phytophthora pathogenicity, but no data exist on their role in the P. sojae infection process. We have scanned the newly revised version of the annotated P. sojae genome for the presence of putative pectin methylesterases genes and conducted a sequence analysis of all gene models found. We also searched for potential regulatory motifs in the promoter region of the proposed P. sojae models, and investigated the gene expression levels throughout the early course of infection on soybean plants. We found that P. sojae contains a large repertoire of pectin methylesterase-coding genes and that most of these genes display similar motifs in the promoter region, indicating the possibility of a shared regulatory mechanism. Phylogenetic analyses confirmed the evolutionary relatedness of the pectin methylesterase-coding genes within and across Phytophthora spp. In addition, the gene duplication events that led to the emergence of this gene family appear to have occurred prior to many speciation events in the genus Phytophthora. Our results also indicate that the highest levels of expression occurred in the first 24 hours post inoculation, with expression falling after this time. Our study provides evidence that pectin methylesterases may be important for the early action of the P. sojae infection process.

  3. A functional approach for research on cognitive control: Analysing cognitive control tasks and their effects in terms of operant conditioning.

    Science.gov (United States)

    Liefooghe, Baptist; De Houwer, Jan

    2016-02-01

    Cognitive control is an important mental ability that is examined using a multitude of cognitive control tasks and effects. The present paper presents the first steps in the elaboration of a functional approach, which aims to uncover the communalities and differences between different cognitive control tasks and their effects. Based on the idea that responses in cognitive control tasks qualify as operant behaviour, we propose to reinterpret cognitive control tasks in terms of operant contingencies and cognitive control effects as instances of moderated stimulus control. We illustrate how our approach can be used to uncover communalities between topographically different cognitive control tasks and can lead to novel questions about the processes underlying cognitive control. © 2015 International Union of Psychological Science.

  4. Load time functions (LTF) for large commercial aircraft based on Riera approach and finite element analyses – a parametric study

    International Nuclear Information System (INIS)

    Iliev, A.

    2013-01-01

    Conclusions: In cases of a complex geometry of the target structure a careful evaluation of the predefined load time function should be performed. Special attention should be paid on different deceleration of airplane parts and their equivalent load forces. In cases of cylindrical structures with relatively small diameter (in comparison to the airplane wing spread), the impact of the engines should be investigated separately. When auxiliary structures are surrounding the reactor containment, the impact load will be reduced due to initial destruction of part of the airplane in the surrounding auxiliary structures. For the case study, this reduction was found to be non-significant. However if important equipment is situated in surrounding auxiliary buildings, engines may provide higher equivalent forces compared to normal planar target structure

  5. Defining the Interactions of Cellobiohydrolase with Substrate through Structure Function Studies: Cooperative Research and Development Final Report, CRADA Number CRD-10-409

    Energy Technology Data Exchange (ETDEWEB)

    Beckham, G. T.; Himmel, M. E.

    2013-07-01

    NREL researchers will use their expertise and skilled resources in numerical computational modeling to generate structure-function relationships for improved cellulase variant enzymes to support the development of cellulases with improved performance in biomass conversion.

  6. Aerodynamic and cephalometric analyses of velopharyngeal structure and function following re-pushback surgery for secondary correction in cleft palate.

    Science.gov (United States)

    Nakamura, Norifumi; Ogata, Yuko; Sasaguri, Masaaki; Suzuki, Akira; Kikuta, Rumiko; Ohishi, Masamichi

    2003-01-01

    The goal of this study was to clarify the efficacy of and indication for re-pushback surgery as secondary treatment for cleft palate. Fifteen patients treated by re-pushback surgery involving intravelar veloplasty (IVV) with buccal mucosal grafting on the nasal surface and followed up more than 6 months were enrolled in this study. Pre- and postoperative velopharyngeal functions were analyzed by perceptual voice analysis, blowing ratio, and nasalance scores during phonation of /i/ and /tsu/. Cephalometric analysis was used to evaluate the relationship between velopharyngeal structure and the outcome of re-pushback surgery. Control data were obtained from the longitudinal files of normal 10-year-old children in Kyushu University Dental Hospital. Eight of 15 patients obtained complete velopharyngeal closure (complete group), five patients improved remarkably (improved group), and no effective result was seen in two patients (ineffective group). Nasality disappeared or remarkably improved after the operation in 13 patients. Effective surgical results were found in 86.7% of the patients. Partial flap necrosis was seen in two patients in whom re-pushback surgery was performed using mucosal palatal flaps instead of mucoperiosteal flaps. Preoperative velar length and the length/depth ratio of the re-pushback group were significantly smaller than the controls, but there was no difference after the operation. Furthermore, the preoperative length/depth ratio of the complete group (ranged more than 100%) was significantly greater than those of the other two groups (ranged less than 100%). Re-pushback surgery by IVV with free mucous grafting on the nasal surface was effective in managing velopharyngeal incompetence secondarily, improving velopharyngeal structure and function.

  7. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses.

    Science.gov (United States)

    Gay, Charles W; Robinson, Michael E; Lai, Song; O'Shea, Andrew; Craggs, Jason G; Price, Donald D; Staud, Roland

    2016-02-01

    Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS). The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN). The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased. For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue. Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

  8. Mechanistic Insight into Bunyavirus-Induced Membrane Fusion from Structure-Function Analyses of the Hantavirus Envelope Glycoprotein Gc.

    Directory of Open Access Journals (Sweden)

    Pablo Guardado-Calvo

    2016-10-01

    Full Text Available Hantaviruses are zoonotic viruses transmitted to humans by persistently infected rodents, giving rise to serious outbreaks of hemorrhagic fever with renal syndrome (HFRS or of hantavirus pulmonary syndrome (HPS, depending on the virus, which are associated with high case fatality rates. There is only limited knowledge about the organization of the viral particles and in particular, about the hantavirus membrane fusion glycoprotein Gc, the function of which is essential for virus entry. We describe here the X-ray structures of Gc from Hantaan virus, the type species hantavirus and responsible for HFRS, both in its neutral pH, monomeric pre-fusion conformation, and in its acidic pH, trimeric post-fusion form. The structures confirm the prediction that Gc is a class II fusion protein, containing the characteristic β-sheet rich domains termed I, II and III as initially identified in the fusion proteins of arboviruses such as alpha- and flaviviruses. The structures also show a number of features of Gc that are distinct from arbovirus class II proteins. In particular, hantavirus Gc inserts residues from three different loops into the target membrane to drive fusion, as confirmed functionally by structure-guided mutagenesis on the HPS-inducing Andes virus, instead of having a single "fusion loop". We further show that the membrane interacting region of Gc becomes structured only at acidic pH via a set of polar and electrostatic interactions. Furthermore, the structure reveals that hantavirus Gc has an additional N-terminal "tail" that is crucial in stabilizing the post-fusion trimer, accompanying the swapping of domain III in the quaternary arrangement of the trimer as compared to the standard class II fusion proteins. The mechanistic understandings derived from these data are likely to provide a unique handle for devising treatments against these human pathogens.

  9. A systemic gene silencing method suitable for high throughput, reverse genetic analyses of gene function in fern gametophytes

    Directory of Open Access Journals (Sweden)

    Tanurdzic Milos

    2004-04-01

    Full Text Available Abstract Background Ceratopteris richardii is a useful experimental system for studying gametophyte development and sexual reproduction in plants. However, few tools for cloning mutant genes or disrupting gene function exist for this species. The feasibility of systemic gene silencing as a reverse genetics tool was examined in this study. Results Several DNA constructs targeting a Ceratopteris protoporphyrin IX magnesium chelatase (CrChlI gene that is required for chlorophyll biosynthesis were each introduced into young gametophytes by biolistic delivery. Their transient expression in individual cells resulted in a colorless cell phenotype that affected most cells of the mature gametophyte, including the meristem and gametangia. The colorless phenotype was associated with a 7-fold decrease in the abundance of the endogenous transcript. While a construct designed to promote the transient expression of a CrChlI double stranded, potentially hairpin-forming RNA was found to be the most efficient in systemically silencing the endogenous gene, a plasmid containing the CrChlI cDNA insert alone was sufficient to induce silencing. Bombarded, colorless hermaphroditic gametophytes produced colorless embryos following self-fertilization, demonstrating that the silencing signal could be transmitted through gametogenesis and fertilization. Bombardment of young gametophytes with constructs targeting the Ceratopteris filamentous temperature sensitive (CrFtsZ and uroporphyrin dehydrogenase (CrUrod genes also produced the expected mutant phenotypes. Conclusion A method that induces the systemic silencing of target genes in the Ceratopteris gametophyte is described. It provides a simple, inexpensive and rapid means to test the functions of genes involved in gametophyte development, especially those involved in cellular processes common to all plants.

  10. Survival of the most transferable at the top of Jacob's ladder: Defining and testing the ωB97M(2) double hybrid density functional

    Science.gov (United States)

    Mardirossian, Narbe; Head-Gordon, Martin

    2018-06-01

    A meta-generalized gradient approximation, range-separated double hybrid (DH) density functional with VV10 non-local correlation is presented. The final 14-parameter functional form is determined by screening trillions of candidate fits through a combination of best subset selection, forward stepwise selection, and random sample consensus (RANSAC) outlier detection. The MGCDB84 database of 4986 data points is employed in this work, containing a training set of 870 data points, a validation set of 2964 data points, and a test set of 1152 data points. Following an xDH approach, orbitals from the ωB97M-V density functional are used to compute the second-order perturbation theory correction. The resulting functional, ωB97M(2), is benchmarked against a variety of leading double hybrid density functionals, including B2PLYP-D3(BJ), B2GPPLYP-D3(BJ), ωB97X-2(TQZ), XYG3, PTPSS-D3(0), XYGJ-OS, DSD-PBEP86-D3(BJ), and DSD-PBEPBE-D3(BJ). Encouragingly, the overall performance of ωB97M(2) on nearly 5000 data points clearly surpasses that of all of the tested density functionals. As a Rung 5 density functional, ωB97M(2) completes our family of combinatorially optimized functionals, complementing B97M-V on Rung 3, and ωB97X-V and ωB97M-V on Rung 4. The results suggest that ωB97M(2) has the potential to serve as a powerful predictive tool for accurate and efficient electronic structure calculations of main-group chemistry.

  11. Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms: Prediction of Everyday Functioning by Impairments in Emotional Expression and Emotional Experience

    OpenAIRE

    Harvey, Philip D.; Khan, Anzalee; Keefe, Richard S. E.

    2017-01-01

    Background: Reduced emotional experience and expression are two domains of negative symptoms. The authors assessed these two domains of negative symptoms using previously developed Positive and Negative Syndrome Scale (PANSS) factors. Using an existing dataset, the authors predicted three different elements of everyday functioning (social, vocational, and everyday activities) with these two factors, as well as with performance on measures of functional capacity. Methods: A large (n=630) sampl...

  12. Rehabilitation of executive functioning with training in attention regulation applied to individually defined goals: a pilot study bridging theory, assessment, and treatment.

    Science.gov (United States)

    Novakovic-Agopian, Tatjana; Chen, Anthony J-W; Rome, Scott; Abrams, Gary; Castelli, Holli; Rossi, Annemarie; McKim, Ryan; Hills, Nancy; D'Esposito, Mark

    2011-01-01

    To assess feasibility and effects of training in goal-oriented attentional self-regulation for patients with brain injury and chronic executive dysfunction. Sixteen individuals with chronic brain injury and mild to moderate executive dysfunction. Participants were divided into 2 groups: one group completed goal-oriented attentional self-regulation training during the first 5 weeks, followed by a brief (2-hour) educational instruction session as a control midway through the second 5 weeks; the other group participated in reverse order. Neuropsychological and functional performance assessed at baseline and at weeks 5 and 10. Participants found training in goal-oriented attentional self-regulation engaging, incorporated some trained strategies into daily life, and reported subjective improvements in personal functioning. At week 5, participants who completed goals training significantly improved on tests of attention and executive function and had fewer functional task failures, while performance did not change after educational instruction. At week 10, participants who crossed over from educational instruction to goals training also significantly improved on attention and executive function tests. Participants who crossed from goals training to educational instruction maintained their week 5 gains. Training in goal-oriented attentional self-regulation is theoretically driven and feasible in a research setting. Pilot results suggest improvements in cognitive and functional domains targeted by the intervention.

  13. School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

    Science.gov (United States)

    Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

    2014-01-01

    The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

  14. School Belongingness and Mental Health Functioning across the Primary-Secondary Transition in a Mainstream Sample: Multi-Group Cross-Lagged Analyses

    Science.gov (United States)

    Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

    2014-01-01

    The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students’ school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students. PMID:24967580

  15. School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

  16. Functional and modular analyses of diverse endoglucanases from Ruminococcus albus 8, a specialist plant cell wall degrading bacterium.

    Science.gov (United States)

    Iakiviak, Michael; Devendran, Saravanan; Skorupski, Anna; Moon, Young Hwan; Mackie, Roderick I; Cann, Isaac

    2016-07-21

    Ruminococcus albus 8 is a specialist plant cell wall degrading ruminal bacterium capable of utilizing hemicellulose and cellulose. Cellulose degradation requires a suite of enzymes including endoglucanases, exoglucanases, and β-glucosidases. The enzymes employed by R. albus 8 in degrading cellulose are yet to be completely elucidated. Through bioinformatic analysis of a draft genome sequence of R. albus 8, seventeen putatively cellulolytic genes were identified. The genes were heterologously expressed in E. coli, and purified to near homogeneity. On biochemical analysis with cellulosic substrates, seven of the gene products (Ra0185, Ra0259, Ra0325, Ra0903, Ra1831, Ra2461, and Ra2535) were identified as endoglucanases, releasing predominantly cellobiose and cellotriose. Each of the R. albus 8 endoglucanases, except for Ra0259 and Ra0325, bound to the model crystalline cellulose Avicel, confirming functional carbohydrate binding modules (CBMs). The polypeptides for Ra1831 and Ra2535 were found to contain distantly related homologs of CBM65. Mutational analysis of residues within the CBM65 of Ra1831 identified key residues required for binding. Phylogenetic analysis of the endoglucanases revealed three distinct subfamilies of glycoside hydrolase family 5 (GH5). Our results demonstrate that this fibrolytic bacterium uses diverse GH5 catalytic domains appended with different CBMs, including novel forms of CBM65, to degrade cellulose.

  17. Comparative genomic and functional analyses: unearthing the diversity and specificity of nematicidal factors in Pseudomonas putida strain 1A00316

    Science.gov (United States)

    Guo, Jing; Jing, Xueping; Peng, Wen-Lei; Nie, Qiyu; Zhai, Yile; Shao, Zongze; Zheng, Longyu; Cai, Minmin; Li, Guangyu; Zuo, Huaiyu; Zhang, Zhitao; Wang, Rui-Ru; Huang, Dian; Cheng, Wanli; Yu, Ziniu; Chen, Ling-Ling; Zhang, Jibin

    2016-01-01

    We isolated Pseudomonas putida (P. putida) strain 1A00316 from Antarctica. This bacterium has a high efficiency against Meloidogyne incognita (M. incognita) in vitro and under greenhouse conditions. The complete genome of P. putida 1A00316 was sequenced using PacBio single molecule real-time (SMRT) technology. A comparative genomic analysis of 16 Pseudomonas strains revealed that although P. putida 1A00316 belonged to P. putida, it was phenotypically more similar to nematicidal Pseudomonas fluorescens (P. fluorescens) strains. We characterized the diversity and specificity of nematicidal factors in P. putida 1A00316 with comparative genomics and functional analysis, and found that P. putida 1A00316 has diverse nematicidal factors including protein alkaline metalloproteinase AprA and two secondary metabolites, hydrogen cyanide and cyclo-(l-isoleucyl-l-proline). We show for the first time that cyclo-(l-isoleucyl-l-proline) exhibit nematicidal activity in P. putida. Interestingly, our study had not detected common nematicidal factors such as 2,4-diacetylphloroglucinol (2,4-DAPG) and pyrrolnitrin in P. putida 1A00316. The results of the present study reveal the diversity and specificity of nematicidal factors in P. putida strain 1A00316. PMID:27384076

  18. Resurrecting Brinley Plots for a Novel Use: Meta-Analyses of Functional Brain Imaging Data in Older Adults

    Directory of Open Access Journals (Sweden)

    Ann M. Peiffer

    2008-01-01

    Full Text Available By plotting response times of young and older adults across a variety of tasks, Brinley spurred investigation and debate into the theory of general cognitive slowing. Though controversial, Brinley plots can assess between-task differences, the impact of increasing task demand, and the relationship between responses in two groups of subjects. Since a relationship exists between response times and the blood-oxygen level dependent (BOLD signal of functional MRI (fMRI, Brinley's plotting method could be applied as a meta-analysis tool in fMRI studies of aging. Here, fledgling “Peiffer plots” are discussed for their potential impact on understanding general cognitive brain activity in aging. Preliminary results suggest that general cognitive slowing may be localized at the sensorimotor transformation in the precentral gyrus. Although this meta-analysis method is naturally used with imaging studies of aging, theoretically it may be applied to other study pairs (e.g., schizophrenic versus normal or imaging datasets (e.g., PET.

  19. Genome-Wide Comparative Functional Analyses Reveal Adaptations of Salmonella sv. Newport to a Plant Colonization Lifestyle

    Directory of Open Access Journals (Sweden)

    Marcos H. de Moraes

    2018-05-01

    Full Text Available Outbreaks of salmonellosis linked to the consumption of vegetables have been disproportionately associated with strains of serovar Newport. We tested the hypothesis that strains of sv. Newport have evolved unique adaptations to persistence in plants that are not shared by strains of other Salmonella serovars. We used a genome-wide mutant screen to compare growth in tomato fruit of a sv. Newport strain from an outbreak traced to tomatoes, and a sv. Typhimurium strain from animals. Most genes in the sv. Newport strain that were selected during persistence in tomatoes were shared with, and similarly selected in, the sv. Typhimurium strain. Many of their functions are linked to central metabolism, including amino acid biosynthetic pathways, iron acquisition, and maintenance of cell structure. One exception was a greater need for the core genes involved in purine metabolism in sv. Typhimurium than in sv. Newport. We discovered a gene, papA, that was unique to sv. Newport and contributed to the strain’s fitness in tomatoes. The papA gene was present in about 25% of sv. Newport Group III genomes and generally absent from other Salmonella genomes. Homologs of papA were detected in the genomes of Pantoea, Dickeya, and Pectobacterium, members of the Enterobacteriacea family that can colonize both plants and animals.

  20. Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells

    International Nuclear Information System (INIS)

    Kim, Joon-Young; Kim, Han-Jong; Hurt, Elaine M.; Chen, Xin; Howard, O.M. Zack; Farrar, William L.

    2007-01-01

    FOXP3, a forkhead transcription factor is essential for the development and function of CD4 + CD25 + regulatory T cells (Tregs). In contrast to conversion of murine naive T cells to Tregs by transduction of Foxp3, it is controversial whether ectopic expression of FOXP3 in human CD4 + T cells is sufficient for acquisition of suppressive activity. Here, we show that retroviral transduction of FOXP3 induces a Treg phenotype in human leukemic CD4 + Jurkat-T cells, evidenced by increased expression of Treg-associated cell surface markers as well as inhibition of cytokine production. Furthermore, FOXP3-transduced Jurkat-T cells suppress the proliferation of human CD4 + CD25 - T cells. Additionally, DNA microarray analysis identifies Treg-related genes regulated by FOXP3. Our study demonstrates that enforced expression of FOXP3 confers Treg-like properties on Jurkat-T cells, which can be a convenient and efficient Treg-like cell model for further study to identify Treg cell surface markers and target genes regulated by FOXP3

  1. The physiological basis of Glottal electromagnetic micropower sensors (GEMS) and their use in defining an excitation function for the human vocal tract

    Science.gov (United States)

    Burnett, Gregory Clell

    1999-10-01

    The definition, use, and physiological basis of Glottal Electromagnetic Micropower Sensors (GEMS) is presented. These sensors are a new type of low power (excitation function for the human vocal tract. For the first time, an excitation function may be calculated in near real time using a noninvasive procedure. Several experiments and models are presented to demonstrate that the GEMS signal is representative of the motion of the subglottal posterior wall of the trachea as it vibrates in response to the pressure changes caused by the folds as they modulate the airflow supplied by the lungs. The vibrational properties of the tracheal wall are modeled using a lumped-element circuit model. Taking the output of the vocal tract to be the audio pressure captured by a microphone and the input to be the subglottal pressure, the transfer function of the vocal tract (including the nasal cavities) can be approximated every 10-30 milliseconds using an autoregressive moving-average model. Unlike the currently utilized method of transfer function approximation, this new method only involves noninvasive GEMS measurements and digital signal processing and does not demand the difficult task of obtaining precise physical measurements of the tract and subsequent estimation of the transfer function using its cross-sectional area. The ability to measure the physical motion of the trachea enables a significant number of potential applications, ranging from very accurate pitch detection to speech synthesis, speaker verification, and speech recognition.

  2. New MRI technologies. Diffusion MRI and its application to functional neuroimaging and analyses of white matter integrity

    International Nuclear Information System (INIS)

    Kobayashi, Tetsuo

    2010-01-01

    Described is the technological aspect of MRI, MR diffusion-weighted imaging (MR-DWI), principles of its measurement and application for imaging the cerebral function and for aiding the quantitative diagnosis of brain diseases. The author explains the principle of MR imaging process; diffusion properties of water molecules, MR-DWI based on them and DW-fMRI of the brain; MR-diffusion tensor imaging (MR-DTI), its analysis and color acquisition, and tracking of white matter nerve fibers; analysis of white matter lesions by the tracking; and the new tracking method at the chiasm of nerve fascicles. The usual fMRI reflects the blood oxygen level depending (BOLD) signals whereas recently attracted DW-fMRI, the volume changes of nerve cells concomitant to nerve activation accompanying apparent changes of water diffusion coefficients in and out of cells which occur faster than BOLD signs, resulting in higher resolution of time and space. However, DWI requires the higher intensity of static magnetic field like 3T. MR-DTI acquires the anisotropic diffusion of water molecules using MR-DWI technique with application of 6 or more motion probing gradients, thus makes it possible to track the running directions of nerve fibers and capillary vessels, and is proposed to be a useful mean of specific fiber tracking in the white matter when displayed by 3 different colors exhibiting the directions like the right/left (x axis, red), anterior/posterior (y, green) and upper/lower (z, blue) sides of head. Recently, MR-DWI and MR-DTI have been found usable for pathogenic studies of brain diseases such as dementia. Tensor anisotropy is apparently lowered at the chiasm of nerve fascicles, the cause of tracking error, for which authors have developed a new method using the similarity of directional vector, not of tensor, before and behind the chiasm. As exemplified, MRI technology is further advancing even at present. (T.T.)

  3. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).

    Science.gov (United States)

    Jochems, Caroline; Tritsch, Sarah R; Pellom, Samuel Troy; Su, Zhen; Soon-Shiong, Patrick; Wong, Hing C; Gulley, James L; Schlom, Jeffrey

    2017-09-26

    M7824 (MSB0011359C) is a novel first-in-class bifunctional fusion protein consisting of a fully human IgG1 anti-PD-L1 monoclonal antibody (with structural similarities to avelumab) linked to the extracellular domain of two TGFβ receptor 2 (TGFβR2) molecules serving as a TGFβ Trap. Avelumab has demonstrated clinical activity in a range of human cancers and has been approved by the Food and Drug Administration for the therapy of Merkel cell and bladder carcinomas. Preclinical studies have shown this anti-PD-L1 is capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). In the studies reported here, it is shown that M7824 is also capable of mediating ADCC of a wide range of human carcinoma cells in vitro , employing natural killer (NK) cells as effectors, albeit not as potent as anti-PD-L1 employing some tumor cells as targets. The addition of the IL-15 superagonist fusion protein complex ALT-803 enhanced the ADCC capacity of both anti-PD-L1 and M7824, and to levels that both agents now demonstrated similar levels of ADCC of tumor cells. TGFβ is a known immunosuppressive entity. Studies reported here show TGFβ1 induced reduction of several NK activation markers as well as reduction of endogenous NK lytic activity and NK-mediated ADCC of tumor cells. These phenomena could be reduced or mitigated, however, by M7824, but not by anti-PD-L1. M7824, but not anti-PD-L1, was also shown to reduce the immunosuppressive activity of regulatory T cells on human CD4 + T-cell proliferation. These studies thus demonstrate the dual functionalities of M7824 and provide the rationale for its further clinical development.

  4. Synthesis and functions of well-defined polymer-drug conjugates as efficient nanocarriers for intravesical chemotherapy of bladder cancer(a).

    Science.gov (United States)

    Yu, Qingsong; Zhang, Jiajing; Zhang, Guan; Gan, Zhihua

    2015-04-01

    Novel poly(ethylene glycol) and poly(N-(2-hydroxypropyl)methacrylamide) block copolymer (PEG-b-PHPMA) with well-defined composition was synthesized by RAFT polymerization. Folate and doxorubicin (DOX) were quantitatively introduced into the copolymer. The influences of folate content and pH value on folate receptor (FR) mediated cell endocytosis and pH-responsive DOX release were studied. It has been demonstrated that minimum folate content is needed for the enrichment of hydrophobic folate on the hydrophilic part of polymer conjugates. The cytotoxicity of targetable polymer drug conjugates was much higher than that of non-targetable ones and free DOX. It could be concluded that the folate plays a significant role in targeting and internalization of the conjugates against bladder cancer cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Analyses of the influencing factors of soil microbial functional gene diversity in tropical rainforest based on GeoChip 5.0

    Directory of Open Access Journals (Sweden)

    Jing Cong

    2015-09-01

    Full Text Available To examine soil microbial functional gene diversity and causative factors in tropical rainforests, we used a microarray-based metagenomic tool named GeoChip 5.0 to profile it. We found that high microbial functional gene diversity and different soil microbial metabolic potential for biogeochemical processes were considered to exist in tropical rainforest. Soil available nitrogen was the most associated with soil microbial functional gene structure. Here, we mainly describe the experiment design, the data processing, and soil biogeochemical analyses attached to the study in details, which could be published on BMC microbiology Journal in 2015, whose raw data have been deposited in NCBI's Gene Expression Omnibus (accession number GSE69171.

  6. Phenotypic and functional analyses of NK and NKT-like populations during the early stages of chikungunya infection.

    Science.gov (United States)

    Thanapati, Subrat; Das, Rumki; Tripathy, Anuradha S

    2015-01-01

    The aim of this study was to characterize NK (CD56(+)CD3(-)) and NKT-like cell (CD56(+)CD3(+)) responses early after chikungunya infection. Expression profiling and functional analysis of T/NK/NKT-like cells were performed on samples from 56 acute and 31 convalescent chikungunya patients and 56 control individuals. The percentages of NK cells were high in both patient groups, whereas NKT-like cell percentages were high only in the convalescent group. The percentages of NKp30(+)CD3(-)CD56(+), NKp30(+)CD3(+)CD56(+), CD244(+)CD3(-)CD56(+), and CD244(+)CD3(+)CD56(+)cells were high, whereas the percentages of NKG2D(+)CD3(-)CD56(+) and NKG2D(+)CD3(+)CD56(+)cells were low in both patient groups. The percentages of NKp44(+)CD3(-)CD56(+) cells were high in both patient groups, whereas the percentages of NKp44(+)CD3(+)CD56(+) cells were higher in the acute group than in convalescent and control groups. The percentages of NKp46(+)CD3(-)CD56(+) cells were high in both patient groups. Higher percentages of perforin(+)CD3(-)CD56(+) and perforin(+)CD3(+)CD56(+) cells were observed in acute and convalescent patients, respectively. Higher cytotoxic activity was observed in acute patients than in controls. IFN-γ expression on NK cells of convalescent patients and on NKT-like cells of both patient groups was indicative of the regulatory role of NK and NKT-like cells. Collectively, these data showed that higher expression of activating receptors on NK/NKT-like cells and perforin(+) NK cells in acute patients could be responsible for increased cytotoxicity. The observed expression of perforin(+) NK cells in the acute phase and IFN-γ(+) NKT-like cells in the subsequent convalescent stage showed that NK/NKT-like cells mount an early and efficient response to chikungunya virus. Further study of the molecular mechanisms that limit viral dissemination/establishment of chronic disease will aid in understanding how NK/NKT-like cells control chikungunya infection.

  7. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  8. Defining the stenotic post-laryngectomy tracheostoma and its impact on the quality of life in laryngectomees: development and validation of a stoma function questionnaire.

    Science.gov (United States)

    Paleri, V; Wight, R G; Owen, S; Hurren, A; Stafford, F W

    2006-10-01

    The aims of this study were to identify if: (i) size of stoma contributes to quality of life (QoL) in laryngectomees; (ii) stoma size has an impact on routine stoma care and function; and (iii) an optimal stoma size exists below which patients experience stoma problems. Cross-sectional study of laryngectomees. Two tertiary care centres. Fifty-seven patients who had undergone total laryngectomy one to five years ago and using tracheo-oesophageal speech as their primary communication means. Three main measures were studied: 1 a new study specific questionnaire designed to assess problems with function and care of the end tracheosto- ma; 2 QoL as assessed by the head and neck QoL instrument; 3 a precision custom designed sizer to measure the minimum stoma diameter. The final study-specific questionnaire contained four items assessing different aspects of stomal function. From raw total scores an overall stomal score was generated. The stoma score was moderately correlated to emotion and speech domains in head and neck Quality of Life questionnaire, indicating that different concepts were being measured. The mean minimum stoma diameter was 15.9 +/- 2.9 mm. There was a significant increase in the area under the receiver operating characteristic curve beyond a threshold value of > or 15 mm; smaller sizes were associated with a poorer stoma score (Mann-Whitney test, P stoma sizer use distressing. Size of stoma significantly contributes to QoL in laryngectomees and stomas with minimum diameters of 14 mm or less are associated with adverse effects on routine stoma function. The study-specific stoma function questionnaire appears to be a useful instrument.

  9. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials.

    Science.gov (United States)

    Ricotti, Valeria; Evans, Matthew R B; Sinclair, Christopher D J; Butler, Jordan W; Ridout, Deborah A; Hogrel, Jean-Yves; Emira, Ahmed; Morrow, Jasper M; Reilly, Mary M; Hanna, Michael G; Janiczek, Robert L; Matthews, Paul M; Yousry, Tarek A; Muntoni, Francesco; Thornton, John S

    2016-01-01

    A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (pmuscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

  10. Experimental study of the leakage rate through cracked reinforced concrete wall elements for defining the functional failure criteria of containment buildings

    International Nuclear Information System (INIS)

    Choun, Young Sun; Cho, Nam So

    2004-01-01

    Containment buildings in nuclear power plants should maintain their structural safety as well as their functional integrity during an operation period. To maintain the functional integrity, the wall and dome of the containment buildings have to maintain their air tightness under extreme loading conditions such as earthquakes, missile impact, and severe accidents. For evaluating the functional failure of containments, it is important to predict the leak amount through cracked concrete walls. The leakage through concrete cracks has been studied since 1972. Buss examined the flow rate of air through a pre-existing crack in a slab under air pressure. Rizkalla el al. initiated an experimental study for the leakage of prestressed concrete building segments under uniaxial and biaxial loadings to simulate the loading condition of containment buildings under an internal pressure. Recently, Salmon el al. initiated an experimental program for determining the leak rates in typical reinforced concrete shear walls subjected to beyond design basis earthquakes. This study investigates the cracking behavior of reinforced concrete containment wall elements under a uniaxial tension and addresses the outline of the leakage test for unlined containment wall elements

  11. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Valeria Ricotti

    Full Text Available A number of promising experimental therapies for Duchenne muscular dystrophy (DMD are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function.15 non-ambulant DMD boys (mean age 13.3 y and 10 age-gender matched healthy controls (mean age 14.6 y were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.. Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation.Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001. A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7, accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9 and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8.These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

  12. Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study.

    Science.gov (United States)

    Tiffany Win, Theingi; Ambale Venkatesh, Bharath; Volpe, Gustavo J; Mewton, Nathan; Rizzi, Patricia; Sharma, Ravi K; Strauss, David G; Lima, Joao A; Tereshchenko, Larisa G

    2015-01-01

    Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance, and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2- and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-wave-duration, PR interval, and P-wave axis were automatically measured using 12 SLTM algorithm. PTFV1 was calculated as a product of PPaV1 and PPdV1. In linear regression after adjustment for demographic characteristics, body mass index, maximum LA volume index, presence of scar, and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76 mV*ms increase in negative abnormal PTFV1 (95% confidence interval [CI] -1.42 to -0.09; P = .025), 15.3 ms prolongation of PPdV1 (95% CI 6.9 to 23.8; P = .001) and 5.4 ms prolongation of averaged P-duration (95% CI 0.9-10.0; P = .020). LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes and decrease in LA emptying fraction and LA reservoir function. LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1, and P-duration, but does not affect LA function. Copyright © 2015 Heart Rhythm Society. All rights reserved.

  13. Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.

    Directory of Open Access Journals (Sweden)

    Jason Abernathy

    Full Text Available Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.

  14. Two functional motifs define the interaction, internalization and toxicity of the cell-penetrating antifungal peptide PAF26 on fungal cells.

    Directory of Open Access Journals (Sweden)

    Alberto Muñoz

    Full Text Available The synthetic, cell penetrating hexapeptide PAF26 (RKKWFW is antifungal at low micromolar concentrations and has been proposed as a model for cationic, cell-penetrating antifungal peptides. Its short amino acid sequence facilitates the analysis of its structure-activity relationships using the fungal models Neurospora crassa and Saccharomyces cerevisiae, and human and plant pathogens Aspergillus fumigatus and Penicillium digitatum, respectively. Previously, PAF26 at low fungicidal concentrations was shown to be endocytically internalized, accumulated in vacuoles and then actively transported into the cytoplasm where it exerts its antifungal activity. In the present study, two PAF26 derivatives, PAF95 (AAAWFW and PAF96 (RKKAAA, were designed to characterize the roles of the N-terminal cationic and the C-terminal hydrophobic motifs in PAF26's mode-of-action. PAF95 and PAF96 exhibited substantially reduced antifungal activity against all the fungi analyzed. PAF96 localized to fungal cell envelopes and was not internalized by the fungi. In contrast, PAF95 was taken up into vacuoles of N. crassa, wherein it accumulated and was trapped without toxic effects. Also, the PAF26 resistant Δarg1 strain of S. cerevisiae exhibited increased PAF26 accumulation in vacuoles. Live-cell imaging of GFP-labelled nuclei in A. fumigatus showed that transport of PAF26 from the vacuole to the cytoplasm was followed by nuclear breakdown and dissolution. This work demonstrates that the amphipathic PAF26 possesses two distinct motifs that allow three stages in its antifungal action to be defined: (i its interaction with the cell envelope; (ii its internalization and transport to vacuoles mediated by the aromatic hydrophobic domain; and (iii its transport from vacuoles to the cytoplasm. Significantly, cationic residues in PAF26 are important not only for the electrostatic attraction and interaction with the fungal cell but also for transport from the vacuole to the

  15. Can play be defined?

    DEFF Research Database (Denmark)

    Eichberg, Henning

    2015-01-01

    Can play be defined? There is reason to raise critical questions about the established academic demand that at phenomenon – also in humanist studies – should first of all be defined, i.e. de-lineated and by neat lines limited to a “little box” that can be handled. The following chapter develops....... Human beings can very well understand play – or whatever phenomenon in human life – without defining it....

  16. Symbiotic specificity, association patterns, and function determine community responses to global changes: defining critical research areas for coral-Symbiodinium symbioses.

    Science.gov (United States)

    Fabina, Nicholas S; Putnam, Hollie M; Franklin, Erik C; Stat, Michael; Gates, Ruth D

    2013-11-01

    Climate change-driven stressors threaten the persistence of coral reefs worldwide. Symbiotic relationships between scleractinian corals and photosynthetic endosymbionts (genus Symbiodinium) are the foundation of reef ecosystems, and these associations are differentially impacted by stress. Here, we couple empirical data from the coral reefs of Moorea, French Polynesia, and a network theoretic modeling approach to evaluate how patterns in coral-Symbiodinium associations influence community stability under climate change. To introduce the effect of climate perturbations, we simulate local 'extinctions' that represent either the loss of coral species or the ability to engage in symbiotic interactions. Community stability is measured by determining the duration and number of species that persist through the simulated extinctions. Our results suggest that four factors greatly increase coral-Symbiodinium community stability in response to global changes: (i) the survival of generalist hosts and symbionts maximizes potential symbiotic unions; (ii) elevated symbiont diversity provides redundant or complementary symbiotic functions; (iii) compatible symbiotic assemblages create the potential for local recolonization; and (iv) the persistence of certain traits associate with symbiotic diversity and redundancy. Symbiodinium may facilitate coral persistence through novel environmental regimes, but this capacity is mediated by symbiotic specificity, association patterns, and the functional performance of the symbionts. Our model-based approach identifies general trends and testable hypotheses in coral-Symbiodinium community responses. Future studies should consider similar methods when community size and/or environmental complexity preclude experimental approaches. © 2013 John Wiley & Sons Ltd.

  17. Cerebral blood flow with [15O]water PET studies using an image-derived input function and MR-defined carotid centerlines

    Science.gov (United States)

    Fung, Edward K.; Carson, Richard E.

    2013-03-01

    Full quantitative analysis of brain PET data requires knowledge of the arterial input function into the brain. Such data are normally acquired by arterial sampling with corrections for delay and dispersion to account for the distant sampling site. Several attempts have been made to extract an image-derived input function (IDIF) directly from the internal carotid arteries that supply the brain and are often visible in brain PET images. We have devised a method of delineating the internal carotids in co-registered magnetic resonance (MR) images using the level-set method and applying the segmentations to PET images using a novel centerline approach. Centerlines of the segmented carotids were modeled as cubic splines and re-registered in PET images summed over the early portion of the scan. Using information from the anatomical center of the vessel should minimize partial volume and spillover effects. Centerline time-activity curves were taken as the mean of the values for points along the centerline interpolated from neighboring voxels. A scale factor correction was derived from calculation of cerebral blood flow (CBF) using gold standard arterial blood measurements. We have applied the method to human subject data from multiple injections of [15O]water on the HRRT. The method was assessed by calculating the area under the curve (AUC) of the IDIF and the CBF, and comparing these to values computed using the gold standard arterial input curve. The average ratio of IDIF to arterial AUC (apparent recovery coefficient: aRC) across 9 subjects with multiple (n = 69) injections was 0.49 ± 0.09 at 0-30 s post tracer arrival, 0.45 ± 0.09 at 30-60 s, and 0.46 ± 0.09 at 60-90 s. Gray and white matter CBF values were 61.4 ± 11.0 and 15.6 ± 3.0 mL/min/100 g tissue using sampled blood data. Using IDIF centerlines scaled by the average aRC over each subjects’ injections, gray and white matter CBF values were 61.3 ± 13.5 and 15.5 ± 3.4 mL/min/100 g tissue. Using global

  18. Towards the Development of Clinical Measures for Spinal Cord Injury Based on the International Classification of Functioning, Disability and Health With Rasch Analyses

    DEFF Research Database (Denmark)

    Ballert, Carolina S; Stucki, Gerold; Biering-Sørensen, Fin

    2014-01-01

    item dependency was observed between ICF categories of the same chapters. Group effects for age and sex were observed only to a small extent. CONCLUSIONS: The validity of ICF categories to develop measures of functioning in SCI for clinical practice and research is to some extent supported. Model......OBJECTIVES: To determine whether the International Classification of Functioning, Disability and Health (ICF) categories relevant to spinal cord injury (SCI) can be integrated in clinical measures and to obtain insights to guide their future operationalization. Specific aims are to find out whether...... in specialized centers within 15 countries from 2006 through 2008. SETTING: Secondary data analysis. PARTICIPANTS: Adults (N=1048) with SCI from the early postacute and long-term living context. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Two unidimensional Rasch analyses: one for the ICF categories...

  19. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

  20. Nanostructured self-assembling peptides as a defined extracellular matrix for long-term functional maintenance of primary hepatocytes in a bioartificial liver modular device

    Directory of Open Access Journals (Sweden)

    Giri S

    2013-04-01

    Full Text Available Shibashish Giri,1 Ulf-Dietrich Braumann,2,3 Priya Giri,1,3 Ali Acikgöz,1,4 Patrick Scheibe,3,5 Karen Nieber,6 Augustinus Bader1 1Department of Cell Techniques and Applied Stem Cell Biology, Center for Biotechnology and Biomedicine (BBZ, 2Institute for Medical Informatics, Statistics, and Epidemiology (IMISE, University of Leipzig, Leipzig, Germany; 3Interdisciplinary Center for Bioinformatics (IZBI, University of Leipzig, Leipzig, Germany; 4Klinikum St Georg, Leipzig, Germany; 5Translational Center for Regenerative Medicine (TRM Leipzig, 6Department of Pharmacology for Natural Sciences, Institute of Pharmacy, University of Leipzig, Leipzig, Germany Abstract: Much effort has been directed towards the optimization of the capture of in vivo hepatocytes from their microenvironment. Some methods of capture include an ex vivo cellular model in a bioreactor based liver module, a micropatterned module, a microfluidic 3D chip, coated plates, and other innovative approaches for the functional maintenance of primary hepatocytes. However, none of the above methods meet US Food and Drug Administration (FDA guidelines, which recommend and encourage that the duration of a toxicity assay of a drug should be a minimum of 14 days, to a maximum of 90 days for a general toxicity assay. Existing innovative reports have used undefined extracellular matrices like matrigel, rigid collagen, or serum supplementations, which are often problematic, unacceptable in preclinical and clinical applications, and can even interfere with experimental outcomes. We have overcome these challenges by using integrated nanostructured self-assembling peptides and a special combination of growth factors and cytokines to establish a proof of concept to mimic the in vivo hepatocyte microenvironment pattern in vitro for predicting the in vivo drug hepatotoxicity in a scalable bioartificial liver module. Hepatocyte functionality (albumin, urea was measured at days 10, 30, 60, and 90 and we

  1. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  2. Burn patients' return to daily activities and participation as defined by the International Classification of Functioning, Disability and Health: A systematic review.

    Science.gov (United States)

    Osborne, Candice L; Meyer, Walter J; Ottenbacher, Kenneth J; Arcari, Christine M

    2017-06-01

    The World Health Organization's International Classification of Functioning, Disability and Health (ICF) is a universal classification system of health and health-related domains. The ICF has been successfully applied to a wide range of health conditions and diseases; however, its application in the field of burn recovery has been minimal. This systematic review uses the domains of the ICF component 'activities and participation' to explore: (1) the extent to which return to daily activities and community participation after burn has been examined in the pediatric population, (2) the most common assessments used to determine activity and participation outcomes, and (3) what activity and participation areas are most affected in the pediatric burn population after discharge from acute care. Results determined that it is difficult to draw overarching conclusions in the area of return to 'activities and participation' for children with burn based on the paucity of current evidence. Of the studies conducted, few examined the same subtopics or used similar measurements. This suggests a need for more robust studies in this area in order to inform and improve burn rehabilitation practices to meet the potential needs of burn patients beyond an acute care setting. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  3. Towards the development of clinical measures for spinal cord injury based on the International Classification of Functioning, Disability and Health with Rasch analyses.

    Science.gov (United States)

    Ballert, Carolina S; Stucki, Gerold; Biering-Sørensen, Fin; Cieza, Alarcos

    2014-09-01

    To determine whether the International Classification of Functioning, Disability and Health (ICF) categories relevant to spinal cord injury (SCI) can be integrated in clinical measures and to obtain insights to guide their future operationalization. Specific aims are to find out whether the ICF categories relevant to SCI fit a Rasch model taking into consideration the dimensionality found in previous investigations, local item dependencies, or differential item functioning. All second-level ICF categories collected in the Development of ICF Core Sets for SCI project in specialized centers within 15 countries from 2006 through 2008. Secondary data analysis. Adults (N=1048) with SCI from the early postacute and long-term living context. Not applicable. Two unidimensional Rasch analyses: one for the ICF categories from body functions and body structures components and another for the ICF categories from the activities and participation component. Results support good reliability and targeting of the ICF categories in both dimensions. In each dimension, few ICF categories were subject to misfit. Local item dependency was observed between ICF categories of the same chapters. Group effects for age and sex were observed only to a small extent. The validity of ICF categories to develop measures of functioning in SCI for clinical practice and research is to some extent supported. Model adjustments were suggested to further improve their operationalization and psychometrics. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. Niemann-Pick C1 (NPC1/NPC1-like1 Chimeras Define Sequences Critical for NPC1’s Function as a Filovirus Entry Receptor

    Directory of Open Access Journals (Sweden)

    Esther Ndungo

    2012-10-01

    Full Text Available We recently demonstrated that Niemann-Pick C1 (NPC1, a ubiquitous 13-pass cellular membrane protein involved in lysosomal cholesterol transport, is a critical entry receptor for filoviruses. Here we show that Niemann-Pick C1-like1 (NPC1L1, an NPC1 paralog and hepatitis C virus entry factor, lacks filovirus receptor activity. We exploited the structural similarity between NPC1 and NPC1L1 to construct and analyze a panel of chimeras in which NPC1L1 sequences were replaced with cognate sequences from NPC1. Only one chimera, NPC1L1 containing the second luminal domain (C of NPC1 in place of its own, bound to the viral glycoprotein, GP. This engineered protein mediated authentic filovirus infection nearly as well as wild-type NPC1, and more efficiently than did a minimal NPC1 domain C-based receptor recently described by us. A reciprocal chimera, NPC1 containing NPC1L1’s domain C, was completely inactive. Remarkably, an intra-domain NPC1L1-NPC1 chimera bearing only a ~130-amino acid N–terminal region of NPC1 domain C could confer substantial viral receptor activity on NPC1L1. Taken together, these findings account for the failure of NPC1L1 to serve as a filovirus receptor, highlight the central role of the luminal domain C of NPC1 in filovirus entry, and reveal the direct involvement of N–terminal domain C sequences in NPC1’s function as a filovirus receptor.

  5. Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells.

    Science.gov (United States)

    Velu, Vijayakumar; Mylvaganam, Geetha Hanna; Gangadhara, Sailaja; Hong, Jung Joo; Iyer, Smita S; Gumber, Sanjeev; Ibegbu, Chris C; Villinger, Francois; Amara, Rama Rao

    2016-09-01

    Chronic HIV infection is associated with accumulation of germinal center (GC) T follicular helper (Tfh) cells in the lymphoid tissue. The GC Tfh cells can be heterogeneous based on the expression of chemokine receptors associated with T helper lineages, such as CXCR3 (Th1), CCR4 (Th2), and CCR6 (Th17). However, the heterogeneous nature of GC Tfh cells in the lymphoid tissue and its association with viral persistence and Ab production during chronic SIV/HIV infection are not known. To address this, we characterized the expression of CXCR3, CCR4, and CCR6 on GC Tfh cells in lymph nodes following SIVmac251 infection in rhesus macaques. In SIV-naive rhesus macaques, only a small fraction of GC Tfh cells expressed CXCR3, CCR4, and CCR6. However, during chronic SIV infection, the majority of GC Tfh cells expressed CXCR3, whereas the proportion of CCR4(+) cells did not change, and CCR6(+) cells decreased. CXCR3(+), but not CXCR3(-), GC Tfh cells produced IFN-γ (Th1 cytokine) and IL-21 (Tfh cytokine), whereas both subsets expressed CD40L following stimulation. Immunohistochemistry analysis demonstrated an accumulation of CD4(+)IFN-γ(+) T cells within the hyperplastic follicles during chronic SIV infection. CXCR3(+) GC Tfh cells also expressed higher levels of ICOS, CCR5, and α4β7 and contained more copies of SIV DNA compared with CXCR3(-) GC Tfh cells. However, CXCR3(+) and CXCR3(-) GC Tfh cells delivered help to B cells in vitro for production of IgG. These data demonstrate that chronic SIV infection promotes expansion of Th1-biased GC Tfh cells, which are phenotypically and functionally distinct from conventional GC Tfh cells and contribute to hypergammaglobulinemia and viral reservoirs. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.

    Science.gov (United States)

    Zhang, Hong-Zhe; Kim, Moo Hyun; Han, Jin-Yeong; Jeong, Young-Hoon

    2014-01-01

    Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN>242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA (r=0.56), with moderate agreement (κ=0.46 and κ=0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r=0.42) and agreement (κ=0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.

  7. Functional and gene network analyses of transcriptional signatures characterizing pre-weaned bovine mammary parenchyma or fat pad uncovered novel inter-tissue signaling networks during development

    Directory of Open Access Journals (Sweden)

    Lewin Harris A

    2010-05-01

    Full Text Available Abstract Background The neonatal bovine mammary fat pad (MFP surrounding the mammary parenchyma (PAR is thought to exert proliferative effects on the PAR through secretion of local modulators of growth induced by systemic hormones. We used bioinformatics to characterize transcriptomics differences between PAR and MFP from ~65 d old Holstein heifers. Data were mined to uncover potential crosstalk through the analyses of signaling molecules preferentially expressed in one tissue relative to the other. Results Over 9,000 differentially expressed genes (DEG; False discovery rate ≤ 0.05 were found of which 1,478 had a ≥1.5-fold difference between PAR and MFP. Within the DEG highly-expressed in PAR vs. MFP (n = 736 we noted significant enrichment of functions related to cell cycle, structural organization, signaling, and DNA/RNA metabolism. Only actin cytoskeletal signaling was significant among canonical pathways. DEG more highly-expressed in MFP vs. PAR (n = 742 belong to lipid metabolism, signaling, cell movement, and immune-related functions. Canonical pathways associated with metabolism and signaling, particularly immune- and metabolism-related were significantly-enriched. Network analysis uncovered a central role of MYC, TP53, and CTNNB1 in controlling expression of DEG highly-expressed in PAR vs. MFP. Similar analysis suggested a central role for PPARG, KLF2, EGR2, and EPAS1 in regulating expression of more highly-expressed DEG in MFP vs. PAR. Gene network analyses revealed putative inter-tissue crosstalk between cytokines and growth factors preferentially expressed in one tissue (e.g., ANGPTL1, SPP1, IL1B in PAR vs. MFP; ADIPOQ, IL13, FGF2, LEP in MFP vs. PAR with DEG preferentially expressed in the other tissue, particularly transcription factors or pathways (e.g., MYC, TP53, and actin cytoskeletal signaling in PAR vs. MFP; PPARG and LXR/RXR Signaling in MFP vs. PAR. Conclusions Functional analyses underscored a reciprocal influence in

  8. Defining Overweight and Obesity

    Science.gov (United States)

    ... Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and Obesity Recommend on Facebook Tweet Share Compartir ... weight for a given height is described as overweight or obese. Body Mass Index, or BMI, is ...

  9. Drinking Levels Defined

    Science.gov (United States)

    ... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... Definition of Drinking at Low Risk for Developing Alcohol Use Disorder (AUD): For women, low-risk drinking is defined ...

  10. Defining and Selecting Independent Directors

    Directory of Open Access Journals (Sweden)

    Eric Pichet

    2017-10-01

    Full Text Available Drawing from the Enlightened Shareholder Theory that the author first developed in 2011, this theoretical paper with practical and normative ambitions achieves a better definition of independent director, while improving the understanding of the roles he fulfils on boards of directors. The first part defines constructs like firms, Governance system and Corporate governance, offering a clear distinction between the latter two concepts before explaining the four main missions of a board. The second part defines the ideal independent director by outlining the objective qualities that are necessary and adding those subjective aspects that have turned this into a veritable profession. The third part defines the ideal process for selecting independent directors, based on nominating committees that should themselves be independent. It also includes ways of assessing directors who are currently in function, as well as modalities for renewing their mandates. The paper’s conclusion presents the Paradox of the Independent Director.

  11. Defining Documentary Film

    DEFF Research Database (Denmark)

    Juel, Henrik

    2006-01-01

    A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film......A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film...

  12. Gene Expression Responses to FUS, EWS, and TAF15 Reduction and Stress Granule Sequestration Analyses Identifies FET-Protein Non-Redundant Functions

    DEFF Research Database (Denmark)

    Blechingberg, Jenny; Luo, Yonglun; Bolund, Lars

    2012-01-01

    The FET family of proteins is composed of FUS/TLS, EWS/EWSR1, and TAF15 and possesses RNA- and DNA-binding capacities. The FET-proteins are involved in transcriptional regulation and RNA processing, and FET-gene deregulation is associated with development of cancer and protein granule formations...... in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and trinucleotide repeat expansion diseases. We here describe a comparative characterization of FET-protein localization and gene regulatory functions. We show that FUS and TAF15 locate to cellular stress granules to a larger extend than EWS....... FET-proteins have no major importance for stress granule formation and cellular stress responses, indicating that FET-protein stress granule association most likely is a downstream response to cellular stress. Gene expression analyses showed that the cellular response towards FUS and TAF15 reduction...

  13. Definably compact groups definable in real closed fields. I

    OpenAIRE

    Barriga, Eliana

    2017-01-01

    We study definably compact definably connected groups definable in a sufficiently saturated real closed field $R$. We introduce the notion of group-generic point for $\\bigvee$-definable groups and show the existence of group-generic points for definably compact groups definable in a sufficiently saturated o-minimal expansion of a real closed field. We use this notion along with some properties of generic sets to prove that for every definably compact definably connected group $G$ definable in...

  14. Academic and Social Functioning Associated with Attention-Deficit/Hyperactivity Disorder: Latent Class Analyses of Trajectories from Kindergarten to Fifth Grade.

    Science.gov (United States)

    DuPaul, George J; Morgan, Paul L; Farkas, George; Hillemeier, Marianne M; Maczuga, Steve

    2016-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) are known to exhibit significantly lower academic and social functioning than other children. Yet the field currently lacks knowledge about specific impairment trajectories experienced by children with ADHD, which may constrain early screening and intervention effectiveness. Data were analyzed from a nationally representative U.S. cohort in the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K) for 590 children (72.7 % male) whose parents reported a formal diagnosis of ADHD. Children's math, reading, and interpersonal skills were assessed at 5 time points between kindergarten and fifth grade. Growth mixture model analyses indicated 4 latent trajectory classes for reading, 8 classes for math, and 4 classes for interpersonal skills. Membership in reading and math trajectory classes was strongly related; overlaps with interpersonal skills classes were weaker. Trajectory class membership was correlated with demographic characteristics and behavioral functioning. Children with ADHD display substantial heterogeneity in their reading, math, and interpersonal growth trajectories, with some groups of children especially likely to display relatively severe levels of academic and social impairment over time. Early screening and intervention to address impairment, particularly reading difficulties, among kindergarten students with ADHD is warranted.

  15. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation. Functional modules F9--F16 -- Volume 2, Part 2, Revision 4

    Energy Technology Data Exchange (ETDEWEB)

    West, J.T.; Hoffman, T.J.; Emmett, M.B.; Childs, K.W.; Petrie, L.M.; Landers, N.F.; Bryan, C.B.; Giles, G.E. [Oak Ridge National Lab., TN (United States)

    1995-04-01

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automate the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system has been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.2 of the system. The manual is divided into three volumes: Volume 1--for the control module documentation, Volume 2--for functional module documentation; and Volume 3--for documentation of the data libraries and subroutine libraries. This volume discusses the following functional modules: MORSE-SGC; HEATING 7.2; KENO V.a; JUNEBUG-II; HEATPLOT-S; REGPLOT 6; PLORIGEN; and OCULAR.

  16. Loss-of-function analyses of the fragile X-related and dopamine receptor genes by RNA interference in the cricket Gryllus bimaculatus.

    Science.gov (United States)

    Hamada, Aska; Miyawaki, Katsuyuki; Honda-sumi, Eri; Tomioka, Kenji; Mito, Taro; Ohuchi, Hideyo; Noji, Sumihare

    2009-08-01

    In order to explore a possibility that the cricket Gryllus bimaculatus would be a useful model to unveil molecular mechanisms of human diseases, we performed loss-of-function analyses of Gryllus genes homologous to human genes that are responsible for human disorders, fragile X mental retardation 1 (fmr1) and Dopamine receptor (DopR). We cloned cDNAs of their Gryllus homologues, Gb'fmr1, Gb'DopRI, and Gb'DopRII, and analyzed their functions with use of nymphal RNA interference (RNAi). For Gb'fmr1, three major phenotypes were observed: (1) abnormal wing postures, (2) abnormal calling song, and (3) loss of the circadian locomotor rhythm, while for Gb'DopRI, defects of wing posture and morphology were found. These results indicate that the cricket has the potential to become a novel model system to explore human neuronal pathogenic mechanisms and to screen therapeutic drugs by RNAi. Copyright (c) 2009 Wiley-Liss, Inc.

  17. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation. Functional modules F9--F16 -- Volume 2, Part 2, Revision 4

    International Nuclear Information System (INIS)

    West, J.T.; Hoffman, T.J.; Emmett, M.B.; Childs, K.W.; Petrie, L.M.; Landers, N.F.; Bryan, C.B.; Giles, G.E.

    1995-04-01

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automate the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system has been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.2 of the system. The manual is divided into three volumes: Volume 1--for the control module documentation, Volume 2--for functional module documentation; and Volume 3--for documentation of the data libraries and subroutine libraries. This volume discusses the following functional modules: MORSE-SGC; HEATING 7.2; KENO V.a; JUNEBUG-II; HEATPLOT-S; REGPLOT 6; PLORIGEN; and OCULAR

  18. Defining Game Mechanics

    DEFF Research Database (Denmark)

    Sicart (Vila), Miguel Angel

    2008-01-01

    This article defins game mechanics in relation to rules and challenges. Game mechanics are methods invoked by agents for interacting with the game world. I apply this definition to a comparative analysis of the games Rez, Every Extend Extra and Shadow of the Colossus that will show the relevance...... of a formal definition of game mechanics. Udgivelsesdato: Dec 2008...

  19. Modal Logics and Definability

    OpenAIRE

    Kuusisto, Antti

    2013-01-01

    In recent years, research into the mathematical foundations of modal logic has become increasingly popular. One of the main reasons for this is the fact that modal logic seems to adapt well to the requirements of a wide range of different fields of application. This paper is a summary of some of the author’s contributions to the understanding of modal definability theory.

  20. Defining Abnormally Low Tenders

    DEFF Research Database (Denmark)

    Ølykke, Grith Skovgaard; Nyström, Johan

    2017-01-01

    The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

  1. Software Defined Coded Networking

    DEFF Research Database (Denmark)

    Di Paola, Carla; Roetter, Daniel Enrique Lucani; Palazzo, Sergio

    2017-01-01

    the quality of each link and even across neighbouring links and using simulations to show that an additional reduction of packet transmission in the order of 40% is possible. Second, to advocate for the use of network coding (NC) jointly with software defined networking (SDN) providing an implementation...

  2. Defining depth of anesthesia.

    Science.gov (United States)

    Shafer, S L; Stanski, D R

    2008-01-01

    In this chapter, drawn largely from the synthesis of material that we first presented in the sixth edition of Miller's Anesthesia, Chap 31 (Stanski and Shafer 2005; used by permission of the publisher), we have defined anesthetic depth as the probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of non-responsiveness at defined effect site concentrations. This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. The "clinical art" of anesthesia requires calibration of these observations of stimuli and responses (verbal responses, movement, tachycardia) against the dose and concentration of anesthetic drugs used to reduce the probability of response, constantly adjusting the administered dose to achieve the desired anesthetic depth. In our definition of "depth of anesthesia" we define the need for two components to create the anesthetic state: hypnosis created with drugs such as propofol or the inhalational anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness.

  3. Defining and classifying syncope

    NARCIS (Netherlands)

    Thijs, Roland D.; Wieling, Wouter; Kaufmann, Horacio; van Dijk, Gert

    2004-01-01

    There is no widely adopted definition or classification of syncope and related disorders. This lack of uniformity harms patient care, research, and medical education. In this article, syncope is defined as a form of transient loss of consciousness (TLOC) due to cerebral hypoperfusion. Differences

  4. Human chimera-type galectin-3: defining the critical tail length for high-affinity glycoprotein/cell surface binding and functional competition with galectin-1 in neuroblastoma cell growth regulation.

    Science.gov (United States)

    Kopitz, Jürgen; Vértesy, Sabine; André, Sabine; Fiedler, Sabine; Schnölzer, Martina; Gabius, Hans-Joachim

    2014-09-01

    Many human proteins have a modular design with receptor and structural domains. Using adhesion/growth-regulatory galectin-3 as model, we describe an interdisciplinary strategy to define the functional significance of its tail established by nine non-triple helical collagen-like repeats (I-IX) and the N-terminal peptide. Genetic engineering with sophisticated mass spectrometric product analysis provided the tools for biotesting, i.e. eight protein variants with different degrees of tail truncation. Evidently,various aspects of galectin-3 activity (cis binding and cell bridging) are affected by tail shortening in a different manner. Thus, this combined approach reveals an unsuspected complexity of structure-function relationship, encouraging further application beyond this chimera-type galectin. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. Defining Legal Moralism

    DEFF Research Database (Denmark)

    Thaysen, Jens Damgaard

    2015-01-01

    This paper discusses how legal moralism should be defined. It is argued that legal moralism should be defined as the position that “For any X, it is always a pro tanto reason for justifiably imposing legal regulation on X that X is morally wrong (where “morally wrong” is not conceptually equivalent...... to “harmful”)”. Furthermore, a distinction between six types of legal moralism is made. The six types are grouped according to whether they are concerned with the enforcement of positive or critical morality, and whether they are concerned with criminalising, legally restricting, or refraining from legally...... protecting morally wrong behaviour. This is interesting because not all types of legal moralism are equally vulnerable to the different critiques of legal moralism that have been put forth. Indeed, I show that some interesting types of legal moralism have not been criticised at all....

  6. Definable davies' theorem

    DEFF Research Database (Denmark)

    Törnquist, Asger Dag; Weiss, W.

    2009-01-01

    We prove the following descriptive set-theoretic analogue of a theorem of R. 0. Davies: Every σ function f:ℝ × ℝ → ℝ can be represented as a sum of rectangular Σ functions if and only if all reals are constructible.......We prove the following descriptive set-theoretic analogue of a theorem of R. 0. Davies: Every σ function f:ℝ × ℝ → ℝ can be represented as a sum of rectangular Σ functions if and only if all reals are constructible....

  7. Defining local food

    DEFF Research Database (Denmark)

    Eriksen, Safania Normann

    2013-01-01

    Despite evolving local food research, there is no consistent definition of “local food.” Various understandings are utilized, which have resulted in a diverse landscape of meaning. The main purpose of this paper is to examine how researchers within the local food systems literature define local...... food, and how these definitions can be used as a starting point to identify a new taxonomy of local food based on three domains of proximity....

  8. Genome-wide analyses and functional classification of proline repeat-rich proteins: potential role of eIF5A in eukaryotic evolution.

    Directory of Open Access Journals (Sweden)

    Ajeet Mandal

    Full Text Available The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro and/or PPG (Pro-Pro-Gly-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids, only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution.

  9. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation. Functional modules F1--F8 -- Volume 2, Part 1, Revision 4

    International Nuclear Information System (INIS)

    Greene, N.M.; Petrie, L.M.; Westfall, R.M.; Bucholz, J.A.; Hermann, O.W.; Fraley, S.K.

    1995-04-01

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automate the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system has been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.2 of the system. The manual is divided into three volumes: Volume 1--for the control module documentation; Volume 2--for functional module documentation; and Volume 3--for documentation of the data libraries and subroutine libraries

  10. SCALE: A modular code system for performing standardized computer analyses for licensing evaluation. Functional modules F1--F8 -- Volume 2, Part 1, Revision 4

    Energy Technology Data Exchange (ETDEWEB)

    Greene, N.M.; Petrie, L.M.; Westfall, R.M.; Bucholz, J.A.; Hermann, O.W.; Fraley, S.K. [Oak Ridge National Lab., TN (United States)

    1995-04-01

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automate the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system has been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.2 of the system. The manual is divided into three volumes: Volume 1--for the control module documentation; Volume 2--for functional module documentation; and Volume 3--for documentation of the data libraries and subroutine libraries.

  11. Principal component and discriminant analyses as powerful tools to support taxonomic identification and their use for functional and phylogenetic signal detection of isolated fossil shark teeth.

    Directory of Open Access Journals (Sweden)

    Giuseppe Marramà

    Full Text Available Identifying isolated teeth of fossil selachians only based on qualitative characters is sometimes hindered by similarity in their morphology, resulting often in heated taxonomic debates. On the other hand, the use of quantitative characters (i.e. measurements has been often neglected or underestimated in characterization and identification of fossil teeth of selachians. Here we show that, employing a robust methodological protocol based on principal component and discriminant analyses on a sample of 175 isolated fossil teeth of lamniform sharks, the traditional morphometrics can be useful to support and complement the classic taxonomic identification made on qualitative features. Furthermore, we show that discriminant analysis can be successfully useful to assign indeterminate isolated shark teeth to a certain taxon. Finally, the degree of separation of the clusters might be used to predict functional and probably also phylogenetic signals in lamniform shark teeth. However, this needs to be tested in the future employing teeth of more extant and extinct lamniform sharks and it must be pointed out that this approach does not replace in any way the qualitative analysis, but it is intended to complement and support it.

  12. Morphological and functional analyses of skeletal muscles from an immunodeficient animal model of limb-girdle muscular dystrophy type 2E.

    Science.gov (United States)

    Giovannelli, Gaia; Giacomazzi, Giorgia; Grosemans, Hanne; Sampaolesi, Maurilio

    2018-02-24

    Limb-girdle muscular dystrophy type 2E (LGMD2E) is caused by mutations in the β-sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscles. β-Sarcoglycan-deficient (Sgcb-null) mice develop severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. In this study we performed morphological (histological and cellular characterization) and functional (isometric tetanic force and fatigue) analyses in dystrophic mice. Comparison studies were carried out in 1-month-old (clinical onset of the disease) and 7-month-old control mice (C57Bl/6J, Rag2/γc-null) and immunocompetent and immunodeficient dystrophic mice (Sgcb-null and Sgcb/Rag2/γc-null, respectively). We found that the lack of an immunological system resulted in an increase of calcification in striated muscles without impairing extensor digitorum longus muscle performance. Sgcb/Rag2/γc-null muscles showed a significant reduction of alkaline phosphate-positive mesoangioblasts. The immunological system counteracts skeletal muscle degeneration in the murine model of LGMD2E. Muscle Nerve, 2018. © 2018 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.

  13. Problems raised by pulse analysers - functional multi-dimensional analysers; Problemes poses par les analyseurs en impulsions - Analyseurs multidimensionnels fonctionnels; Problemy, voznikayushchie v svyazi s ispol'zovaniem analizatorov impul'sov - funktsional'nye mnogorazmernye analizatory; Problemas planteados por los analizadores de impulsos - Analizadores multidimensionales funcionales

    Energy Technology Data Exchange (ETDEWEB)

    Pages, A [Centre d' Etudes Nucleaires de Saclay (France)

    1962-04-15

    Experimenters are making increasingly frequent use of analysis units by which a function of several parameters can be obtained (the number of parameters and the relative precision of each of them being variable from experiment to experiment). Present-day analysers are poorly suited to the steadily growing complexity of experiments. There are several reasons for this: the number of possible parameters is far too small (unblocking only on 100-channel and 256-channel analysers) as is also their capacity; this limitation considerably increases the accelerator time; sometimes the poor ''yield'' of these analysers makes the experiment impossible; moreover, being designed in a single ''block'', they are lacking in flexibility for use. During 1958-59 a multi-dimensional apparatus limited to 2 paths of 63 channels was studied and built. The various essential functions are separated: analysis, transfer (multi-dimensional operation), utilization of results. At the SEG, Messrs. Amram, Guillon and Thenard are designing and building a multidimensional analyser, 1023 channels by 63 channels (for the neutron velocity measurement group of the SPNBE). In order to deal with the above-mentioned limitations, the electronics laboratory of the SPNBE is also developing a functional multi-dimensional analyser, in which the transfer function itself has been broken down into units (interrupter, non-integrator memory, conditioner and computer). Like the limits defining the paths, the types of units selected vary in accordance with the requirements and complexity of the experiment (standard interfunctional language). (author) [French] Les experimentateurs utilisent de plus en plus frequemment des ensembles d'analyse permettant d'obtenir une fonction de plusieurs parametres (le nombre de parametres pouvant varier d'une experience a l'autre ainsi que la precision relative de chacun de ceux-ci). Les analyseurs actuels se pretent mal a la complexite toujours croissante des experiences et ceci pour

  14. Network Coded Software Defined Networking

    DEFF Research Database (Denmark)

    Krigslund, Jeppe; Hansen, Jonas; Roetter, Daniel Enrique Lucani

    2015-01-01

    Software Defined Networking (SDN) and Network Coding (NC) are two key concepts in networking that have garnered a large attention in recent years. On the one hand, SDN's potential to virtualize services in the Internet allows a large flexibility not only for routing data, but also to manage....... This paper advocates for the use of SDN to bring about future Internet and 5G network services by incorporating network coding (NC) functionalities. The inherent flexibility of both SDN and NC provides a fertile ground to envision more efficient, robust, and secure networking designs, that may also...

  15. Network Coded Software Defined Networking

    DEFF Research Database (Denmark)

    Hansen, Jonas; Roetter, Daniel Enrique Lucani; Krigslund, Jeppe

    2015-01-01

    Software defined networking has garnered large attention due to its potential to virtualize services in the Internet, introducing flexibility in the buffering, scheduling, processing, and routing of data in network routers. SDN breaks the deadlock that has kept Internet network protocols stagnant...... for decades, while applications and physical links have evolved. This article advocates for the use of SDN to bring about 5G network services by incorporating network coding (NC) functionalities. The latter constitutes a major leap forward compared to the state-of-the- art store and forward Internet paradigm...

  16. Defined contribution health benefits.

    Science.gov (United States)

    Fronstin, P

    2001-03-01

    This Issue Brief discusses the emerging issue of "defined contribution" (DC) health benefits. The term "defined contribution" is used to describe a wide variety of approaches to the provision of health benefits, all of which have in common a shift in the responsibility for payment and selection of health care services from employers to employees. DC health benefits often are mentioned in the context of enabling employers to control their outlay for health benefits by avoiding increases in health care costs. DC health benefits may also shift responsibility for choosing a health plan and the associated risks of choosing a plan from employers to employees. There are three primary reasons why some employers currently are considering some sort of DC approach. First, they are once again looking for ways to keep their health care cost increases in line with overall inflation. Second, some employers are concerned that the public "backlash" against managed care will result in new legislation, regulations, and litigation that will further increase their health care costs if they do not distance themselves from health care decisions. Third, employers have modified not only most employee benefit plans, but labor market practices in general, by giving workers more choice, control, and flexibility. DC-type health benefits have existed as cafeteria plans since the 1980s. A cafeteria plan gives each employee the opportunity to determine the allocation of his or her total compensation (within employer-defined limits) among various employee benefits (primarily retirement or health). Most types of DC health benefits currently being discussed could be provided within the existing employment-based health insurance system, with or without the use of cafeteria plans. They could also allow employees to purchase health insurance directly from insurers, or they could drive new technologies and new forms of risk pooling through which health care services are provided and financed. DC health

  17. On Defining Mass

    Science.gov (United States)

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement surrounding the Large Hadron Collider at CERN is associated with discovering the mechanism responsible for the masses of the elementary particles. This paper will first briefly examine the leading definitions, pointing out their shortcomings. Then, utilizing relativity theory, it will propose—for consideration by the community of physicists—a conceptual definition of mass predicated on the more fundamental concept of energy, more fundamental in that everything that has mass has energy, yet not everything that has energy has mass.

  18. Implementing Software Defined Radio

    CERN Document Server

    Grayver, Eugene

    2013-01-01

    Software Defined Radio makes wireless communications easier, more efficient, and more reliable. This book bridges the gap between academic research and practical implementation. When beginning a project, practicing engineers, technical managers, and graduate students can save countless hours by considering the concepts presented in these pages. The author covers the myriad options and trade-offs available when selecting an appropriate hardware architecture. As demonstrated here, the choice between hardware- and software-centric architecture can mean the difference between meeting an aggressive schedule and bogging down in endless design iterations. Because of the author’s experience overseeing dozens of failed and successful developments, he is able to present many real-life examples. Some of the key concepts covered are: Choosing the right architecture for the market – laboratory, military, or commercial Hardware platforms – FPGAs, GPPs, specialized and hybrid devices Standardization efforts to ens...

  19. Defining cyber warfare

    Directory of Open Access Journals (Sweden)

    Dragan D. Mladenović

    2012-04-01

    Full Text Available Cyber conflicts represent a new kind of warfare that is technologically developing very rapidly. Such development results in more frequent and more intensive cyber attacks undertaken by states against adversary targets, with a wide range of diverse operations, from information operations to physical destruction of targets. Nevertheless, cyber warfare is waged through the application of the same means, techniques and methods as those used in cyber criminal, terrorism and intelligence activities. Moreover, it has a very specific nature that enables states to covertly initiate attacks against their adversaries. The starting point in defining doctrines, procedures and standards in the area of cyber warfare is determining its true nature. In this paper, a contribution to this effort was made through the analysis of the existing state doctrines and international practice in the area of cyber warfare towards the determination of its nationally acceptable definition.

  20. Software Defined Networking

    DEFF Research Database (Denmark)

    Caba, Cosmin Marius

    Network Service Providers (NSP) often choose to overprovision their networks instead of deploying proper Quality of Services (QoS) mechanisms that allow for traffic differentiation and predictable quality. This tendency of overprovisioning is not sustainable for the simple reason that network...... resources are limited. Hence, to counteract this trend, current QoS mechanisms must become simpler to deploy and operate, in order to motivate NSPs to employ QoS techniques instead of overprovisioning. Software Defined Networking (SDN) represents a paradigm shift in the way telecommunication and data...... generic perspective (e.g. service provisioning speed, resources availability). As a result, new mechanisms for providing QoS are proposed, solutions for SDN-specific QoS challenges are designed and tested, and new network management concepts are prototyped, all aiming to improve QoS for network services...

  1. Defining the Anthropocene

    Science.gov (United States)

    Lewis, Simon; Maslin, Mark

    2016-04-01

    Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

  2. Defining Information Security.

    Science.gov (United States)

    Lundgren, Björn; Möller, Niklas

    2017-11-15

    This article proposes a new definition of information security, the 'Appropriate Access' definition. Apart from providing the basic criteria for a definition-correct demarcation and meaning concerning the state of security-it also aims at being a definition suitable for any information security perspective. As such, it bridges the conceptual divide between so-called 'soft issues' of information security (those including, e.g., humans, organizations, culture, ethics, policies, and law) and more technical issues. Because of this it is also suitable for various analytical purposes, such as analysing possible security breaches, or for studying conflicting attitudes on security in an organization. The need for a new definition is demonstrated by pointing to a number of problems for the standard definition type of information security-the so-called CIA definition. Besides being too broad as well as too narrow, it cannot properly handle the soft issues of information security, nor recognize the contextual and normative nature of security.

  3. Teleology and Defining Sex.

    Science.gov (United States)

    Gamble, Nathan K; Pruski, Michal

    2018-07-01

    Disorders of sexual differentiation lead to what is often referred to as an intersex state. This state has medical, as well as some legal, recognition. Nevertheless, the question remains whether intersex persons occupy a state in between maleness and femaleness or whether they are truly men or women. To answer this question, another important conundrum needs to be first solved: what defines sex? The answer seems rather simple to most people, yet when morphology does not coincide with haplotypes, and genetics might not correlate with physiology the issue becomes more complex. This paper tackles both issues by establishing where the essence of sex is located and by superimposing that framework onto the issue of the intersex. This is achieved through giving due consideration to the biology of sexual development, as well as through the use of a teleological framework of the meaning of sex. Using a range of examples, the paper establishes that sex cannot be pinpointed to one biological variable but is rather determined by how the totality of one's biology is oriented towards biological reproduction. A brief consideration is also given to the way this situation could be comprehended from a Christian understanding of sex and suffering.

  4. A vector matching method for analysing logic Petri nets

    Science.gov (United States)

    Du, YuYue; Qi, Liang; Zhou, MengChu

    2011-11-01

    Batch processing function and passing value indeterminacy in cooperative systems can be described and analysed by logic Petri nets (LPNs). To directly analyse the properties of LPNs, the concept of transition enabling vector sets is presented and a vector matching method used to judge the enabling transitions is proposed in this article. The incidence matrix of LPNs is defined; an equation about marking change due to a transition's firing is given; and a reachable tree is constructed. The state space explosion is mitigated to a certain extent from directly analysing LPNs. Finally, the validity and reliability of the proposed method are illustrated by an example in electronic commerce.

  5. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    International Nuclear Information System (INIS)

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-01-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term

  6. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    Energy Technology Data Exchange (ETDEWEB)

    Sclafani, Francesco; Peckitt, Clare [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Cunningham, David, E-mail: david.cunningham@rmh.nhs.uk [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tait, Diana [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Giralt, Jordi [Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona (Spain); Glimelius, Bengt [University of Uppsala, Uppsala (Sweden); Keränen, Susana Roselló [Biomedical Research Institute INCLIVA, Department of Hematology and Medical Oncology, University of Valencia (Spain); Bateman, Andrew [Southampton General Hospital, Cancer Sciences Unit, University of Southampton (United Kingdom); Hickish, Tamas [Poole Hospital NHS Foundation Trust, Department of Medical Oncology, Bournemouth University (United Kingdom); Tabernero, Josep [Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona (Spain); Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian [The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  7. Defining an emerging disease.

    Science.gov (United States)

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future.

  8. Foxtail millet NF-Y families: genome-wide survey and evolution analyses identified two functional genes important in abiotic stresses

    Directory of Open Access Journals (Sweden)

    Zhi-Juan eFeng

    2015-12-01

    Full Text Available It was reported that Nuclear Factor Y (NF-Y genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica, an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam NtERD10, NtLEA5, NtCAT, NtSOD or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC and contents of chlorophyll, superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and malondialdehyde (MDA in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5 and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

  9. Molecular and functional analyses of novel anti-lipopolysaccharide factors in giant river prawn (Macrobrachium rosenbergii, De Man) and their expression responses under pathogen and temperature exposure.

    Science.gov (United States)

    Srisapoome, Prapansak; Klongklaew, Nawanith; Areechon, Nontawith; Wongpanya, Ratree

    2018-06-15

    obtained in this study, novel ALF genes were clearly identified. Analyses of their responses under pathogenic and temperature stresses demonstrated the binding and antimicrobial activities of these ALFs and the consequent physiological effects, indicating their crucial functional roles in the prawn immune system. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

  11. Definably compact groups definable in real closed fields.II

    OpenAIRE

    Barriga, Eliana

    2017-01-01

    We continue the analysis of definably compact groups definable in a real closed field $\\mathcal{R}$. In [3], we proved that for every definably compact definably connected semialgebraic group $G$ over $\\mathcal{R}$ there are a connected $R$-algebraic group $H$, a definable injective map $\\phi$ from a generic definable neighborhood of the identity of $G$ into the group $H\\left(R\\right)$ of $R$-points of $H$ such that $\\phi$ acts as a group homomorphism inside its domain. The above result and o...

  12. Statistical properties of coastal long waves analysed through sea-level time-gradient functions: exemplary analysis of the Siracusa, Italy, tide-gauge data

    Directory of Open Access Journals (Sweden)

    L. Bressan

    2016-01-01

    reconstructed sea level (RSL, the background slope (BS and the control function (CF. These functions are examined through a traditional spectral fast Fourier transform (FFT analysis and also through a statistical analysis, showing that they can be characterised by probability distribution functions PDFs such as the Student's t distribution (IS and RSL and the beta distribution (CF. As an example, the method has been applied to data from the tide-gauge station of Siracusa, Italy.

  13. Defining food literacy: A scoping review.

    Science.gov (United States)

    Truman, Emily; Lane, Daniel; Elliott, Charlene

    2017-09-01

    The term "food literacy" describes the idea of proficiency in food related skills and knowledge. This prevalent term is broadly applied, although its core elements vary from initiative to initiative. In light of its ubiquitous use-but varying definitions-this article establishes the scope of food literacy research by identifying all articles that define 'food literacy', analysing its key conceptualizations, and reporting outcomes/measures of this concept. A scoping review was conducted to identify all articles (academic and grey literature) using the term "food literacy". Databases included Medline, Pubmed, Embase, CAB Abstracts, CINAHL, Scopus, JSTOR, and Web of Science, and Google Scholar. Of 1049 abstracts, 67 studies were included. From these, data was extracted on country of origin, study type (methodological approach), primary target population, and the primary outcomes relating to food literacy. The majority of definitions of food literacy emphasize the acquisition of critical knowledge (information and understanding) (55%) over functional knowledge (skills, abilities and choices) (8%), although some incorporate both (37%). Thematic analysis of 38 novel definitions of food literacy reveals the prevalence of six themes: skills and behaviours, food/health choices, culture, knowledge, emotions, and food systems. Study outcomes largely focus on knowledge generating measures, with very few focusing on health related outcome measures. Current definitions of food literacy incorporate components of six key themes or domains and attributes of both critical and functional knowledge. Despite this broad definition of the term, most studies aiming to improve food literacy focus on knowledge related outcomes. Few articles address health outcomes, leaving an important gap (and opportunity) for future research in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Marital and Family Satisfaction as a Function of Work-Family Demands and Community Resources: Individual- and Couple-Level Analyses

    Science.gov (United States)

    Hostetler, Andrew J.; Desrochers, Stephan; Kopko, Kimberly; Moen, Phyllis

    2012-01-01

    This study uses individual- and couple-level analyses to examine the influence of work-family demands and community resources on marital and family satisfaction within a sample of dual-earner parents with dependent children (N = 260 couples, 520 individuals). Total couple work hours were strongly negatively associated with marital satisfaction for…

  15. Applying meta-pathway analyses through metagenomics to identify the functional properties of the major bacterial communities of a single spontaneous cocoa bean fermentation process sample.

    Science.gov (United States)

    Illeghems, Koen; Weckx, Stefan; De Vuyst, Luc

    2015-09-01

    A high-resolution functional metagenomic analysis of a representative single sample of a Brazilian spontaneous cocoa bean fermentation process was carried out to gain insight into its bacterial community functioning. By reconstruction of microbial meta-pathways based on metagenomic data, the current knowledge about the metabolic capabilities of bacterial members involved in the cocoa bean fermentation ecosystem was extended. Functional meta-pathway analysis revealed the distribution of the metabolic pathways between the bacterial members involved. The metabolic capabilities of the lactic acid bacteria present were most associated with the heterolactic fermentation and citrate assimilation pathways. The role of Enterobacteriaceae in the conversion of substrates was shown through the use of the mixed-acid fermentation and methylglyoxal detoxification pathways. Furthermore, several other potential functional roles for Enterobacteriaceae were indicated, such as pectinolysis and citrate assimilation. Concerning acetic acid bacteria, metabolic pathways were partially reconstructed, in particular those related to responses toward stress, explaining their metabolic activities during cocoa bean fermentation processes. Further, the in-depth metagenomic analysis unveiled functionalities involved in bacterial competitiveness, such as the occurrence of CRISPRs and potential bacteriocin production. Finally, comparative analysis of the metagenomic data with bacterial genomes of cocoa bean fermentation isolates revealed the applicability of the selected strains as functional starter cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Plasma Cell Alloantigen 1 and IL-10 Secretion Define Two Distinct Peritoneal B1a B Cell Subsets With Opposite Functions, PC1high Cells Being Protective and PC1low Cells Harmful for the Growing Fetus

    Directory of Open Access Journals (Sweden)

    Anne Schumacher

    2018-05-01

    Full Text Available B cells possess various immuno regulatory functions. However, research about their participation in tolerance induction toward the fetus is just emerging. Accumulating evidence supports the idea that B cells can play seemingly conflicting roles during pregnancy, either protecting or harming the fetus. Previous findings indicated the presence of two different peritoneal B cell subsets, defined by the expression of the plasma cell alloantigen 1 (PC1 and with distinct immune modulatory functions. Here, we aimed to study the participation of these two B cell subsets, on pregnancy outcome in a murine model of disturbed fetal tolerance. The frequencies and cell numbers of peritoneal and splenic CD19+IL-10+ and CD19+CD5+IL-10+PC1+ cells were assessed in virgin as well as normal pregnant (NP and abortion-prone (AP females during the course of gestation. Peritoneal PC1low or PC1high B1a B cells were sorted, analyzed for their ability to secrete IL-10 and adoptively transferred into NP or AP females. On gestation day (gd 12, the abortion rate as well as the frequencies and cell numbers of regulatory T cells, TH1 and TH17 cells were determined in spleens and decidua. In addition, mRNA expression of IL-10, TGF-β, IFN-γ, and TNF-α was analyzed in decidual tissue. Peritoneal CD19+IL-10+ and CD19+CD5+IL-10+PC1+ frequencies fluctuated during the progression of normal pregnancies while no significant changes were observed in spleen. AP females showed significantly reduced frequencies of both B cell populations and exhibited an altered peritoneal PC1high/PC1low ratio at gd10. Adoptive transfers of PC1low B1a B cells into NP females increased the abortion rate in association with a reduced splenic regulatory T/TH17 ratio. By contrast, the transfer of PC1high B1a B cells into AP females significantly diminished the fetal rejection rate and significantly reduced the numbers of splenic TH17 cells. Our results suggest that the peritoneum harbors two distinct B1a B

  17. Comparative functional analyses of ultrabithorax reveal multiple steps and paths to diversification of legs in the adaptive radiation of semi-aquatic insects.

    Science.gov (United States)

    Khila, Abderrahman; Abouheif, Ehab; Rowe, Locke

    2014-08-01

    Invasion of new ecological habitats is often associated with lineage diversification, yet the genetic changes underlying invasions and radiations are poorly understood. Over 200 million years ago, the semi-aquatic insects invaded water surface from a common terrestrial ancestor and diversified to exploit a wide array of niches. Here, we uncover the changes in regulation and function of the gene Ultrabithorax associated with both the invasion of water surface and the subsequent diversification of the group. In the common ancestor of the semi-aquatic insects, a novel deployment of Ubx protein in the mid-legs increased their length, thereby enhancing their role in water surface walking. In derived lineages that specialize in rowing on the open water, additional changes in the timing of Ubx expression further elongated the mid-legs thereby facilitating their function as oars. In addition, Ubx protein function was selectively reversed to shorten specific rear-leg segments, thereby enabling their function as rudders. These changes in Ubx have generated distinct niche-specialized morphologies that account for the remarkable diversification of the semi-aquatic insects. Therefore, changes in the regulation and function of a key developmental gene may facilitate both the morphological change necessary to transition to novel habitats and fuel subsequent morphological diversification. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  18. Exploration for novel genes and pathways involved in repair of x-ray damage by functional analyses of C. elegans genome

    International Nuclear Information System (INIS)

    Eki, T.

    2004-01-01

    Gene function suppression nematodes were produced by systematic RNA interference process (RNAi) of genes which included helicase gene group. Some of high sensitivity genes were identified by the result of function screening for X-ray sensitivity of the function suppression nematode. A complete length of cDNA was separated from the two novel genes, and all the base sequences were determined. It was cleared that one of the novel genes encodes RNA helicases protein which consists of 1,119 amino acids, and the other one encodes chromatin modeling ATPase protein which consists of 3,035 and 3,201 amino acids. Candidacy genes of about 14 pieces for the RNA helicase protein were identified by yeast two-hybrid process as the results of research for nematode protein which showed protein interaction. (M. Suetake)

  19. Proteins analysed as virtual knots

    Science.gov (United States)

    Alexander, Keith; Taylor, Alexander J.; Dennis, Mark R.

    2017-02-01

    Long, flexible physical filaments are naturally tangled and knotted, from macroscopic string down to long-chain molecules. The existence of knotting in a filament naturally affects its configuration and properties, and may be very stable or disappear rapidly under manipulation and interaction. Knotting has been previously identified in protein backbone chains, for which these mechanical constraints are of fundamental importance to their molecular functionality, despite their being open curves in which the knots are not mathematically well defined; knotting can only be identified by closing the termini of the chain somehow. We introduce a new method for resolving knotting in open curves using virtual knots, which are a wider class of topological objects that do not require a classical closure and so naturally capture the topological ambiguity inherent in open curves. We describe the results of analysing proteins in the Protein Data Bank by this new scheme, recovering and extending previous knotting results, and identifying topological interest in some new cases. The statistics of virtual knots in protein chains are compared with those of open random walks and Hamiltonian subchains on cubic lattices, identifying a regime of open curves in which the virtual knotting description is likely to be important.

  20. MPID-T2: a database for sequence-structure-function analyses of pMHC and TR/pMHC structures.

    Science.gov (United States)

    Khan, Javed Mohammed; Cheruku, Harish Reddy; Tong, Joo Chuan; Ranganathan, Shoba

    2011-04-15

    Sequence-structure-function information is critical in understanding the mechanism of pMHC and TR/pMHC binding and recognition. A database for sequence-structure-function information on pMHC and TR/pMHC interactions, MHC-Peptide Interaction Database-TR version 2 (MPID-T2), is now available augmented with the latest PDB and IMGT/3Dstructure-DB data, advanced features and new parameters for the analysis of pMHC and TR/pMHC structures. http://biolinfo.org/mpid-t2. shoba.ranganathan@mq.edu.au Supplementary data are available at Bioinformatics online.

  1. Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy. Cross-sectional Analyses of Baseline Data of the EUROCONDOR project

    DEFF Research Database (Denmark)

    Santos, Ana Rita; Ribeiro, Luisa; Bandello, Francesco

    2017-01-01

    Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2...... diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1...

  2. Detection of Differential Item Functioning on the Kirton Adaption-Innovation Inventory Using Multiple-Group Mean and Covariance Structure Analyses.

    Science.gov (United States)

    Chan, David

    2000-01-01

    Demonstrates how the mean and covariance structure analysis model of D. Sorbom (1974) can be used to detect uniform and nonuniform differential item functioning (DIF) on polytomous ordered response items assumed to approximate a continuous scale. Uses results from 773 civil service employees administered the Kirton Adaption-Innovation Inventory…

  3. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max.

    Directory of Open Access Journals (Sweden)

    Yungang Xu

    Full Text Available Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN, a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max, due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs, in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional

  4. SCALE: A modular code system for performing Standardized Computer Analyses for Licensing Evaluation. Volume 2, Part 3: Functional modules F16--F17; Revision 5

    International Nuclear Information System (INIS)

    1997-03-01

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automated the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system has been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.3 of the system

  5. SCALE: A modular code system for performing Standardized Computer Analyses for Licensing Evaluation. Volume 2, Part 3: Functional modules F16--F17; Revision 5

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automated the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system has been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.3 of the system.

  6. Functional Characterization of the Protein Product of the Prostate Carcinoma Gene Fusion TMPRSS2:ERG Using the Proteomic and Microarray Analyses

    Science.gov (United States)

    2009-07-01

    AD_________________ ( Leave blank) Award Number: W81XWH-08-1-0048 TITLE: Functional... Guava ™ FACS analyzer with the ViaCount™ kit (Millipore). As shown in Fig. 7, VCaP cells infected with ERG or ERGa once again failed to proliferate...and the cell numbers in each series were determined using the Guava ViaCount™ kit. Average values of the triplicate samples are shown. Milestone

  7. Cross-species functional analyses reveal shared and separate roles for Sox11 in frog primary neurogenesis and mouse cortical neuronal differentiation

    Directory of Open Access Journals (Sweden)

    Chao Chen

    2016-04-01

    Full Text Available A well-functioning brain requires production of the correct number and types of cells during development; cascades of transcription factors are essential for cellular coordination. Sox proteins are transcription factors that affect various processes in the development of the nervous system. Sox11, a member of the SoxC family, is expressed in differentiated neurons and supports neuronal differentiation in several systems. To understand how generalizable the actions of Sox11 are across phylogeny, its function in the development of the frog nervous system and the mouse cerebral cortex were compared. Expression of Sox11 is largely conserved between these species; in the developing frog, Sox11 is expressed in the neural plate, neural tube and throughout the segmented brain, while in the mouse cerebral cortex, Sox11 is expressed in differentiated zones, including the preplate, subplate, marginal zone and cortical plate. In both frog and mouse, data demonstrate that Sox11 supports a role in promoting neuronal differentiation, with Sox11-positive cells expressing pan-neural markers and becoming morphologically complex. However, frog and mouse Sox11 cannot substitute for one another; a functional difference likely reflected in sequence divergence. Thus, Sox11 appears to act similarly in subserving neuronal differentiation but is species-specific in frog neural development and mouse corticogenesis.

  8. INSULIN-SECRETION BY RAT ISLET ISOGRAFTS OF A DEFINED ENDOCRINE VOLUME AFTER TRANSPLANTATION TO 3 DIFFERENT SITES

    NARCIS (Netherlands)

    VANSUYLICHEM, PTR; STRUBBE, JH; HOUWING, H; WOLTERS, GHJ; VANSCHILFGAARDE, R

    1992-01-01

    We have analysed the graft function of rat islet isografts of identical and well-defined endocrine volumes after transplantation to three different sites (kidney, liver and spleen). Graft endocrine mass was determined by measuring the total islet volume prior to transplantation and was chosen to be

  9. Insulin secretion by rat islet isografts of a defined endocrine volume after transplantation to three different sites

    NARCIS (Netherlands)

    Suylichem, P.T.R. van; Strubbe, J.H.; Houwing, H.; Wolters, G.H.J.; Schilfgaarde, R. van

    1992-01-01

    We have analysed the graft function of rat islet isografts of identical and well-defined endocrine volumes after transplantation to three different sites (kidney, liver and spleen). Graft endocrine mass was determined by measuring the total islet volume prior to transplantation and was chosen to be

  10. Structure-Function Analyses of a Caffeic Acid O-Methyltransferase from Perennial Ryegrass Reveal the Molecular Basis for Substrate Preference[W][OA

    Science.gov (United States)

    Louie, Gordon V.; Bowman, Marianne E.; Tu, Yi; Mouradov, Aidyn; Spangenberg, German; Noel, Joseph P.

    2010-01-01

    Lignin forms from the polymerization of phenylpropanoid-derived building blocks (the monolignols), whose modification through hydroxylation and O-methylation modulates the chemical and physical properties of the lignin polymer. The enzyme caffeic acid O-methyltransferase (COMT) is central to lignin biosynthesis. It is often targeted in attempts to engineer the lignin composition of transgenic plants for improved forage digestibility, pulping efficiency, or utility in biofuel production. Despite intensive investigation, the structural determinants of the regiospecificity and substrate selectivity of COMT remain poorly defined. Reported here are x-ray crystallographic structures of perennial ryegrass (Lolium perenne) COMT (Lp OMT1) in open conformational state, apo- and holoenzyme forms and, most significantly, in a closed conformational state complexed with the products S-adenosyl-l-homocysteine and sinapaldehyde. The product-bound complex reveals the post-methyl-transfer organization of COMT’s catalytic groups with reactant molecules and the fully formed phenolic-ligand binding site. The core scaffold of the phenolic ligand forges a hydrogen-bonding network involving the 4-hydroxy group that anchors the aromatic ring and thereby permits only metahydroxyl groups to be positioned for transmethylation. While distal from the site of transmethylation, the propanoid tail substituent governs the kinetic preference of ryegrass COMT for aldehydes over alcohols and acids due to a single hydrogen bond donor for the C9 oxygenated moiety dictating the preference for an aldehyde. PMID:21177481

  11. Structure-function analyses of a caffeic acid O-methyltransferase from perennial ryegrass reveal the molecular basis for substrate preference.

    Science.gov (United States)

    Louie, Gordon V; Bowman, Marianne E; Tu, Yi; Mouradov, Aidyn; Spangenberg, German; Noel, Joseph P

    2010-12-01

    Lignin forms from the polymerization of phenylpropanoid-derived building blocks (the monolignols), whose modification through hydroxylation and O-methylation modulates the chemical and physical properties of the lignin polymer. The enzyme caffeic acid O-methyltransferase (COMT) is central to lignin biosynthesis. It is often targeted in attempts to engineer the lignin composition of transgenic plants for improved forage digestibility, pulping efficiency, or utility in biofuel production. Despite intensive investigation, the structural determinants of the regiospecificity and substrate selectivity of COMT remain poorly defined. Reported here are x-ray crystallographic structures of perennial ryegrass (Lolium perenne) COMT (Lp OMT1) in open conformational state, apo- and holoenzyme forms and, most significantly, in a closed conformational state complexed with the products S-adenosyl-L-homocysteine and sinapaldehyde. The product-bound complex reveals the post-methyl-transfer organization of COMT's catalytic groups with reactant molecules and the fully formed phenolic-ligand binding site. The core scaffold of the phenolic ligand forges a hydrogen-bonding network involving the 4-hydroxy group that anchors the aromatic ring and thereby permits only metahydroxyl groups to be positioned for transmethylation. While distal from the site of transmethylation, the propanoid tail substituent governs the kinetic preference of ryegrass COMT for aldehydes over alcohols and acids due to a single hydrogen bond donor for the C9 oxygenated moiety dictating the preference for an aldehyde.

  12. Mexsyco project: representation of power plan control-instrumentation functions. Bibliographical analysis and conclusions; Projet Mexsyco: representation des fonctions de controle-commande des centrales. Analyse bibliographique et conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Brunet, M

    1994-03-01

    The study covered in this paper is designed to review the current situation in terms of functional analysis, in order to find a functional analysis method for mechanical parts able to serve as a substrate for expressing operating safety constraints, time-related performance or any other tag of function description. This paper comprises three parts: The first is devoted to general notions of the formats used by the various functional analyses. It attempts to explain the three types of format: behavioural, structural and functional. It tackles the notions of trees and bottom-up and top-down approaches. It proposes examining the link between the expected functions of the systems and the hardware supporting these functions. It attempts to make a distinction between ``operators`` and ``operands`` enabling the notion of object to be linked to that of the three types of format seen above. It ends with a reminder of the distinction between semi-formal and formal. The second part analyses the current situation of functional analysis of the mechanical and control-instrumentation parts of power production plants, through a bibliographical search. The results of this second part are however disappointing. The purpose of the third part of the study is a prototype format built up from the considerations of the first two parts. This format meets our requirements better than those of the bibliographical analysis, but it could doubtless be improved: application of this format to RCV highlights its advantages, but also underlines the improvements needed. Given the deadlines of the Mexsyco project, the decision was taken to suspend development of this format for the time being and use a method currently being produced and based on use of the current functional breakdown (basic plant systems) and of a modular tree-structure representation of the control-instrumentation of a basic plant system. (author). 12 refs., 4 annexes.

  13. Functional analyses of the skin surface of the areola mammae: comparison between healthy adult male and female subjects and between healthy individuals and patients with atopic dermatitis.

    Science.gov (United States)

    Kikuchi, K; Tagami, H; Akaraphanth, R; Aiba, S

    2011-01-01

    Although the nipple and areola of the breast constitute a unique and prominent area on the chest, so far no study has been done on the functional properties of their skin surfaces. To study the stratum corneum (SC) covering the areola using noninvasive methods. Eighteen adult healthy subjects comprising nine men and nine women and 18 age- and sex-matched patients with atopic dermatitis (AD), none of whom had visible skin lesions, participated in the study. Transepidermal water loss (TEWL), skin surface hydration and skin surface lipid levels were measured on the areola and adjacent breast skin. The size of the skin surface corneocytes of these skin regions was assessed. All the healthy subjects showed significantly higher TEWL accompanied by smaller sized corneocytes on the areola than on the adjacent breast skin. Only female subjects revealed a significantly higher skin surface hydration state together with significantly increased skin surface lipid levels on the areola than on the adjacent breast skin. These sex differences were observed even in patients with AD. Comparison between healthy individuals and the patients with AD demonstrated higher TEWL, decreased skin surface hydration state and lower skin surface lipid levels associated with smaller sized corneocytes in the areola in the patients with AD, especially in male patients. In adults, the SC barrier function and SC water-binding capacity of the areola were functionally poorer than in the adjacent skin, being covered by smaller sized corneocytes and lower amounts of skin surface lipids, especially in men and in patients with AD. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  14. Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.

    Science.gov (United States)

    Jia, Xuanyan; Yao, Jianyun; Gao, Zengqiang; Liu, Guangfeng; Dong, Yu-Hui; Wang, Xiaoxue; Zhang, Heng

    2018-05-04

    Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite R X 4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two α-helices (α2 and α4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the R X 4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these α-helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family. © 2018 Jia et al.

  15. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  16. Mechanical analyses of pipeline repair and reinforcement with use of composite functionally graded materials; Analise mecanica de reforco de dutos submarinos com materiais compositos com gradacao funcional

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcos S.M. [Sondotecnica Engenharia de Solos S.A., Rio de Janeiro, RJ (Brazil); Roehl, Deane de Mesquita [Pontificia Universidade Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil)

    2008-07-01

    This work presents a methodology for design of stiffener sleeve constituted by functionally graded composite materials in offshore pipelines located in extreme-deep waters, where high mechanical resistance allied to an efficient system of thermal isolation is necessary, in view of the excellent thermomechanical behavior of composites. For the case of FGMs, due to continuous variation in its featuring, is necessary to employ an adapted model, based on a model typically adopted for conventional composites (Rule of Mixture), as the model idealized by Tamura, Tomato e Ozawa, the TTO model. In this report, the influence of geometric and materials parameters in mechanical behavior of pipelines under propagating collapse is analyzed. (author)

  17. Network class superposition analyses.

    Directory of Open Access Journals (Sweden)

    Carl A B Pearson

    Full Text Available Networks are often used to understand a whole system by modeling the interactions among its pieces. Examples include biomolecules in a cell interacting to provide some primary function, or species in an environment forming a stable community. However, these interactions are often unknown; instead, the pieces' dynamic states are known, and network structure must be inferred. Because observed function may be explained by many different networks (e.g., ≈ 10(30 for the yeast cell cycle process, considering dynamics beyond this primary function means picking a single network or suitable sample: measuring over all networks exhibiting the primary function is computationally infeasible. We circumvent that obstacle by calculating the network class ensemble. We represent the ensemble by a stochastic matrix T, which is a transition-by-transition superposition of the system dynamics for each member of the class. We present concrete results for T derived from boolean time series dynamics on networks obeying the Strong Inhibition rule, by applying T to several traditional questions about network dynamics. We show that the distribution of the number of point attractors can be accurately estimated with T. We show how to generate Derrida plots based on T. We show that T-based Shannon entropy outperforms other methods at selecting experiments to further narrow the network structure. We also outline an experimental test of predictions based on T. We motivate all of these results in terms of a popular molecular biology boolean network model for the yeast cell cycle, but the methods and analyses we introduce are general. We conclude with open questions for T, for example, application to other models, computational considerations when scaling up to larger systems, and other potential analyses.

  18. The optokinetic reflex as a tool for quantitative analyses of nervous system function in mice: application to genetic and drug-induced variation.

    Directory of Open Access Journals (Sweden)

    Hugh Cahill

    2008-04-01

    Full Text Available The optokinetic reflex (OKR, which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable. We describe a new type of OKR test apparatus in which computer-controlled visual stimuli and streamlined data analysis facilitate a relatively high throughput behavioral assay. We used this apparatus, in conjunction with infrared imaging, to quantify basic OKR stimulus-response characteristics for C57BL/6J and 129/SvEv mouse strains and for genetically engineered lines lacking one or more photoreceptor systems or with an alteration in cone spectral sensitivity. A second generation (F2 cross shows that the characteristic difference in OKR frequency between C57BL/6J and 129/SvEv is inherited as a polygenic trait. Finally, we demonstrate the sensitivity and high temporal resolution of the OKR for quantitative analysis of CNS drug action. These experiments show that the mouse OKR is well suited for neurologic testing in the context of drug discovery and large-scale phenotyping programs.

  19. Functional analyses in the milkweed bug Oncopeltus fasciatus (Hemiptera) support a role for Wnt signaling in body segmentation but not appendage development.

    Science.gov (United States)

    Angelini, David R; Kaufman, Thomas C

    2005-07-15

    Specification of the proximal-distal (PD) axis of insect appendages is best understood in Drosophila melanogaster, where conserved signaling molecules encoded by the genes decapentaplegic (dpp) and wingless (wg) play key roles. However, the development of appendages from imaginal discs as in Drosophila is a derived state, while more basal insects produce appendages from embryonic limb buds. Therefore, the universality of the Drosophila limb PD axis specification mechanism has been debated since dpp expression in more basal insect species differs dramatically from Drosophila. Here, we test the function of Wnt signaling in the development of the milkweed bug Oncopeltus fasciatus, a species with the basal state of appendage development from limb buds. RNA interference of wg and pangolin (pan) produce defects in the germband and eyes, but not in the appendages. Distal-less and dachshund, two genes regulated by Wg signaling in Drosophila and expressed in specific PD domains along the limbs of both species, are expressed normally in the limbs of pan-depleted Oncopeltus embryos. Despite these apparently paradoxical results, Armadillo protein, the transducer of Wnt signaling, does not accumulate properly in the nuclei of cells in the legs of pan-depleted embryos. In contrast, engrailed RNAi in Oncopeltus produces cuticular and appendage defects similar to Drosophila. Therefore, our data suggest that Wg signaling is functionally conserved in the development of the germband, while it is not essential in the specification of the limb PD axis in Oncopeltus and perhaps basal insects.

  20. Long-term Impact of Weight Loss Intervention on Changes in Cognitive Function: Exploratory Analyses from the Action for Health in Diabetes Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Espeland, Mark A; Carmichael, Owen; Hayden, Kathleen; Neiberg, Rebecca H; Newman, Anne B; Keller, Jeffery N; Wadden, Thomas A; Rapp, Stephen R; Hill, James O; Horton, Edward S; Johnson, Karen C; Wagenknecht, Lynne; Wing, Rena R

    2018-03-14

    Diabetes adversely impacts cognition. Lifestyle change can improve diabetes control and potentially improve cognition. We examined whether weight loss through reduced caloric intake and increased physical activity was associated with slower cognitive aging in older adults with type 2 diabetes mellitus. The Look AHEAD randomized controlled clinical trial delivered 10 years of intensive lifestyle intervention (ILI) that yielded long-term weight losses. During 5 years spanning the end of intervention and postintervention follow-up, repeated cognitive assessments were obtained in 1,091 individuals who had been assigned to ILI or a control condition of diabetes support and education (DSE). We compared the means and slopes of scores on cognitive testing over these repeated assessments. Compared with DSE, assignment to ILI was associated with a -0.082 SD deficit in mean global cognitive function across repeated assessments (p = .010). However, overweight (body mass index [BMI] memory. The behavioral weight loss intervention was associated with small relative deficits in cognitive function among individuals who were obese and marginally greater cognitive decline overall compared to control. ClinicalTrials.gov Identifier: NCT00017953.

  1. Thermochemistry analyses for transformation of C6 glucose compound into C9, C12 and C15 alkanes using density functional theory

    Science.gov (United States)

    Verma, Anand Mohan; Kishore, Nanda

    2017-02-01

    The hydrolysis of cellulose fraction of biomass yields C6 glucose which further can be transformed into long-chain hydrocarbons by C-C coupling. In this study, C6 glucose is transformed into three chain alkanes, namely, C9, C12 and C15 using C-C coupling reactions under the gas and aqueous phase milieus. The geometry optimisation and vibrational frequency calculations are carried out at well-known hybrid-GGA functional, B3LYP with the basis set of 6-31+g(d,p) under the density functional theory framework. The single point energetics are calculated at M05-2X/6-311+g(3df,2p) level of theory. All thermochemical properties are calculated over a wide range of temperature between 300 and 900 K at an interval of 100 K. The thermochemistry suggested that the aqueous phase behaviour is suitable for the hydrolysis of sugar into long-chain alkanes compared to gas-phase environment. The hydrodeoxygenation reactions under each reaction pathway are found as most favourable reactions in both phases; however, aqueous phase dominates over gas phase in all discussed thermodynamic parameters.

  2. Unconditional and Conditional Standards Using Cognitive Function Curves for the Modified Mini-Mental State Exam: Cross-Sectional and Longitudinal Analyses in Older Chinese Adults in Singapore.

    Science.gov (United States)

    Cheung, Yin Bun; Xu, Ying; Feng, Lei; Feng, Liang; Nyunt, Ma Shwe Zin; Chong, Mei Sian; Lim, Wee Shiong; Lee, Tih Shih; Yap, Philip; Yap, Keng Bee; Ng, Tze Pin

    2015-09-01

    The conventional practice of assessing cognitive status and monitoring change over time in older adults using normative values of the Mini-Mental State Exam (MMSE) based on age bands is imprecise. Moreover, population-based normative data on changes in MMSE score over time are scarce and crude because they do not include age- and education-specific norms. This study aims to develop unconditional standards for assessing current cognitive status and conditional standards that take prior MMSE score into account for assessing longitudinal change, with percentile curves as smooth functions of age. Cross-sectional and longitudinal data of a modified version of the MMSE for 2,026 older Chinese adults from the Singapore Longitudinal Aging Study, aged 55-84, in Singapore were used to estimate quantile regression coefficients and create unconditional standards and conditional standards. We presented MMSE percentile curves as a smooth function of age in education strata, for unconditional and conditional standards, based on quantile regression coefficient estimates. We found the 5th and 10th percentiles were more strongly associated with age and education than were higher percentiles. Model diagnostics demonstrated the accuracy of the standards. The development and use of unconditional and conditional standards should facilitate cognitive assessment in clinical practice and deserve further studies. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Large-scale brain network associated with creative insight: combined voxel-based morphometry and resting-state functional connectivity analyses.

    Science.gov (United States)

    Ogawa, Takeshi; Aihara, Takatsugu; Shimokawa, Takeaki; Yamashita, Okito

    2018-04-24

    Creative insight occurs with an "Aha!" experience when solving a difficult problem. Here, we investigated large-scale networks associated with insight problem solving. We recruited 232 healthy participants aged 21-69 years old. Participants completed a magnetic resonance imaging study (MRI; structural imaging and a 10 min resting-state functional MRI) and an insight test battery (ITB) consisting of written questionnaires (matchstick arithmetic task, remote associates test, and insight problem solving task). To identify the resting-state functional connectivity (RSFC) associated with individual creative insight, we conducted an exploratory voxel-based morphometry (VBM)-constrained RSFC analysis. We identified positive correlations between ITB score and grey matter volume (GMV) in the right insula and middle cingulate cortex/precuneus, and a negative correlation between ITB score and GMV in the left cerebellum crus 1 and right supplementary motor area. We applied seed-based RSFC analysis to whole brain voxels using the seeds obtained from the VBM and identified insight-positive/negative connections, i.e. a positive/negative correlation between the ITB score and individual RSFCs between two brain regions. Insight-specific connections included motor-related regions whereas creative-common connections included a default mode network. Our results indicate that creative insight requires a coupling of multiple networks, such as the default mode, semantic and cerebral-cerebellum networks.

  4. Defining asthma in genetic studies

    NARCIS (Netherlands)

    Koppelman, GH; Postma, DS; Meijer, G.

    1999-01-01

    Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

  5. Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.

    Science.gov (United States)

    Cai, Qiuyin; Wen, Wanqing; Qu, Shimian; Li, Guoliang; Egan, Kathleen M; Chen, Kexin; Deming, Sandra L; Shen, Hongbing; Shen, Chen-Yang; Gammon, Marilie D; Blot, William J; Matsuo, Keitaro; Haiman, Christopher A; Khoo, Ui Soon; Iwasaki, Motoki; Santella, Regina M; Zhang, Lina; Fair, Alecia Malin; Hu, Zhibin; Wu, Pei-Ei; Signorello, Lisa B; Titus-Ernstoff, Linda; Tajima, Kazuo; Henderson, Brian E; Chan, Kelvin Y K; Kasuga, Yoshio; Newcomb, Polly A; Zheng, Hong; Cui, Yong; Wang, Furu; Shieh, Ya-Lan; Iwata, Hiroji; Le Marchand, Loic; Chan, Sum Yin; Shrubsole, Martha J; Trentham-Dietz, Amy; Tsugane, Shoichiro; Garcia-Closas, Montserrat; Long, Jirong; Li, Chun; Shi, Jiajun; Huang, Bo; Xiang, Yong-Bing; Gao, Yu-Tang; Lu, Wei; Shu, Xiao-Ou; Zheng, Wei

    2011-02-15

    We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10⁻³⁰], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10⁻⁴], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. ©2011 AACR.

  6. Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain

    Directory of Open Access Journals (Sweden)

    Katarzyna Marta Bocian-Ostrzycka

    2015-10-01

    Full Text Available Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation – periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595 with a -propeller structure. The aim of presented work was to assess relations between HP0231 structure and function.We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C, a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in E. coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (Escherichia coli DsbA protein were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity.

  7. Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project.

    Science.gov (United States)

    Santos, Ana Rita; Ribeiro, Luísa; Bandello, Francesco; Lattanzio, Rosangela; Egan, Catherine; Frydkjaer-Olsen, Ulrik; García-Arumí, José; Gibson, Jonathan; Grauslund, Jakob; Harding, Simon P; Lang, Gabriele E; Massin, Pascale; Midena, Edoardo; Scanlon, Peter; Aldington, Stephen J; Simão, Sílvia; Schwartz, Christian; Ponsati, Berta; Porta, Massimo; Costa, Miguel Ângelo; Hernández, Cristina; Cunha-Vaz, José; Simó, Rafael

    2017-09-01

    This cross-sectional study evaluated the relationship between 1 ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2 ) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes. © 2017 by the American Diabetes Association.

  8. The Dark Side of the Mushroom Spring Microbial Mat: Life in the Shadow of Chlorophototrophs. II. Metabolic Functions of Abundant Community Members Predicted from Metagenomic Analyses.

    Science.gov (United States)

    Thiel, Vera; Hügler, Michael; Ward, David M; Bryant, Donald A

    2017-01-01

    Microbial mat communities in the effluent channels of Octopus and Mushroom Springs within the Lower Geyser Basin of Yellowstone National Park have been extensively characterized. Previous studies have focused on the chlorophototrophic organisms of the phyla Cyanobacteria and Chloroflexi . However, the diversity and metabolic functions of the other portion of the community in the microoxic/anoxic region of the mat are poorly understood. We recently described the diverse but extremely uneven microbial assemblage in the undermat of Mushroom Spring based on 16S rRNA amplicon sequences, which was dominated by Roseiflexus members, filamentous anoxygenic chlorophototrophs. In this study, we analyzed the orange-colored undermat portion of the community of Mushroom Spring mats in a genome-centric approach and discuss the metabolic potentials of the major members. Metagenome binning recovered partial genomes of all abundant community members, ranging in completeness from ~28 to 96%, and allowed affiliation of function with taxonomic identity even for representatives of novel and Candidate phyla. Less complete metagenomic bins correlated with high microdiversity. The undermat portion of the community was found to be a mixture of phototrophic and chemotrophic organisms, which use bicarbonate as well as organic carbon sources derived from different cell components and fermentation products. The presence of rhodopsin genes in many taxa strengthens the hypothesis that light energy is of major importance. Evidence for the usage of all four bacterial carbon fixation pathways was found in the metagenome. Nitrogen fixation appears to be limited to Synechococcus spp. in the upper mat layer and Thermodesulfovibrio sp. in the undermat, and nitrate/nitrite metabolism was limited. A closed sulfur cycle is indicated by biological sulfate reduction combined with the presence of genes for sulfide oxidation mainly in phototrophs. Finally, a variety of undermat microorganisms have genes for

  9. The Dark Side of the Mushroom Spring Microbial Mat: Life in the Shadow of Chlorophototrophs. II. Metabolic Functions of Abundant Community Members Predicted from Metagenomic Analyses

    Directory of Open Access Journals (Sweden)

    Vera Thiel

    2017-06-01

    Full Text Available Microbial mat communities in the effluent channels of Octopus and Mushroom Springs within the Lower Geyser Basin of Yellowstone National Park have been extensively characterized. Previous studies have focused on the chlorophototrophic organisms of the phyla Cyanobacteria and Chloroflexi. However, the diversity and metabolic functions of the other portion of the community in the microoxic/anoxic region of the mat are poorly understood. We recently described the diverse but extremely uneven microbial assemblage in the undermat of Mushroom Spring based on 16S rRNA amplicon sequences, which was dominated by Roseiflexus members, filamentous anoxygenic chlorophototrophs. In this study, we analyzed the orange-colored undermat portion of the community of Mushroom Spring mats in a genome-centric approach and discuss the metabolic potentials of the major members. Metagenome binning recovered partial genomes of all abundant community members, ranging in completeness from ~28 to 96%, and allowed affiliation of function with taxonomic identity even for representatives of novel and Candidate phyla. Less complete metagenomic bins correlated with high microdiversity. The undermat portion of the community was found to be a mixture of phototrophic and chemotrophic organisms, which use bicarbonate as well as organic carbon sources derived from different cell components and fermentation products. The presence of rhodopsin genes in many taxa strengthens the hypothesis that light energy is of major importance. Evidence for the usage of all four bacterial carbon fixation pathways was found in the metagenome. Nitrogen fixation appears to be limited to Synechococcus spp. in the upper mat layer and Thermodesulfovibrio sp. in the undermat, and nitrate/nitrite metabolism was limited. A closed sulfur cycle is indicated by biological sulfate reduction combined with the presence of genes for sulfide oxidation mainly in phototrophs. Finally, a variety of undermat

  10. Functional Analyses of Resurrected and Contemporary Enzymes Illuminate an Evolutionary Path for the Emergence of Exolysis in Polysaccharide Lyase Family 2.

    Science.gov (United States)

    McLean, Richard; Hobbs, Joanne K; Suits, Michael D; Tuomivaara, Sami T; Jones, Darryl R; Boraston, Alisdair B; Abbott, D Wade

    2015-08-28

    Family 2 polysaccharide lyases (PL2s) preferentially catalyze the β-elimination of homogalacturonan using transition metals as catalytic cofactors. PL2 is divided into two subfamilies that have been generally associated with secretion, Mg(2+) dependence, and endolysis (subfamily 1) and with intracellular localization, Mn(2+) dependence, and exolysis (subfamily 2). When present within a genome, PL2 genes are typically found as tandem copies, which suggests that they provide complementary activities at different stages along a catabolic cascade. This relationship most likely evolved by gene duplication and functional divergence (i.e. neofunctionalization). Although the molecular basis of subfamily 1 endolytic activity is understood, the adaptations within the active site of subfamily 2 enzymes that contribute to exolysis have not been determined. In order to investigate this relationship, we have conducted a comparative enzymatic analysis of enzymes dispersed within the PL2 phylogenetic tree and elucidated the structure of VvPL2 from Vibrio vulnificus YJ016, which represents a transitional member between subfamiles 1 and 2. In addition, we have used ancestral sequence reconstruction to functionally investigate the segregated evolutionary history of PL2 progenitor enzymes and illuminate the molecular evolution of exolysis. This study highlights that ancestral sequence reconstruction in combination with the comparative analysis of contemporary and resurrected enzymes holds promise for elucidating the origins and activities of other carbohydrate active enzyme families and the biological significance of cryptic metabolic pathways, such as pectinolysis within the zoonotic marine pathogen V. vulnificus. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. 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.

  12. Genome-Wide Identification of Cyclic Nucleotide-Gated Ion Channel Gene Family in Wheat and Functional Analyses of TaCNGC14 and TaCNGC16

    Directory of Open Access Journals (Sweden)

    Jia Guo

    2018-01-01

    Full Text Available Cyclic nucleotide gated channels (CNGCs play multifaceted roles in plants, particularly with respect to signaling processes associated with abiotic stress signaling and during host-pathogen interactions. Despite key roles during plant survival and response to environment, little is known about the activity and function of CNGC family in common wheat (Triticum aestivum L., a key stable food around the globe. In this study, we performed a genome-wide identification of CNGC family in wheat and identified a total 47 TaCNGCs in wheat, classifying these genes into four major groups (I–IV with two sub-groups (IVa and IVb. Sequence analysis revealed the presence of several conserved motifs, including a phosphate binding cassette (PBC and a “hinge” region, both of which have been hypothesized to be critical for the function of wheat CNGCs. During wheat infection with Pst, the transcript levels of TaCNGC14 and TaCNGC16, both members of group IVb, showed significant induction during a compatible interaction, while a reduction in gene expression was observed in incompatible interactions. In addition, TaCNGC14 and TaCNGC16 mRNA accumulation was significantly influenced by exogenously applied hormones, including abscisic acid (ABA, methyl jasmonate (MeJA, and salicylic acid (SA, suggesting a role in hormone signaling and/or perception. Silencing of TaCNGC14 and TaCNGC16 limited Pst growth and increased wheat resistance against Pst. The results presented herein contribute to our understanding of the wheat CNGC gene family and the mechanism of TaCNGCs signaling during wheat-Pst interaction.

  13. MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression.

    Directory of Open Access Journals (Sweden)

    Christopher R Shaler

    2017-06-01

    Full Text Available Superantigens (SAgs are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS. Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB; ii the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT or γδ T cells, and is characterized by production of interferon (IFN-γ, tumor necrosis factor (TNF-α and interleukin (IL-2, but not IL-17A; iii high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1 participation, is required for MAIT cell activation; iv MAIT cell responses to SEB can occur in a T cell receptor (TCR Vβ-specific manner but are largely contributed by IL-12 and IL-18; v as MAIT cells are primed by SAgs, they also begin to

  14. Novel nucleotide and amino acid covariation between the 5'UTR and the NS2/NS3 proteins of hepatitis C virus: bioinformatic and functional analyses.

    Directory of Open Access Journals (Sweden)

    Hung-Yu Sun

    Full Text Available Molecular covariation of highly polymorphic viruses is thought to have crucial effects on viral replication and fitness. This study employs association rule data mining of hepatitis C virus (HCV sequences to search for specific evolutionary covariation and then tests functional relevance on HCV replication. Data mining is performed between nucleotides in the untranslated regions 5' and 3'UTR, and the amino acid residues in the non-structural proteins NS2, NS3 and NS5B. Results indicate covariance of the 243(rd nucleotide of the 5'UTR with the 14(th, 41(st, 76(th, 110(th, 211(th and 212(th residues of NS2 and with the 71(st, 175(th and 621(st residues of NS3. Real-time experiments using an HCV subgenomic system to quantify viral replication confirm replication regulation for each covariant pair between 5'UTR₂₄₃ and NS2-41, -76, -110, -211, and NS3-71, -175. The HCV subgenomic system with/without the NS2 region shows that regulatory effects vanish without NS2, so replicative modulation mediated by HCV 5'UTR₂₄₃ depends on NS2. Strong binding of the NS2 variants to HCV RNA correlates with reduced HCV replication whereas weak binding correlates with restoration of HCV replication efficiency, as determined by RNA-protein immunoprecipitation assay band intensity. The dominant haplotype 5'UTR₂₄₃-NS2-41-76-110-211-NS3-71-175 differs according to the HCV genotype: G-Ile-Ile-Ile-Gly-Ile-Met for genotype 1b and A-Leu-Val-Leu-Ser-Val-Leu for genotypes 1a, 2a and 2b. In conclusion, 5'UTR₂₄₃ co-varies with specific NS2/3 protein amino acid residues, which may have significant structural and functional consequences for HCV replication. This unreported mechanism involving HCV replication possibly can be exploited in the development of advanced anti-HCV medication.

  15. Proteomic analyses for profiling regulated proteins/enzymes by Fucus vesiculosus fucoidan in B16 melanoma cells: A combination of enzyme kinetics functional study.

    Science.gov (United States)

    Wang, Zhi-Jiang; Zheng, Li; Yang, Jun-Mo; Kang, Yani; Park, Yong-Doo

    2018-06-01

    Fucoidans are complex sulfated polysaccharides that have a wide range of biological activities. Previously, we reported the various effects of Fucus vesiculosus fucoidan on tyrosinase and B16 melanoma cells. In this study, to identify fucoidan-targeted proteins in B16 melanoma cells, we performed a proteomics study and integrated enzyme kinetics. We detected 19 candidate proteins dysregulated by fucoidan treatment. Among the probed proteins, the enzyme kinetics of two candidate enzymes, namely lactate dehydrogenase (LDH) as an upregulated protein and superoxide dismutase (SOD) as a downregulated enzyme, were determined. The enzyme kinetics results showed that Fucus vesiculosus fucoidan significantly inhibited LDH catalytic function while it did not affect SOD activity even at a high dose, while only slightly decreased activity (up to 10%) at a low dose. Based on our previous and present observations, fucoidan could inhibit B16 melanoma cells growth via regulating proteins/enzymes expression levels such as LDH and SOD known as cell survival biomarkers. Interestingly, both expression level and enzyme catalytic activity of LDH were regulated by fucoidan, which could directly induce the apoptotic effect on B16 melanoma cells along with SOD downregulation. This study highlights how combining proteomics with enzyme kinetics can yield valuable insights into fucoidan targets. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Analysing the Conversion of a Cultural Heritage to a Multi-functional Complex in the Context of Sustainability: Example of Fiume Veneto

    Directory of Open Access Journals (Sweden)

    Yasemen SAY ÖZER

    2011-01-01

    Full Text Available Fiume Veneto, was established on the banks of the river Fiume near the city of Pordenone in northern Italy. What makes this settlement distinctive is the huge yarn factory which was founded sometime between 1880 and 1885. The textile factory has offices and a clean electrical power plant (hydroelectric, both located on an island of about 100,000 square metres. There is also a building located outside the factory, in which there had been a grain mill serving the locals since the XIIIth century up until its closure in 1999. Following its closure, Isola del Fiume Company purchased the former textile factory together with the island in order to construct a multi-functional complex. In 2003, The City Council Planning Committee and the Italian Chamber of Architects decided to organize an international ‘architectural design competition’ under the supervision and policy of the International Union of Architects. The aim was to decide the best strategy to reuse the property as a whole and in consideration with the economic viability, an important criterion for the company. After setting up a jury, a programme was announced which included housing, facilities, the renovation of the mill and hydroelectric plant, the establishment/protection of green spaces, sports facilities, a civic centre and town hall, a museum and an auditorium as well as the necessary infrastructure related to the new development. The main theme of this article is an architectural competition in the context of sustainability and the ways in which structural comfort is achieved in the architectural solutions provided.

  17. Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa.

    Science.gov (United States)

    Riveron, Jacob M; Ibrahim, Sulaiman S; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J; Ishak, Intan H; Wondji, Charles S

    2017-06-07

    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes ( CYP6P9a and CYP6P9b ) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. Copyright © 2017 Riveron et al.

  18. The dopaminergic system in patients with functional dyspepsia analysed by single photon emission computed tomography (SPECT) and an alpha-methyl-para-tyrosine (AMPT) challenge test

    International Nuclear Information System (INIS)

    Braak, Breg; Klooker, Tamira K.; Booij, Jan; Wijngaard, Rene M.J. van den; Boeckxstaens, Guy E.E.

    2012-01-01

    Functional dyspepsia (FD) is a chronic condition characterized by upper abdominal symptoms without an identifiable cause. While the serotonergic system is thought to play a key role in the regulation of gut physiology, the role of the dopaminergic system, which is important in the regulation of visceral pain and stress, is under-studied. Therefore, this study investigated the dopaminergic system and its relationship with drinking capacity and symptoms in FD patients. In FD patients and healthy volunteers (HV) the dopaminergic system was investigated by in-vivo assessment of central dopamine D2 receptors (D2Rs) with [ 123 I]IBZM SPECT and by an acute, but reversible, dopamine depletion alpha-methyl-para-tyrosine (AMPT) challenge test. A nutrient drink test was performed to investigate the association between maximal ingested volume, evoked symptoms, and D2Rs. The HV subjects comprised 12 women and 8 men (mean age 31 ± 3 years), and the FD patients comprised 5 women and 3 men (mean age 39 ± 5 years). The FD patients had a lower left plus right average striatal binding potential (BP NP ) for the caudate nucleus (p = 0.02), but not for putamen (p = 0.15), which in the FD patients was correlated with maximal ingested volume (r = 0.756, p = 0.03). The D2R BP NP in the putamen was correlated with nausea (r = 0.857, p = 0.01). The acute dopamine depletion test, however, failed to reveal differences in prolactin release between the FD patients and the HV subjects. These preliminary data suggest that chronic rather than acute alterations in the dopaminergic system may be involved in the pathogenesis of FD. Further studies are required to reproduce our novel findings and to evaluate to what extent the dopaminergic changes may be secondary to abnormalities in serotonergic pathways. (orig.)

  19. Re-evaluating a vision-related quality of life questionnaire with item response theory (IRT and differential item functioning (DIF analyses

    Directory of Open Access Journals (Sweden)

    Knol Dirk L

    2011-09-01

    Full Text Available Abstract Background For the Low Vision Quality Of Life questionnaire (LVQOL it is unknown whether the psychometric properties are satisfactory when an item response theory (IRT perspective is considered. This study evaluates some essential psychometric properties of the LVQOL questionnaire in an IRT model, and investigates differential item functioning (DIF. Methods Cross-sectional data were used from an observational study among visually-impaired patients (n = 296. Calibration was performed for every dimension of the LVQOL in the graded response model. Item goodness-of-fit was assessed with the S-X2-test. DIF was assessed on relevant background variables (i.e. age, gender, visual acuity, eye condition, rehabilitation type and administration type with likelihood-ratio tests for DIF. The magnitude of DIF was interpreted by assessing the largest difference in expected scores between subgroups. Measurement precision was assessed by presenting test information curves; reliability with the index of subject separation. Results All items of the LVQOL dimensions fitted the model. There was significant DIF on several items. For two items the maximum difference between expected scores exceeded one point, and DIF was found on multiple relevant background variables. Item 1 'Vision in general' from the "Adjustment" dimension and item 24 'Using tools' from the "Reading and fine work" dimension were removed. Test information was highest for the "Reading and fine work" dimension. Indices for subject separation ranged from 0.83 to 0.94. Conclusions The items of the LVQOL showed satisfactory item fit to the graded response model; however, two items were removed because of DIF. The adapted LVQOL with 21 items is DIF-free and therefore seems highly appropriate for use in heterogeneous populations of visually impaired patients.

  20. Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa

    Science.gov (United States)

    Riveron, Jacob M.; Ibrahim, Sulaiman S.; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J.; Ishak, Intan H.; Wondji, Charles S.

    2017-01-01

    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. PMID:28428243

  1. The dopaminergic system in patients with functional dyspepsia analysed by single photon emission computed tomography (SPECT) and an alpha-methyl-para-tyrosine (AMPT) challenge test

    Energy Technology Data Exchange (ETDEWEB)

    Braak, Breg; Klooker, Tamira K. [Academic Medical Center, Department of Gastroenterology and Hepatology, Amsterdam (Netherlands); Booij, Jan [Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands); Wijngaard, Rene M.J. van den [Academic Medical Center, Tytgat Institute of Liver and Intestinal Research, Amsterdam (Netherlands); Boeckxstaens, Guy E.E. [Academic Medical Center, Department of Gastroenterology and Hepatology, Amsterdam (Netherlands); University Hospital Leuven, Catholic University Leuven, Department of Gastroenterology, Leuven (Belgium)

    2012-04-15

    Functional dyspepsia (FD) is a chronic condition characterized by upper abdominal symptoms without an identifiable cause. While the serotonergic system is thought to play a key role in the regulation of gut physiology, the role of the dopaminergic system, which is important in the regulation of visceral pain and stress, is under-studied. Therefore, this study investigated the dopaminergic system and its relationship with drinking capacity and symptoms in FD patients. In FD patients and healthy volunteers (HV) the dopaminergic system was investigated by in-vivo assessment of central dopamine D2 receptors (D2Rs) with [{sup 123}I]IBZM SPECT and by an acute, but reversible, dopamine depletion alpha-methyl-para-tyrosine (AMPT) challenge test. A nutrient drink test was performed to investigate the association between maximal ingested volume, evoked symptoms, and D2Rs. The HV subjects comprised 12 women and 8 men (mean age 31 {+-} 3 years), and the FD patients comprised 5 women and 3 men (mean age 39 {+-} 5 years). The FD patients had a lower left plus right average striatal binding potential (BP{sub NP}) for the caudate nucleus (p = 0.02), but not for putamen (p = 0.15), which in the FD patients was correlated with maximal ingested volume (r = 0.756, p = 0.03). The D2R BP{sub NP} in the putamen was correlated with nausea (r = 0.857, p = 0.01). The acute dopamine depletion test, however, failed to reveal differences in prolactin release between the FD patients and the HV subjects. These preliminary data suggest that chronic rather than acute alterations in the dopaminergic system may be involved in the pathogenesis of FD. Further studies are required to reproduce our novel findings and to evaluate to what extent the dopaminergic changes may be secondary to abnormalities in serotonergic pathways. (orig.)

  2. Theoretical approaches to elections defining

    OpenAIRE

    Natalya V. Lebedeva

    2011-01-01

    Theoretical approaches to elections defining develop the nature, essence and content of elections, help to determine their place and a role as one of the major national law institutions in democratic system.

  3. Theoretical approaches to elections defining

    Directory of Open Access Journals (Sweden)

    Natalya V. Lebedeva

    2011-01-01

    Full Text Available Theoretical approaches to elections defining develop the nature, essence and content of elections, help to determine their place and a role as one of the major national law institutions in democratic system.

  4. Defining Modules, Modularity and Modularization

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth; Pedersen, Per Erik Elgård

    The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization.......The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization....

  5. 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.

  6. On Undefined and Meaningless in Lambda Definability

    OpenAIRE

    de Vries, Fer-Jan

    2016-01-01

    We distinguish between undefined terms as used in lambda definability of partial recursive functions and meaningless terms as used in infinite lambda calculus for the infinitary terms models that generalise the Bohm model. While there are uncountable many known sets of meaningless terms, there are four known sets of undefined terms. Two of these four are sets of meaningless terms. In this paper we first present set of sufficient conditions for a set of lambda terms to se...

  7. Defining safety goals. 2. Basic Consideration on Defining Safety Goals

    International Nuclear Information System (INIS)

    Hakata, T.

    2001-01-01

    cancer and severe hereditary effects are 10 x 10 -2 /Sv and 1.3 x10 -2 /Sv, respectively. The basic safety goals can be expressed by the complementary accumulative distribution function (CCDF) of dose versus frequencies of events: Pc(C > Cp) 5 (Cp/Co) -α . The aversion factor a is here expressed by the following arbitrary equation, which gives a polynomial curve of the order of m on a logarithmic plane: α = a+b(log(Cp/Co)) m , where: Pc = CCDF frequency for Cp (/yr), Cp = dose (mSv), Co = Cp for Pc =1, a, b, m = constants. Figure 1 shows a typical tolerable risk profile (risk limit curve), which is drawn so that all the points obtained in the previous discussions are above the curve (Co=1, a=1, b=0.0772, and m = 2). Safety criteria by ANS (Ref. 2) and SHE (Ref. 3) are shown in Fig. 1 for comparison. An aversion of a factor of 2 is resulted between 1 mSv and 1 Sv. No ALARA is included, which must be considered in defining specific safety goals. The frequency of a single class of events must be lower than the CCDF profile, and a curve lower by a factor of 10 is drawn in Fig. 1. The doses referenced in the current Japanese safety guidelines and site criteria are shown in Fig. 1. The referenced doses seem reasonable, considering the conservatism in the analysis of design-basis accidents. Specific safety goals for each sort of facility can be defined based on the basic safety goals, reflecting the characteristics of the facilities and considering ALARA. The indexes of engineering terms, such as CMF and LERF, are preferable for nuclear power plants, although interpretation from dose to the engineering terms is needed. Other indexes may be used (such as frequency of criticality accidents, etc.) for facilities except for power plants. The applicability of safety goals will thus be improved. Figure 2 shows the relative risk factors (1, 1%, and 0.1%) versus the severity of radiation effects. This might indicate the adequacy of the risk factors. The absolute risk limits, which

  8. Defining Plagiarism: A Literature Review

    Directory of Open Access Journals (Sweden)

    Akbar Akbar

    2018-02-01

    Full Text Available Plagiarism has repeatedly occurred in Indonesia, resulting in focusing on such academic misbehavior as a “central issue” in Indonesian higher education. One of the issues of addressing plagiarism in higher education is that there is a confusion of defining plagiarism. It seems that Indonesian academics had different perception when defining plagiarism. This article aims at exploring the issue of plagiarism by helping define plagiarism to address confusion among Indonesian academics. This article applies literature review by firs finding relevant articles after identifying databases for literature searching. After the collection of required articles for review, the articles were synthesized before presenting the findings. This study has explored the definition of plagiarism in the context of higher education. This research found that plagiarism is defined in the relation of criminal acts. The huge numbers of discursive features used position plagiaristic acts as an illegal deed. This study also found that cultural backgrounds and exposure to plagiarism were influential in defining plagiarism.

  9. Molecular ecological network analyses.

    Science.gov (United States)

    Deng, Ye; Jiang, Yi-Huei; Yang, Yunfeng; He, Zhili; Luo, Feng; Zhou, Jizhong

    2012-05-30

    Understanding the interaction among different species within a community and their responses to environmental changes is a central goal in ecology. However, defining the network structure in a microbial community is very challenging due to their extremely high diversity and as-yet uncultivated status. Although recent advance of metagenomic technologies, such as high throughout sequencing and functional gene arrays, provide revolutionary tools for analyzing microbial community structure, it is still difficult to examine network interactions in a microbial community based on high-throughput metagenomics data. Here, we describe a novel mathematical and bioinformatics framework to construct ecological association networks named molecular ecological networks (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other network construction methods, this approach is remarkable in that the network is automatically defined and robust to noise, thus providing excellent solutions to several common issues associated with high-throughput metagenomics data. We applied it to determine the network structure of microbial communities subjected to long-term experimental warming based on pyrosequencing data of 16 S rRNA genes. We showed that the constructed MENs under both warming and unwarming conditions exhibited topological features of scale free, small world and modularity, which were consistent with previously described molecular ecological networks. Eigengene analysis indicated that the eigengenes represented the module profiles relatively well. In consistency with many other studies, several major environmental traits including temperature and soil pH were found to be important in determining network interactions in the microbial communities examined. To facilitate its application by the scientific community, all these methods and statistical tools have been integrated into a comprehensive Molecular Ecological Network Analysis Pipeline (MENAP), which is open

  10. The Potential Use of Legitimate Force for the Preservation of Order: Defining the Inherent Role of Public Police Through Policing Functions that cannot be Carried out by Private Police

    Directory of Open Access Journals (Sweden)

    Jasmina Arnež

    2016-12-01

    Full Text Available In the UK, private policing institutions have been rapidly increasing since the 1980s, so the lines between public- and private police have been blurred. This paper explores whether there is a policing function that is inherent in public police and if so, why it occupies this position. It integrates Rousseau’s social contract theory, Bittner’s definition of police functions, Brodeur’s reasoning on force and Loader and Walker’s concept of ‘policing as public good’ to argue that the potential use of legitimate force for the preservation of order is the function intrinsic to public police. It shows why it cannot and should not be carried out by private police and outlines how it depends on police legitimacy. It concludes with an abstract rethinking of public-state-police relations to determine that this function remains in the realm of public policing.

  11. Modular Software-Defined Radio

    Directory of Open Access Journals (Sweden)

    Rhiemeier Arnd-Ragnar

    2005-01-01

    Full Text Available In view of the technical and commercial boundary conditions for software-defined radio (SDR, it is suggestive to reconsider the concept anew from an unconventional point of view. The organizational principles of signal processing (rather than the signal processing algorithms themselves are the main focus of this work on modular software-defined radio. Modularity and flexibility are just two key characteristics of the SDR environment which extend smoothly into the modeling of hardware and software. In particular, the proposed model of signal processing software includes irregular, connected, directed, acyclic graphs with random node weights and random edges. Several approaches for mapping such software to a given hardware are discussed. Taking into account previous findings as well as new results from system simulations presented here, the paper finally concludes with the utility of pipelining as a general design guideline for modular software-defined radio.

  12. Defining and Classifying Interest Groups

    DEFF Research Database (Denmark)

    Baroni, Laura; Carroll, Brendan; Chalmers, Adam

    2014-01-01

    The interest group concept is defined in many different ways in the existing literature and a range of different classification schemes are employed. This complicates comparisons between different studies and their findings. One of the important tasks faced by interest group scholars engaged...... in large-N studies is therefore to define the concept of an interest group and to determine which classification scheme to use for different group types. After reviewing the existing literature, this article sets out to compare different approaches to defining and classifying interest groups with a sample...... in the organizational attributes of specific interest group types. As expected, our comparison of coding schemes reveals a closer link between group attributes and group type in narrower classification schemes based on group organizational characteristics than those based on a behavioral definition of lobbying....

  13. ON DEFINING S-SPACES

    Directory of Open Access Journals (Sweden)

    Francesco Strati

    2013-05-01

    Full Text Available The present work is intended to be an introduction to the Superposition Theory of David Carfì. In particular I shall depict the meaning of his brand new theory, on the one hand in an informal fashion and on the other hand by giving a formal approach of the algebraic structure of the theory: the S-linear algebra. This kind of structure underpins the notion of S-spaces (or Carfì-spaces by defining both its properties and its nature. Thus I shall define the S-triple as the fundamental principle upon which the S-linear algebra is built up.

  14. Impact of a systolic parameter, defined as the ratio of right brachial pre-ejection period to ejection time, on the relationship between brachial-ankle pulse wave velocity and left ventricular diastolic function.

    Science.gov (United States)

    Hsu, Po-Chao; Lin, Tsung-Hsien; Lee, Chee-Siong; Chu, Chun-Yuan; Su, Ho-Ming; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

    2011-04-01

    Arterial stiffness is correlated with left ventricular (LV) diastolic function as well as susceptibility to LV systolic function. Therefore, if LV systolic function is not known, the relationship between arterial stiffness and LV diastolic function is difficult to determine. A total of 260 patients were included in the study. The brachial-ankle pulse wave velocity (baPWV) and the ratio of right brachial pre-ejection period to ejection time (rbPEP/rbET) were measured using an ABI-form device. Patients were classified into four groups. Groups 1, 2, 3 and 4 were patients with rbPEP/rbET and baPWV below the median, rbPEP/rbET above but baPWV below the median, rbPET/rbET below but baPWV above the median, and rbPET/rbET and baPWV above the median, respectively. The LV ejection fractions in groups 1 and 3 were higher than those in groups 2 and 4 (Pwave velocity to Ea that were comparable to those in groups 3 and 4. In conclusion, rbPEP/rbET had an impact on the relationship between baPWV and LV diastolic function. In patients with high rbPEP/rbET but low baPWV, low baPWV may not indicate good LV diastolic function but implies that cardiac dysfunction may precede vascular dysfunction in such patients. When interpreting the relationship between baPWV and LV diastolic function, the rbPEP/rbET value obtained from the same examination should be considered.

  15. Scintigraphical analyses of pulmonary function in dogs

    International Nuclear Information System (INIS)

    Clercx, C.

    1988-01-01

    The main goal of this study was to develop a quantitative analysis from 99mTc aerosol inhalation/perfusion (I/P) lung scintigrams. In particular attention was focused on both the regional I/P distribution, concerning the ratio of the mean I and P values in several lung regions, as well as on the local (intraregional) distribution of I/P, under a wide range of circumstances. In Ch. 2, the method and reference material are described. The distribution of the inhalation-to-perfusion ratios (I/P) is studied in anesthetized healthy dogs, with emphasis on inter-regional distribution and intra-regional dispersion of the I/P ratio. Moreover, it provides an insight into canine pulmonary physiology, frequently transposed from human lung physiology, what is not always correct. Ch. 3 deals with the possible methodological and physiological influences on the interpretation of scintigraphical measurements, such as age, posture and breed. Investigation of the effects of age and breed was pursued using qualitative studies of canine lung surfactant. The actual knowledge in this field lets prospect veterinary clinical meaning in the future. Finally in Ch. 4, the diagnostic value of the measurements was examined in experimental models of important lung disorders with different pathophysiological features, such as lobar and sublobar airway obstruction, and lung embolism. It also permits the investigation of the relative contribution of different compensating mechanisms upon the ventilation-to-perfusion ratio, such as collateral ventilation and hypoxic vasoconstriction. 218 refs.; 31 figs.; 14 tabs

  16. Functional analyses of Populus euphratica brassinosteroid biosyn ...

    Indian Academy of Sciences (India)

    2016-09-28

    Sep 28, 2016 ... lengths and seed yields were similar, but in bolting time and stem diameters, they were opposite. .... This study reports the changes of PeDWF4-TL, PeCPD- .... RNA isolation and the first-strand cDNA synthesis were as above.

  17. Defining and Differentiating the Makerspace

    Science.gov (United States)

    Dousay, Tonia A.

    2017-01-01

    Many resources now punctuate the maker movement landscape. However, some schools and communities still struggle to understand this burgeoning movement. How do we define these spaces and differentiate them from previous labs and shops? Through a multidimensional framework, stakeholders should consider how the structure, access, staffing, and tools…

  18. Indico CONFERENCE: Define the Programme

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial you are going to learn how to define the programme of a conference in Indico. The program of your conference is divided in different “tracks”. Tracks represent the subject matter of the conference, such as “Online Computing”, “Offline Computing”, and so on.

  19. Seismic fragility analyses

    International Nuclear Information System (INIS)

    Kostov, Marin

    2000-01-01

    In the last two decades there is increasing number of probabilistic seismic risk assessments performed. The basic ideas of the procedure for performing a Probabilistic Safety Analysis (PSA) of critical structures (NUREG/CR-2300, 1983) could be used also for normal industrial and residential buildings, dams or other structures. The general formulation of the risk assessment procedure applied in this investigation is presented in Franzini, et al., 1984. The probability of failure of a structure for an expected lifetime (for example 50 years) can be obtained from the annual frequency of failure, β E determined by the relation: β E ∫[d[β(x)]/dx]P(flx)dx. β(x) is the annual frequency of exceedance of load level x (for example, the variable x may be peak ground acceleration), P(fI x) is the conditional probability of structure failure at a given seismic load level x. The problem leads to the assessment of the seismic hazard β(x) and the fragility P(fl x). The seismic hazard curves are obtained by the probabilistic seismic hazard analysis. The fragility curves are obtained after the response of the structure is defined as probabilistic and its capacity and the associated uncertainties are assessed. Finally the fragility curves are combined with the seismic loading to estimate the frequency of failure for each critical scenario. The frequency of failure due to seismic event is presented by the scenario with the highest frequency. The tools usually applied for probabilistic safety analyses of critical structures could relatively easily be adopted to ordinary structures. The key problems are the seismic hazard definitions and the fragility analyses. The fragility could be derived either based on scaling procedures or on the base of generation. Both approaches have been presented in the paper. After the seismic risk (in terms of failure probability) is assessed there are several approaches for risk reduction. Generally the methods could be classified in two groups. The

  20. Microcomputer-controlled thermoluminescent analyser IJS MR-200

    International Nuclear Information System (INIS)

    Mihelic, M.; Miklavzic, U.; Rupnik, Z.; Satalic, P.; Spreizer, F.; Zerovnik, I.

    1985-01-01

    Performances and concept of the multipurpose, microcomputer-controlled thermoluminescent analyser, designed for use in laboratory work TL dosemeters as well as for routine dose readings in the range from ecological to accident doses is described. The main features of the analyser are: time-linear sampling, digitalisation, storing, and subsequent displaying on the monitor time scale of the glow and and temperature curve of the TL material; digital stabilization, control and diagnostic of the analog unit; ability of storing 7 different 8-parametric heating programs; ability of storing 15 evaluation programs defined by 2 or 4 parameters and 3 different algorithms (altogether 5 types of evaluations). Analyser has several features intended for routine work: 9 function keys and possibilities of file forming on cassette or display disc, of dose calculation and averaging, of printing reports with names, and possibility of additional programming in Basic. (author)

  1. Binary analysis: 1. part: definitions and treatment of binary functions; 2. part: applications and functions of trans-coding; Analyse binaire: 1ere partie: definitions et traitements des fonctions binaires; 2eme partie: applications et fonctions de transcodage

    Energy Technology Data Exchange (ETDEWEB)

    Vallee, R L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1968-07-01

    The study of binary groups under their mathematical aspects constitutes the matter of binary analysis, the purpose of which consists in developing altogether simple, rigorous and practical methods needed by the technicians, the engineers and all those who may be mainly concerned by digital processing. This subject, fast extending if not determining, however tends actually to play a main part in nuclear electronics as well as in several other research areas. (authors) [French] L'analyse binaire a pour objet l'etude mathematique des proprietes d'ensembles binaires algebriques et pour but l'elaboration de methodes simples, rigoureuses et pratiques, destinees aux techniciens, aux ingenieurs et a tous ceux qu'interesse directement le traitement numerique de l'information, discipline en expansion rapide qui, deja, en electronique nucleaire comme dans de nombreux autres domaines de la recherche, tend a jouer un role essentiel sinon determinant. (auteurs)

  2. X marks the spot : structural and functional brain mapping in a genetically defined group at high risk of autism symptoms (47,XXY), and a comparison with idiopathic autism spectrum disorder

    NARCIS (Netherlands)

    Goddard, Marcia Naomi

    2015-01-01

    Klinefelter syndrome (47,XXY) is associated with a wide range of behavioral problems, including autism symptomatology. In the current thesis, brain structure and function were assesed in boys with 47,XXY, boys with idiopathic autism spectrum disorder, and non-clinical controls, using multiple

  3. AIDS defining disease: Disseminated cryptococcosis

    Directory of Open Access Journals (Sweden)

    Roshan Anupama

    2006-01-01

    Full Text Available Disseminated cryptococcosis is one of the acquired immune deficiency syndrome defining criteria and the most common cause of life threatening meningitis. Disseminated lesions in the skin manifest as papules or nodules that mimic molluscum contagiosum (MC. We report here a human immunodeficiency virus positive patient who presented with MC like lesions. Disseminated cryptococcosis was confirmed by India ink preparation and histopathology. The condition of the patient improved with amphotercin B.

  4. How do people define moderation?

    Science.gov (United States)

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin

    2015-01-01

    . To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P... and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent...

  6. The World Health Organisation Disability Assessment Scale (WHODAS II: Links between self-rated health and objectively defined and clinical parameters in the population of spinal cord injury

    Directory of Open Access Journals (Sweden)

    Steinerte V.

    2016-01-01

    Full Text Available There are many clinical and objectively defined parameters that are used to evaluate a person's disability. Since the World Health Organisation has presented the WHODAS II as a means of objectively measuring subjectively defined functions, greater attention has been focused on self-rated health. Only a few studies, however, have been conducted about differences between self-rated health and objectively defined parameters. The survey for this study was conducted on the basis of WHODAS II and the population in Latvia with spinal cord injury. Respondents were between 18 and 65, and 98 questionnaires were analysed. The results show that people with spinal cord injury on average rate their functioning as limited (33–40 points of 100. Most respondents have been declared to be disabled, which is defined as very serious or severe functional disorders. More than 40% have paid jobs, while one-third do not work for reasons of health. The research shows that there is a close coherence (p< 0.05 between individual, objectively and clinically defined indicators on the one hand and the aspects of the questionnaire in which physical functioning was an important factor on the other hand. In order to understand the real functional abilities of patients and the individual factors that influence those abilities, it is necessary to define functional self-rated health in addition to objectively defined indicators.

  7. (Re)Defining Salesperson Motivation

    DEFF Research Database (Denmark)

    Khusainova, Rushana; de Jong, Ad; Lee, Nick

    2018-01-01

    The construct of motivation is one of the central themes in selling and sales management research. Yet, to-date no review article exists that surveys the construct (both from an extrinsic and intrinsic motivation context), critically evaluates its current status, examines various key challenges...... apparent from the extant research, and suggests new research opportunities based on a thorough review of past work. The authors explore how motivation is defined, major theories underpinning motivation, how motivation has historically been measured, and key methodologies used over time. In addition......, attention is given to principal drivers and outcomes of salesperson motivation. A summarizing appendix of key articles in salesperson motivation is provided....

  8. Defining Usability of PN Services

    DEFF Research Database (Denmark)

    Nicolajsen, Hanne Westh; Ahola, Titta; Fleury, Alexandre

    In this deliverable usability and user experience are defined in relation to MAGNET Beyond technologies, and it is described how the main MAGNET Beyond concepts can be evaluated through the involvement of users. The concepts include the new "Activity based communication approach" for interacting...... with the MAGNET Beyond system, as well as the core concepts: Personal Network, Personal Network-Federation, Service Discovery, User Profile Management, Personal Network Management, Privacy and Security and Context Awareness. The overall plans for the final usability evaluation are documented based on the present...

  9. Poster: A Software-Defined Multi-Camera Network

    OpenAIRE

    Chen, Po-Yen; Chen, Chien; Selvaraj, Parthiban; Claesen, Luc

    2016-01-01

    The widespread popularity of OpenFlow leads to a significant increase in the number of applications developed in SoftwareDefined Networking (SDN). In this work, we propose the architecture of a Software-Defined Multi-Camera Network consisting of small, flexible, economic, and programmable cameras which combine the functions of the processor, switch, and camera. A Software-Defined Multi-Camera Network can effectively reduce the overall network bandwidth and reduce a large amount of the Capex a...

  10. Software-defined reconfigurable microwave photonics processor.

    Science.gov (United States)

    Pérez, Daniel; Gasulla, Ivana; Capmany, José

    2015-06-01

    We propose, for the first time to our knowledge, a software-defined reconfigurable microwave photonics signal processor architecture that can be integrated on a chip and is capable of performing all the main functionalities by suitable programming of its control signals. The basic configuration is presented and a thorough end-to-end design model derived that accounts for the performance of the overall processor taking into consideration the impact and interdependencies of both its photonic and RF parts. We demonstrate the model versatility by applying it to several relevant application examples.

  11. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

    Science.gov (United States)

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-12-01

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational

  12. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

    International Nuclear Information System (INIS)

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-01-01

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔE AB . Counterpoise-corrected interaction energies ΔE AB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A−B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [E MP2/CBS ] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔE CC-MP , a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔE AB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the

  13. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

    Energy Technology Data Exchange (ETDEWEB)

    Maranzana, Andrea, E-mail: andrea.maranzana@unito.it, E-mail: anna.giordana@hotmail.com, E-mail: vincenzo.barone@sns.it, E-mail: mauro.causa@unina.it, E-mail: mipavone@unina.it; Giordana, Anna, E-mail: andrea.maranzana@unito.it, E-mail: anna.giordana@hotmail.com, E-mail: vincenzo.barone@sns.it, E-mail: mauro.causa@unina.it, E-mail: mipavone@unina.it; Indarto, Antonius, E-mail: antonius.indarto@che.itb.ac.id; Tonachini, Glauco, E-mail: glauco.tonachini@unito.it [Dipartimento di Chimica, Università di Torino, Corso Massimo D’Azeglio 48, I-10125 Torino (Italy); Barone, Vincenzo, E-mail: andrea.maranzana@unito.it, E-mail: anna.giordana@hotmail.com, E-mail: vincenzo.barone@sns.it, E-mail: mauro.causa@unina.it, E-mail: mipavone@unina.it [Scuola Normale Superiore, Piazza dei Cavalieri 7, I-56126, Pisa (Italy); Causà, Mauro, E-mail: andrea.maranzana@unito.it, E-mail: anna.giordana@hotmail.com, E-mail: vincenzo.barone@sns.it, E-mail: mauro.causa@unina.it, E-mail: mipavone@unina.it [Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli “Federico II,” Via Cintia, 80126 Napoli (Italy); Pavone, Michele, E-mail: andrea.maranzana@unito.it, E-mail: anna.giordana@hotmail.com, E-mail: vincenzo.barone@sns.it, E-mail: mauro.causa@unina.it, E-mail: mipavone@unina.it [Dipartimento di Scienze Chimiche, Università di Napoli “Federico II,” Complesso Universitario di Monte Sant’Angelo, Via Cintia, I-80126 Napoli (Italy)

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔE{sub AB}. Counterpoise-corrected interaction energies ΔE{sub AB} are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A−B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [E{sub MP2/CBS}] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔE{sub CC-MP}, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔE{sub AB} with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting

  14. Expressiveness and definability in circumscription

    Directory of Open Access Journals (Sweden)

    Francicleber Martins Ferreira

    2011-06-01

    Full Text Available We investigate expressiveness and definability issues with respect to minimal models, particularly in the scope of Circumscription. First, we give a proof of the failure of the Löwenheim-Skolem Theorem for Circumscription. Then we show that, if the class of P; Z-minimal models of a first-order sentence is Δ-elementary, then it is elementary. That is, whenever the circumscription of a first-order sentence is equivalent to a first-order theory, then it is equivalent to a finitely axiomatizable one. This means that classes of models of circumscribed theories are either elementary or not Δ-elementary. Finally, using the previous result, we prove that, whenever a relation Pi is defined in the class of P; Z-minimal models of a first-order sentence Φ and whenever such class of P; Z-minimal models is Δ-elementary, then there is an explicit definition ψ for Pi such that the class of P; Z-minimal models of Φ is the class of models of Φ ∧ ψ. In order words, the circumscription of P in Φ with Z varied can be replaced by Φ plus this explicit definition ψ for Pi.

  15. Defining Quality in Undergraduate Education

    Directory of Open Access Journals (Sweden)

    Alison W. Bowers

    2018-01-01

    Full Text Available Objectives: This research brief explores the literature addressing quality in undergraduate education to identify what previous research has said about quality and to offer future directions for research on quality in undergraduate education. Method: We conducted a scoping review to provide a broad overview of existing research. Using targeted search terms in academic databases, we identified and reviewed relevant academic literature to develop emergent themes and implications for future research. Results: The exploratory review of the literature revealed a range of thoughtful discussions and empirical studies attempting to define quality in undergraduate education. Many publications highlighted the importance of including different stakeholder perspectives and presented some of the varying perceptions of quality among different stakeholders. Conclusions: While a number of researchers have explored and written about how to define quality in undergraduate education, there is not a general consensus regarding a definition of quality in undergraduate education. Past research offers a range of insights, models, and data to inform future research. Implication for Theory and/or Practice: We provide four recommendations for future research to contribute to a high quality undergraduate educational experience. We suggest more comprehensive systematic reviews of the literature as a next step.

  16. Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

    Science.gov (United States)

    Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

    2018-01-01

    Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

  17. Number series of atoms, interatomic bonds and interface bonds defining zinc-blende nanocrystals as function of size, shape and surface orientation: Analytic tools to interpret solid state spectroscopy data

    Directory of Open Access Journals (Sweden)

    Dirk König

    2016-08-01

    Full Text Available Semiconductor nanocrystals (NCs experience stress and charge transfer by embedding materials or ligands and impurity atoms. In return, the environment of NCs experiences a NC stress response which may lead to matrix deformation and propagated strain. Up to now, there is no universal gauge to evaluate the stress impact on NCs and their response as a function of NC size dNC. I deduce geometrical number series as analytical tools to obtain the number of NC atoms NNC(dNC[i], bonds between NC atoms Nbnd(dNC[i] and interface bonds NIF(dNC[i] for seven high symmetry zinc-blende (zb NCs with low-index faceting: {001} cubes, {111} octahedra, {110} dodecahedra, {001}-{111} pyramids, {111} tetrahedra, {111}-{001} quatrodecahedra and {001}-{111} quadrodecahedra. The fundamental insights into NC structures revealed here allow for major advancements in data interpretation and understanding of zb- and diamond-lattice based nanomaterials. The analytical number series can serve as a standard procedure for stress evaluation in solid state spectroscopy due to their deterministic nature, easy use and general applicability over a wide range of spectroscopy methods as well as NC sizes, forms and materials.

  18. Number series of atoms, interatomic bonds and interface bonds defining zinc-blende nanocrystals as function of size, shape and surface orientation: Analytic tools to interpret solid state spectroscopy data

    Energy Technology Data Exchange (ETDEWEB)

    König, Dirk, E-mail: dirk.koenig@unsw.edu.au [Integrated Materials Design Centre (IMDC) and School of Photovoltaic and Renewable Energy Engineering (SPREE), University of New South Wales, Sydney (Australia)

    2016-08-15

    Semiconductor nanocrystals (NCs) experience stress and charge transfer by embedding materials or ligands and impurity atoms. In return, the environment of NCs experiences a NC stress response which may lead to matrix deformation and propagated strain. Up to now, there is no universal gauge to evaluate the stress impact on NCs and their response as a function of NC size d{sub NC}. I deduce geometrical number series as analytical tools to obtain the number of NC atoms N{sub NC}(d{sub NC}[i]), bonds between NC atoms N{sub bnd}(d{sub NC}[i]) and interface bonds N{sub IF}(d{sub NC}[i]) for seven high symmetry zinc-blende (zb) NCs with low-index faceting: {001} cubes, {111} octahedra, {110} dodecahedra, {001}-{111} pyramids, {111} tetrahedra, {111}-{001} quatrodecahedra and {001}-{111} quadrodecahedra. The fundamental insights into NC structures revealed here allow for major advancements in data interpretation and understanding of zb- and diamond-lattice based nanomaterials. The analytical number series can serve as a standard procedure for stress evaluation in solid state spectroscopy due to their deterministic nature, easy use and general applicability over a wide range of spectroscopy methods as well as NC sizes, forms and materials.

  19. Defining the "normal" postejaculate urinalysis.

    Science.gov (United States)

    Mehta, Akanksha; Jarow, Jonathan P; Maples, Pat; Sigman, Mark

    2012-01-01

    Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 ± 1.6 vs 2.0 ± 1.4 mL, P sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (sperm counts in PEU (sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management.

  20. Miniature EVA Software Defined Radio

    Science.gov (United States)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  1. Space shuttle orbiter guidance, naviagation and control software functional requirements: Horizontal flight operations

    Science.gov (United States)

    1972-01-01

    The shuttle GN&C software functions for horizontal flight operations are defined. Software functional requirements are grouped into two categories: first horizontal flight requirements and full mission horizontal flight requirements. The document privides the intial step in the shuttle GN&C software design process. It also serves as a management tool to identify analyses which are required to define requirements.

  2. Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli.

    Science.gov (United States)

    Jovanovic, Goran; Mehta, Parul; Ying, Liming; Buck, Martin

    2014-11-01

    All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipin-rich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization. © 2014 The Authors.

  3. Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome

    Directory of Open Access Journals (Sweden)

    Olatz Villate

    2018-01-01

    Full Text Available Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

  4. Expressional and functional analyses of transcription factors activated by BMP-4s signaling in early xenopus embryo; BMP-4 shigunaru dentatsu kiko to sono hyoteki kakunai tensha inshi ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Maeno, Mitsugu [Niigata University, Niigata (Japan). Faculty of Science

    1998-12-16

    The expression and physiological function of two transcription factors, GATA-2 and Xmsx-1, in amphibian embryos has been analyzed. The expression of these mRNAs in embryonic cells were firmly regulated by the BMP-4 signaling, that plays a central role in the formation of ventral tissues. The microinjection studies of GATA-2 RNA into embryonic cells suggested that this factor functions in two adjacent germ layers, mesoderm and ectoderm, to participate in blood cell formation in ventral area of embryo. Embryos injected with Xmsx-1 RNA, but not with GATA-2, in dorsal blastomeres exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Thus, Xmsx-1 is a ventralizing agent. However, on the basis of molecular marker analyses, Xmsx-1 did not promote erythropoietic differentiation, but promoted muscle tissue formation. It has been concluded that Xmsx-1 si a target transcription factor of the BMP-4 signaling, but possesses a distinct activity on dorso-ventral patterning of mesodermal tissues. (author)

  5. Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome.

    Science.gov (United States)

    Villate, Olatz; Ibarluzea, Nekane; Fraile-Bethencourt, Eugenia; Valenzuela, Alberto; Velasco, Eladio A; Grozeva, Detelina; Raymond, F L; Botella, María P; Tejada, María-Isabel

    2018-01-01

    Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS) of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T) was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD ® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG) 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

  6. Secondary mediation and regression analyses of the PTClinResNet database: determining causal relationships among the International Classification of Functioning, Disability and Health levels for four physical therapy intervention trials.

    Science.gov (United States)

    Mulroy, Sara J; Winstein, Carolee J; Kulig, Kornelia; Beneck, George J; Fowler, Eileen G; DeMuth, Sharon K; Sullivan, Katherine J; Brown, David A; Lane, Christianne J

    2011-12-01

    Each of the 4 randomized clinical trials (RCTs) hosted by the Physical Therapy Clinical Research Network (PTClinResNet) targeted a different disability group (low back disorder in the Muscle-Specific Strength Training Effectiveness After Lumbar Microdiskectomy [MUSSEL] trial, chronic spinal cord injury in the Strengthening and Optimal Movements for Painful Shoulders in Chronic Spinal Cord Injury [STOMPS] trial, adult stroke in the Strength Training Effectiveness Post-Stroke [STEPS] trial, and pediatric cerebral palsy in the Pediatric Endurance and Limb Strengthening [PEDALS] trial for children with spastic diplegic cerebral palsy) and tested the effectiveness of a muscle-specific or functional activity-based intervention on primary outcomes that captured pain (STOMPS, MUSSEL) or locomotor function (STEPS, PEDALS). The focus of these secondary analyses was to determine causal relationships among outcomes across levels of the International Classification of Functioning, Disability and Health (ICF) framework for the 4 RCTs. With the database from PTClinResNet, we used 2 separate secondary statistical approaches-mediation analysis for the MUSSEL and STOMPS trials and regression analysis for the STEPS and PEDALS trials-to test relationships among muscle performance, primary outcomes (pain related and locomotor related), activity and participation measures, and overall quality of life. Predictive models were stronger for the 2 studies with pain-related primary outcomes. Change in muscle performance mediated or predicted reductions in pain for the MUSSEL and STOMPS trials and, to some extent, walking speed for the STEPS trial. Changes in primary outcome variables were significantly related to changes in activity and participation variables for all 4 trials. Improvement in activity and participation outcomes mediated or predicted increases in overall quality of life for the 3 trials with adult populations. Variables included in the statistical models were limited to those

  7. Use of N stable isotope and microbial analyses to define wastewater influence in Mobile Bay, AL

    Energy Technology Data Exchange (ETDEWEB)

    Daskin, Joshua H. [MB 0193 Brandeis University, Waltham, MA 02454 (United States); Calci, Kevin R.; Burkhardt, William [1 Iberville Road, US Food and Drug Administration Gulf Coast Seafood Laboratory, Dauphin Island, AL 36528 (United States); Carmichael, Ruth H. [101 Bienville Boulevard, Dauphin Island Sea Lab, Dauphin Island, AL 36528 (United States); University of South Alabama, Mobile, AL, 36688 (United States)], E-mail: rcarmichael@disl.org

    2008-05-15

    We assessed short-term ecological and potential human health effects of wastewater treatment plant (WTP) effluent by measuring {delta}{sup 15}N per mille and microbial concentrations in oysters and suspended particulate matter (SPM). We also tested male-specific bacteriophage (MSB) as an alternative to fecal coliforms, to assess potential influence of wastewater contamination on shellfish. WTP effluent did not affect oyster growth or survival, but SPM and oysters acquired wastewater-specific {delta}{sup 15}N per mille . {delta}{sup 15}N values were depleted near the WTP, typical of low-level processed wastewater. Fecal coliform and MSB concentrations were higher in samples taken closest to the WTP, and MSB values were significantly correlated with {delta}{sup 15}N per mille in oyster tissues. Overall, oysters demonstrated relatively rapid integration and accumulation of wastewater-specific {delta}{sup 15}N per mille and indicator microorganisms compared to water samples. These data suggest oysters were superior sentinels compared to water, and MSB was a more reliable indicator of wastewater influence on shellfish than fecal coliforms.

  8. Use of N stable isotope and microbial analyses to define wastewater influence in Mobile Bay, AL

    International Nuclear Information System (INIS)

    Daskin, Joshua H.; Calci, Kevin R.; Burkhardt, William; Carmichael, Ruth H.

    2008-01-01

    We assessed short-term ecological and potential human health effects of wastewater treatment plant (WTP) effluent by measuring δ 15 N per mille and microbial concentrations in oysters and suspended particulate matter (SPM). We also tested male-specific bacteriophage (MSB) as an alternative to fecal coliforms, to assess potential influence of wastewater contamination on shellfish. WTP effluent did not affect oyster growth or survival, but SPM and oysters acquired wastewater-specific δ 15 N per mille . δ 15 N values were depleted near the WTP, typical of low-level processed wastewater. Fecal coliform and MSB concentrations were higher in samples taken closest to the WTP, and MSB values were significantly correlated with δ 15 N per mille in oyster tissues. Overall, oysters demonstrated relatively rapid integration and accumulation of wastewater-specific δ 15 N per mille and indicator microorganisms compared to water samples. These data suggest oysters were superior sentinels compared to water, and MSB was a more reliable indicator of wastewater influence on shellfish than fecal coliforms

  9. Use of N stable isotope and microbial analyses to define wastewater influence in Mobile Bay, AL.

    Science.gov (United States)

    Daskin, Joshua H; Calci, Kevin R; Burkhardt, William; Carmichael, Ruth H

    2008-05-01

    We assessed short-term ecological and potential human health effects of wastewater treatment plant (WTP) effluent by measuring delta 15N per thousand and microbial concentrations in oysters and suspended particulate matter (SPM). We also tested male-specific bacteriophage (MSB) as an alternative to fecal coliforms, to assess potential influence of wastewater contamination on shellfish. WTP effluent did not affect oyster growth or survival, but SPM and oysters acquired wastewater-specific delta 15N per thousand. delta 15N values were depleted near the WTP, typical of low-level processed wastewater. Fecal coliform and MSB concentrations were higher in samples taken closest to the WTP, and MSB values were significantly correlated with delta 15N per thousand in oyster tissues. Overall, oysters demonstrated relatively rapid integration and accumulation of wastewater-specific delta 15N per thousand and indicator microorganisms compared to water samples. These data suggest oysters were superior sentinels compared to water, and MSB was a more reliable indicator of wastewater influence on shellfish than fecal coliforms.

  10. Set Theory Applied to Uniquely Define the Inputs to Territorial Systems in Emergy Analyses

    Science.gov (United States)

    The language of set theory can be utilized to represent the emergy involved in all processes. In this paper we use set theory in an emergy evaluation to ensure an accurate representation of the inputs to territorial systems. We consider a generic territorial system and we describ...

  11. The benefits of defining "snacks".

    Science.gov (United States)

    Hess, Julie M; Slavin, Joanne L

    2018-04-18

    Whether eating a "snack" is considered a beneficial or detrimental behavior is largely based on how "snack" is defined. The term "snack food" tends to connote energy-dense, nutrient-poor foods high in nutrients to limit (sugar, sodium, and/or saturated fat) like cakes, cookies, chips and other salty snacks, and sugar-sweetened beverages. Eating a "snack food" is often conflated with eating a "snack," however, leading to an overall perception of snacks as a dietary negative. Yet the term "snack" can also refer simply to an eating occasion outside of breakfast, lunch, or dinner. With this definition, the evidence to support health benefits or detriments to eating a "snack" remains unclear, in part because relatively few well-designed studies that specifically focus on the impact of eating frequency on health have been conducted. Despite these inconsistencies and research gaps, in much of the nutrition literature, "snacking" is still referred to as detrimental to health. As discussed in this review, however, there are multiple factors that influence the health impacts of snacking, including the definition of "snack" itself, the motivation to snack, body mass index of snack eaters, and the food selected as a snack. Without a definition of "snack" and a body of research using methodologically rigorous protocols, determining the health impact of eating a "snack" will continue to elude the nutrition research community and prevent the development of evidence-based policies about snacking that support public health. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Defining Tobacco Regulatory Science Competencies.

    Science.gov (United States)

    Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

    2017-02-01

    In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

    2017-01-01

    Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

  14. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  15. Numerical analysis on pool boiling using user defined function

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Sung Uk; Jeon, Byong Guk; Kim, Seok; Euh, Dong-Jin [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    PAFS (passive auxiliary feedwater system) adopted in the APR+ (Advanced Power Reactor Plus) of Korea is one such application. When PAFS is activated with an actuation signal, steam from the steam generator passes through heat exchanger tubes submerged in a water tank of the PAFS. Outside these heat exchanger tubes, nucleate boiling phenomena appears. In the present work, a numerical study is reported on three-dimensional transient state pool boiling of water having an immersed heat source. The velocity vector fields during the decrease in the water level are numerically investigated in a pool, and the accuracy of the results is checked by comparing the experimental results conducted using the PIV techniques by Kim et al. These numerical results can be used as basic research data for an analysis and prediction of the natural circulation phenomena in the cooling tank of the passive safety system in a nuclear power plant.

  16. Defining functional classes of Barth syndrome mutation in humans

    NARCIS (Netherlands)

    Lu, Ya-Wen; Galbraith, Laura; Herndon, Jenny D.; Lu, Ya-Lin; Pras-Raves, Mia; Vervaart, Martin; van Kampen, Antoine; Luyf, Angela; Koehler, Carla M.; McCaffery, J. Michael; Gottlieb, Eyal; Vaz, Frederic M.; Claypool, Steven M.

    2016-01-01

    The X-linked disease Barth syndrome (BTHS) is caused by mutations in TAZ; TAZ is the main determinant of the final acyl chain composition of the mitochondrial-specific phospholipid, cardiolipin. To date, a detailed characterization of endogenous TAZ has only been performed in yeast. Further, why a

  17. Defining function in rangelands of the Peddie district, Eastern Cape ...

    African Journals Online (AJOL)

    Following the analysis of satellite-derived vegetation indices, the commercial site had higher active green biomass (higher NDVI) and lower spatial diversity of near-infra red band (lower MSDI) than the communal site. Keywords: soil surface assessment; nutrient content; degradation; fenceline contrasts; patches; fetches

  18. Estimating Functions of Distributions Defined over Spaces of Unknown Size

    Directory of Open Access Journals (Sweden)

    David H. Wolpert

    2013-10-01

    Full Text Available We consider Bayesian estimation of information-theoretic quantities from data, using a Dirichlet prior. Acknowledging the uncertainty of the event space size m and the Dirichlet prior’s concentration parameter c, we treat both as random variables set by a hyperprior. We show that the associated hyperprior, P(c, m, obeys a simple “Irrelevance of Unseen Variables” (IUV desideratum iff P(c, m = P(cP(m. Thus, requiring IUV greatly reduces the number of degrees of freedom of the hyperprior. Some information-theoretic quantities can be expressed multiple ways, in terms of different event spaces, e.g., mutual information. With all hyperpriors (implicitly used in earlier work, different choices of this event space lead to different posterior expected values of these information-theoretic quantities. We show that there is no such dependence on the choice of event space for a hyperprior that obeys IUV. We also derive a result that allows us to exploit IUV to greatly simplify calculations, like the posterior expected mutual information or posterior expected multi-information. We also use computer experiments to favorably compare an IUV-based estimator of entropy to three alternative methods in common use. We end by discussing how seemingly innocuous changes to the formalization of an estimation problem can substantially affect the resultant estimates of posterior expectations.

  19. Reconfigurable, Cognitive Software-Defined Radio

    Science.gov (United States)

    Bhat, Arvind

    2015-01-01

    Software-defined radio (SDR) technology allows radios to be reconfigured to perform different communication functions without using multiple radios to accomplish each task. Intelligent Automation, Inc., has developed SDR platforms that switch adaptively between different operation modes. The innovation works by modifying both transmit waveforms and receiver signal processing tasks. In Phase I of the project, the company developed SDR cognitive capabilities, including adaptive modulation and coding (AMC), automatic modulation recognition (AMR), and spectrum sensing. In Phase II, these capabilities were integrated into SDR platforms. The reconfigurable transceiver design employs high-speed field-programmable gate arrays, enabling multimode operation and scalable architecture. Designs are based on commercial off-the-shelf (COTS) components and are modular in nature, making it easier to upgrade individual components rather than redesigning the entire SDR platform as technology advances.

  20. UMTS signal measurements with digital spectrum analysers

    International Nuclear Information System (INIS)

    Licitra, G.; Palazzuoli, D.; Ricci, A. S.; Silvi, A. M.

    2004-01-01

    The launch of the Universal Mobile Telecommunications System (UNITS), the most recent mobile telecommunications standard has imposed the requirement of updating measurement instrumentation and methodologies. In order to define the most reliable measurement procedure, which is aimed at assessing the exposure to electromagnetic fields, modern spectrum analysers' features for correct signal characterisation has been reviewed. (authors)

  1. Defining a Cancer Dependency Map.

    Science.gov (United States)

    Tsherniak, Aviad; Vazquez, Francisca; Montgomery, Phil G; Weir, Barbara A; Kryukov, Gregory; Cowley, Glenn S; Gill, Stanley; Harrington, William F; Pantel, Sasha; Krill-Burger, John M; Meyers, Robin M; Ali, Levi; Goodale, Amy; Lee, Yenarae; Jiang, Guozhi; Hsiao, Jessica; Gerath, William F J; Howell, Sara; Merkel, Erin; Ghandi, Mahmoud; Garraway, Levi A; Root, David E; Golub, Todd R; Boehm, Jesse S; Hahn, William C

    2017-07-27

    Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on- from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features. Many dependencies fall into a limited number of classes, and unexpectedly, in 82% of models, the top biomarkers were expression based. We demonstrated the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC. Together, these observations provide a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The problem of defining myth

    Directory of Open Access Journals (Sweden)

    Lauri Honko

    1972-01-01

    Full Text Available The first thing that one realises in trying to grasp the semantic implications of myth is that myth can cover an extremely wide field. The way in which the term myth is commonly used reveals, too, that the word is loaded with emotional overtones. These overtones creep not only into common parlance but also, somewhat surprisingly, into scientific usage. That myth does, in fact, carry emotional overtones in this way is perhaps most easily seen if we think of terms such as prayer, liturgy, ritual drama, spell: they are all used for different religious genres but would seem to be more neutral than myth. It appears to be difficult for many scholars to discuss myth simply as a form of religious communication, as one genre among other genres. If one differentiates between four levels, namely, form, content, function and context, it is much easier to encounter the varied uses which the concept has acquired in scientific literature. By this it is possible to delimit and yet be flexible at the same time. There is no need to welcome with open arms just any traditions into the fold of myth research: but nor is it necessary to exclude, for example, studies of myth where the context criterion, i.e. a context of ritual, is not fulfilled. The degree of flexibility that can be achieved is dependent on the approach that the scholar has chosen.

  3. Laser Beam Focus Analyser

    DEFF Research Database (Denmark)

    Nielsen, Peter Carøe; Hansen, Hans Nørgaard; Olsen, Flemming Ove

    2007-01-01

    the obtainable features in direct laser machining as well as heat affected zones in welding processes. This paper describes the development of a measuring unit capable of analysing beam shape and diameter of lasers to be used in manufacturing processes. The analyser is based on the principle of a rotating......The quantitative and qualitative description of laser beam characteristics is important for process implementation and optimisation. In particular, a need for quantitative characterisation of beam diameter was identified when using fibre lasers for micro manufacturing. Here the beam diameter limits...... mechanical wire being swept through the laser beam at varying Z-heights. The reflected signal is analysed and the resulting beam profile determined. The development comprised the design of a flexible fixture capable of providing both rotation and Z-axis movement, control software including data capture...

  4. Analysing and Comparing Encodability Criteria

    Directory of Open Access Journals (Sweden)

    Kirstin Peters

    2015-08-01

    Full Text Available Encodings or the proof of their absence are the main way to compare process calculi. To analyse the quality of encodings and to rule out trivial or meaningless encodings, they are augmented with quality criteria. There exists a bunch of different criteria and different variants of criteria in order to reason in different settings. This leads to incomparable results. Moreover it is not always clear whether the criteria used to obtain a result in a particular setting do indeed fit to this setting. We show how to formally reason about and compare encodability criteria by mapping them on requirements on a relation between source and target terms that is induced by the encoding function. In particular we analyse the common criteria full abstraction, operational correspondence, divergence reflection, success sensitiveness, and respect of barbs; e.g. we analyse the exact nature of the simulation relation (coupled simulation versus bisimulation that is induced by different variants of operational correspondence. This way we reduce the problem of analysing or comparing encodability criteria to the better understood problem of comparing relations on processes.

  5. Contesting Citizenship: Comparative Analyses

    DEFF Research Database (Denmark)

    Siim, Birte; Squires, Judith

    2007-01-01

    importance of particularized experiences and multiple ineequality agendas). These developments shape the way citizenship is both practiced and analysed. Mapping neat citizenship modles onto distinct nation-states and evaluating these in relation to formal equality is no longer an adequate approach....... Comparative citizenship analyses need to be considered in relation to multipleinequalities and their intersections and to multiple governance and trans-national organisinf. This, in turn, suggests that comparative citizenship analysis needs to consider new spaces in which struggles for equal citizenship occur...