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Sample records for gene smed-prep defines

  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. 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.

  3. Patterns of gene flow define species of thermophilic Archaea.

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    Hinsby Cadillo-Quiroz

    2012-02-01

    Full Text Available Despite a growing appreciation of their vast diversity in nature, mechanisms of speciation are poorly understood in Bacteria and Archaea. Here we use high-throughput genome sequencing to identify ongoing speciation in the thermoacidophilic Archaeon Sulfolobus islandicus. Patterns of homologous gene flow among genomes of 12 strains from a single hot spring in Kamchatka, Russia, demonstrate higher levels of gene flow within than between two persistent, coexisting groups, demonstrating that these microorganisms fit the biological species concept. Furthermore, rates of gene flow between two species are decreasing over time in a manner consistent with incipient speciation. Unlike other microorganisms investigated, we do not observe a relationship between genetic divergence and frequency of recombination along a chromosome, or other physical mechanisms that would reduce gene flow between lineages. Each species has its own genetic island encoding unique physiological functions and a unique growth phenotype that may be indicative of ecological specialization. Genetic differentiation between these coexisting groups occurs in large genomic "continents," indicating the topology of genomic divergence during speciation is not uniform and is not associated with a single locus under strong diversifying selection. These data support a model where species do not require physical barriers to gene flow but are maintained by ecological differentiation.

  4. Patterns of gene flow define species of thermophilic Archaea.

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    Cadillo-Quiroz, Hinsby; Didelot, Xavier; Held, Nicole L; Herrera, Alfa; Darling, Aaron; Reno, Michael L; Krause, David J; Whitaker, Rachel J

    2012-02-01

    Despite a growing appreciation of their vast diversity in nature, mechanisms of speciation are poorly understood in Bacteria and Archaea. Here we use high-throughput genome sequencing to identify ongoing speciation in the thermoacidophilic Archaeon Sulfolobus islandicus. Patterns of homologous gene flow among genomes of 12 strains from a single hot spring in Kamchatka, Russia, demonstrate higher levels of gene flow within than between two persistent, coexisting groups, demonstrating that these microorganisms fit the biological species concept. Furthermore, rates of gene flow between two species are decreasing over time in a manner consistent with incipient speciation. Unlike other microorganisms investigated, we do not observe a relationship between genetic divergence and frequency of recombination along a chromosome, or other physical mechanisms that would reduce gene flow between lineages. Each species has its own genetic island encoding unique physiological functions and a unique growth phenotype that may be indicative of ecological specialization. Genetic differentiation between these coexisting groups occurs in large genomic "continents," indicating the topology of genomic divergence during speciation is not uniform and is not associated with a single locus under strong diversifying selection. These data support a model where species do not require physical barriers to gene flow but are maintained by ecological differentiation.

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

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    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.

  6. Defining genes using "blueprint" versus "instruction" metaphors: effects for genetic determinism, response efficacy, and perceived control.

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    Parrott, Roxanne; Smith, Rachel A

    2014-01-01

    Evidence supports mixed attributions aligned with personal and/or clinical control and gene expression for health in this era of genomic science and health care. We consider variance in these attributions and possible relationships to individual mind sets associated with essentialist beliefs that genes determine health versus threat beliefs that genes increase susceptibility for disease and severity linked to gene-environment interactions. Further, we contribute to theory and empirical research to evaluate the use of metaphors to define genes. Participants (N = 324) read a message that varied the introduction by providing a definition of genes that used either an "instruction" metaphor or a "blueprint" metaphor. The "instruction" metaphor compared to the "blueprint" metaphor promoted stronger threat perceptions, which aligned with both belief in the response efficacy of genetic research for health and perceived behavioral control linked to genes and health. The "blueprint" metaphor compared to the "instruction" metaphor promoted stronger essentialist beliefs, which aligned with more intense positive regard for the efficacy of genetic research and human health. Implications for health communicators include societal effects aligned with stigma and discrimination that such findings portend.

  7. Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.

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    Lindgren, David; Eriksson, Pontus; Krawczyk, Krzysztof; Nilsson, Helén; Hansson, Jennifer; Veerla, Srinivas; Sjölund, Jonas; Höglund, Mattias; Johansson, Martin E; Axelson, Håkan

    2017-08-08

    Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression.

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    Christian J Gröger

    Full Text Available The epithelial to mesenchymal transition (EMT represents a crucial event during cancer progression and dissemination. EMT is the conversion of carcinoma cells from an epithelial to a mesenchymal phenotype that associates with a higher cell motility as well as enhanced chemoresistance and cancer stemness. Notably, EMT has been increasingly recognized as an early event of metastasis. Numerous gene expression studies (GES have been conducted to obtain transcriptome signatures and marker genes to understand the regulatory mechanisms underlying EMT. Yet, no meta-analysis considering the multitude of GES of EMT has been performed to comprehensively elaborate the core genes in this process. Here we report the meta-analysis of 18 independent and published GES of EMT which focused on different cell types and treatment modalities. Computational analysis revealed clustering of GES according to the type of treatment rather than to cell type. GES of EMT induced via transforming growth factor-β and tumor necrosis factor-α treatment yielded uniformly defined clusters while GES of models with alternative EMT induction clustered in a more complex fashion. In addition, we identified those up- and downregulated genes which were shared between the multitude of GES. This core gene list includes well known EMT markers as well as novel genes so far not described in this process. Furthermore, several genes of the EMT-core gene list significantly correlated with impaired pathological complete response in breast cancer patients. In conclusion, this meta-analysis provides a comprehensive survey of available EMT expression signatures and shows fundamental insights into the mechanisms that are governing carcinoma progression.

  9. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans

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    York, Dan; Higgins, Robert J.; LeCouteur, Richard A.; Joshi, Nikhil; Bannasch, Danika

    2016-01-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. PMID:27251041

  10. Blood-informative transcripts define nine common axes of peripheral blood gene expression.

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    Marcela Preininger

    Full Text Available We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs, generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

  11. Blood-informative transcripts define nine common axes of peripheral blood gene expression.

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    Preininger, Marcela; Arafat, Dalia; Kim, Jinhee; Nath, Artika P; Idaghdour, Youssef; Brigham, Kenneth L; Gibson, Greg

    2013-01-01

    We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs), generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

  12. The Evolution of Gene Regulatory Networks that Define Arthropod Body Plans.

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    Auman, Tzach; Chipman, Ariel D

    2017-09-01

    Our understanding of the genetics of arthropod body plan development originally stems from work on Drosophila melanogaster from the late 1970s and onward. In Drosophila, there is a relatively detailed model for the network of gene interactions that proceeds in a sequential-hierarchical fashion to define the main features of the body plan. Over the years, we have a growing understanding of the networks involved in defining the body plan in an increasing number of arthropod species. It is now becoming possible to tease out the conserved aspects of these networks and to try to reconstruct their evolution. In this contribution, we focus on several key nodes of these networks, starting from early patterning in which the main axes are determined and the broad morphological domains of the embryo are defined, and on to later stage wherein the growth zone network is active in sequential addition of posterior segments. The pattern of conservation of networks is very patchy, with some key aspects being highly conserved in all arthropods and others being very labile. Many aspects of early axis patterning are highly conserved, as are some aspects of sequential segment generation. In contrast, regional patterning varies among different taxa, and some networks, such as the terminal patterning network, are only found in a limited range of taxa. The growth zone segmentation network is ancient and is probably plesiomorphic to all arthropods. In some insects, it has undergone significant modification to give rise to a more hardwired network that generates individual segments separately. In other insects and in most arthropods, the sequential segmentation network has undergone a significant amount of systems drift, wherein many of the genes have changed. However, it maintains a conserved underlying logic and function. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please

  13. ADAGE signature analysis: differential expression analysis with data-defined gene sets.

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    Tan, Jie; Huyck, Matthew; Hu, Dongbo; Zelaya, René A; Hogan, Deborah A; Greene, Casey S

    2017-11-22

    ADAGE signature analysis to perform gene set analysis using data-defined functional gene signatures. This approach addresses an important gap for biologists studying non-traditional model organisms and those without extensive curated resources available. We built both an R package and web server to provide ADAGE signature analysis to the community.

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

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    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.

  15. Defining the expression of marker genes in equine mesenchymal stromal cells

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    Deborah J Guest

    2008-11-01

    Full Text Available Deborah J Guest1, Jennifer C Ousey1, Matthew RW Smith21Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU; 2Reynolds House Referrals, Greenwood Ellis and Partners, 166 High Street, Newmarket, Suffolk, CB8 9WS, UKAbstract: Mesenchymal stromal (MS cells have been derived from multiple sources in the horse including bone marrow, adipose tissue and umbilical cord blood. To date these cells have been investigated for their differentiation potential and are currently being used to treat damage to horse musculoskeletal tissues. However, no work has been done in horse MS cells to examine the expression profile of proteins and cell surface antigens that are expressed in human MS cells. The identification of such profiles in the horse will allow the comparison of putative MS cells isolated from different laboratories and different tissues. At present it is difficult to ascertain whether equivalent cells are being used in different reports. Here, we report on the expression of a range of markers used to define human MS cells. Using immunocytochemistry we show that horse MS cells homogenously express collagens, alkaline phosphatase activity, CD44, CD90 and CD29. In contrast, CD14, CD79α and the embryonic stem cell markers Oct-4, SSEA (stage specific embryonic antigen -1, -3, -4, TRA (tumor rejection antigen -1–60 and -1–81 are not expressed. The MS cells also express MHC class I antigens but do not express class II antigens, although they are inducible by treatment with interferon gamma (IFN-γ.Keywords: mesenchymal stem cells, equine, gene expression

  16. Defining a new candidate gene for amelogenesis imperfecta: from molecular genetics to biochemistry.

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    Urzúa, Blanca; Ortega-Pinto, Ana; Morales-Bozo, Irene; Rojas-Alcayaga, Gonzalo; Cifuentes, Víctor

    2011-02-01

    Amelogenesis imperfecta is a group of genetic conditions that affect the structure and clinical appearance of tooth enamel. The types (hypoplastic, hypocalcified, and hypomature) are correlated with defects in different stages of the process of enamel synthesis. Autosomal dominant, recessive, and X-linked types have been previously described. These disorders are considered clinically and genetically heterogeneous in etiology, involving a variety of genes, such as AMELX, ENAM, DLX3, FAM83H, MMP-20, KLK4, and WDR72. The mutations identified within these causal genes explain less than half of all cases of amelogenesis imperfecta. Most of the candidate and causal genes currently identified encode proteins involved in enamel synthesis. We think it is necessary to refocus the search for candidate genes using biochemical processes. This review provides theoretical evidence that the human SLC4A4 gene (sodium bicarbonate cotransporter) may be a new candidate gene.

  17. Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

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    Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

    2009-01-01

    Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

  18. Defining global neuroendocrine gene expression patterns associated with reproductive seasonality in fish.

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    Dapeng Zhang

    Full Text Available BACKGROUND: Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning, sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h typical of the springtime breeding season (May, we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABA(A gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. CONCLUSIONS/SIGNIFICANCE: Using both

  19. Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation.

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    Elizabeth A. Robb

    Full Text Available The chicken coloboma mutation exhibits features similar to human congenital developmental malformations such as ocular coloboma, cleft-palate, dwarfism, and polydactyly. The coloboma-associated region and encoded genes were investigated using advanced genomic, genetic, and gene expression technologies. Initially, the mutation was linked to a 990 kb region encoding 11 genes; the application of the genetic and genomic tools led to a reduction of the linked region to 176 kb and the elimination of 7 genes. Furthermore, bioinformatics analyses of capture array-next generation sequence data identified genetic elements including SNPs, insertions, deletions, gaps, chromosomal rearrangements, and miRNA binding sites within the introgressed causative region relative to the reference genome sequence. Coloboma-specific variants within exons, UTRs, and splice sites were studied for their contribution to the mutant phenotype. Our compiled results suggest three genes for future studies. The three candidate genes, SLC30A5 (a zinc transporter, CENPH (a centromere protein, and CDK7 (a cyclin-dependent kinase, are differentially expressed (compared to normal embryos at stages and in tissues affected by the coloboma mutation. Of these genes, two (SLC30A5 and CENPH are considered high-priority candidate based upon studies in other vertebrate model systems.

  20. Gene networks specific for innate immunity define post-traumatic stress disorder.

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    Breen, M S; Maihofer, A X; Glatt, S J; Tylee, D S; Chandler, S D; Tsuang, M T; Risbrough, V B; Baker, D G; O'Connor, D T; Nievergelt, C M; Woelk, C H

    2015-12-01

    The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD.

  1. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy.

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    Hicks, Debbie; Farsani, Golara Torabi; Laval, Steven; Collins, James; Sarkozy, Anna; Martoni, Elena; Shah, Ashoke; Zou, Yaqun; Koch, Manuel; Bönnemann, Carsten G; Roberts, Mark; Lochmüller, Hanns; Bushby, Kate; Straub, Volker

    2014-05-01

    Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in ∼50% of BM cases no mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER. We conclude that the spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1.

  2. Two differentially regulated Arabidopsis genes define a new branch of the DFR superfamily

    DEFF Research Database (Denmark)

    Østergaard, L; Lauvergeat, V; Naested, H

    2001-01-01

    that, whereas high expression of AtCRL1 in mature seeds declines during subsequent vegetative growth, transcriptional activity from the AtCRL2 promoter increases during vegetative growth. Expression of both genes is restricted to vascular tissue. Based upon their homology to proteins involved in lignin......Two tandem genes were identified on Arabidopsis chromosome II (AtCRL1 and AtCRL2) encoding proteins with homology to members of the dihydroflavonol-4-reductase (DFR) superfamily. The encoded CRL1 and CRL2 proteins share 87% mutual amino acid sequence identity whereas their promoter regions...

  3. CAGE-defined promoter regions of the genes implicated in Rett Syndrome

    DEFF Research Database (Denmark)

    Vitezic, Morana; Bertin, Nicolas; Andersson, Robin

    2014-01-01

    BACKGROUND: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other...... reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers...

  4. Chromosomal alterations detected by comparative genomic hybridization in subgroups of gene expression-defined Burkitt's lymphoma

    NARCIS (Netherlands)

    Salaverria, Itziar; Zettl, Andreas; Bea, Silvia; Hartmann, Elena M.; Dave, Sandeep S.; Wright, George W.; Boerma, Evert-Jan; Kluin, Philip M.; Ott, German; Chan, Wing C.; Weisenburger, Dennis D.; Lopez-Guillermo, Armando; Gascoyne, Randy D.; Delabie, Jan; Rimsza, Lisa M.; Braziel, Rita M.; Jaffe, Elaine S.; Staudt, Louis M.; Mueller-Hermelink, Hans Konrad; Campo, Elias; Rosenwald, Andreas

    Background Burkitt's lymphoma is an aggressive B-cell lymphoma characterized by typical morph 0 logical, immunophenotypic and molecular features. Gene expression profiling provided a molecular signature of Burkitt's lymphoma, but also demonstrated that a subset of aggressive B-cell lymphomas not

  5. Data-driven asthma endotypes defined from blood biomarker and gene expression data.

    Directory of Open Access Journals (Sweden)

    Barbara Jane George

    Full Text Available The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels.

  6. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    NARCIS (Netherlands)

    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  7. Flexibility and symmetry of prokaryotic genome rearrangement reveal lineage-associated core-gene-defined genome organizational frameworks.

    Science.gov (United States)

    Kang, Yu; Gu, Chaohao; Yuan, Lina; Wang, Yue; Zhu, Yanmin; Li, Xinna; Luo, Qibin; Xiao, Jingfa; Jiang, Daquan; Qian, Minping; Ahmed Khan, Aftab; Chen, Fei; Zhang, Zhang; Yu, Jun

    2014-11-25

    The prokaryotic pangenome partitions genes into core and dispensable genes. The order of core genes, albeit assumed to be stable under selection in general, is frequently interrupted by horizontal gene transfer and rearrangement, but how a core-gene-defined genome maintains its stability or flexibility remains to be investigated. Based on data from 30 species, including 425 genomes from six phyla, we grouped core genes into syntenic blocks in the context of a pangenome according to their stability across multiple isolates. A subset of the core genes, often species specific and lineage associated, formed a core-gene-defined genome organizational framework (cGOF). Such cGOFs are either single segmental (one-third of the species analyzed) or multisegmental (the rest). Multisegment cGOFs were further classified into symmetric or asymmetric according to segment orientations toward the origin-terminus axis. The cGOFs in Gram-positive species are exclusively symmetric and often reversible in orientation, as opposed to those of the Gram-negative bacteria, which are all asymmetric and irreversible. Meanwhile, all species showing strong strand-biased gene distribution contain symmetric cGOFs and often specific DnaE (α subunit of DNA polymerase III) isoforms. Furthermore, functional evaluations revealed that cGOF genes are hub associated with regard to cellular activities, and the stability of cGOF provides efficient indexes for scaffold orientation as demonstrated by assembling virtual and empirical genome drafts. cGOFs show species specificity, and the symmetry of multisegmental cGOFs is conserved among taxa and constrained by DNA polymerase-centric strand-biased gene distribution. The definition of species-specific cGOFs provides powerful guidance for genome assembly and other structure-based analysis. Prokaryotic genomes are frequently interrupted by horizontal gene transfer (HGT) and rearrangement. To know whether there is a set of genes not only conserved in position

  8. Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Mai Yamauchi

    Full Text Available PURPOSE: To identify stage I lung adenocarcinoma patients with a poor prognosis who will benefit from adjuvant therapy. PATIENTS AND METHODS: Whole gene expression profiles were obtained at 19 time points over a 48-hour time course from human primary lung epithelial cells that were stimulated with epidermal growth factor (EGF in the presence or absence of a clinically used EGF receptor tyrosine kinase (RTK-specific inhibitor, gefitinib. The data were subjected to a mathematical simulation using the State Space Model (SSM. "Gefitinib-sensitive" genes, the expressional dynamics of which were altered by addition of gefitinib, were identified. A risk scoring model was constructed to classify high- or low-risk patients based on expression signatures of 139 gefitinib-sensitive genes in lung cancer using a training data set of 253 lung adenocarcinomas of North American cohort. The predictive ability of the risk scoring model was examined in independent cohorts of surgical specimens of lung cancer. RESULTS: The risk scoring model enabled the identification of high-risk stage IA and IB cases in another North American cohort for overall survival (OS with a hazard ratio (HR of 7.16 (P = 0.029 and 3.26 (P = 0.0072, respectively. It also enabled the identification of high-risk stage I cases without bronchioalveolar carcinoma (BAC histology in a Japanese cohort for OS and recurrence-free survival (RFS with HRs of 8.79 (P = 0.001 and 3.72 (P = 0.0049, respectively. CONCLUSION: The set of 139 gefitinib-sensitive genes includes many genes known to be involved in biological aspects of cancer phenotypes, but not known to be involved in EGF signaling. The present result strongly re-emphasizes that EGF signaling status in cancer cells underlies an aggressive phenotype of cancer cells, which is useful for the selection of early-stage lung adenocarcinoma patients with a poor prognosis. TRIAL REGISTRATION: The Gene Expression Omnibus (GEO GSE31210.

  9. Msx genes define a population of mural cell precursors required for head blood vessel maturation.

    Science.gov (United States)

    Lopes, Miguel; Goupille, Olivier; Saint Cloment, Cécile; Lallemand, Yvan; Cumano, Ana; Robert, Benoît

    2011-07-01

    Vessels are primarily formed from an inner endothelial layer that is secondarily covered by mural cells, namely vascular smooth muscle cells (VSMCs) in arteries and veins and pericytes in capillaries and veinules. We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells. To unravel the role of Msx genes in vascular development, we have inactivated the two Msx genes specifically in mural cells by combining the Msx1(lacZ), Msx2(lox) and Sm22α-Cre alleles. Optical projection tomography demonstrated abnormal branching of the cephalic vessels in E11.5 mutant embryos. The carotid and vertebral arteries showed an increase in caliber that was related to reduced vascular smooth muscle coverage. Taking advantage of a newly constructed Msx1(CreERT2) allele, we demonstrated by lineage tracing that the primary defect lies in a population of VSMC precursors. The abnormal phenotype that ensues is a consequence of impaired BMP signaling in the VSMC precursors that leads to downregulation of the metalloprotease 2 (Mmp2) and Mmp9 genes, which are essential for cell migration and integration into the mural layer. Improper coverage by VSMCs secondarily leads to incomplete maturation of the endothelial layer. Our results demonstrate that both Msx1 and Msx2 are required for the recruitment of a population of neural crest-derived VSMCs.

  10. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    OpenAIRE

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  11. ESPRIT: A Method for Defining Soluble Expression Constructs in Poorly Understood Gene Sequences.

    Science.gov (United States)

    Mas, Philippe J; Hart, Darren J

    2017-01-01

    Production of soluble, purifiable domains or multi-domain fragments of proteins is a prerequisite for structural biology and other applications. When target sequences are poorly annotated, or when there are few similar sequences available for alignments, identification of domains can be problematic. A method called expression of soluble proteins by random incremental truncation (ESPRIT) addresses this problem by high-throughput automated screening of tens of thousands of enzymatically truncated gene fragments. Rare soluble constructs are identified by experimental screening, and the boundaries revealed by DNA sequencing.

  12. An intersectional gene regulatory strategy defines subclass diversity of C. elegans motor neurons.

    Science.gov (United States)

    Kratsios, Paschalis; Kerk, Sze Yen; Catela, Catarina; Liang, Joseph; Vidal, Berta; Bayer, Emily A; Feng, Weidong; De La Cruz, Estanisla Daniel; Croci, Laura; Consalez, G Giacomo; Mizumoto, Kota; Hobert, Oliver

    2017-07-05

    A core principle of nervous system organization is the diversification of neuron classes into subclasses that share large sets of features but differ in select traits. We describe here a molecular mechanism necessary for motor neurons to acquire subclass-specific traits in the nematode Caenorhabditis elegans . Cholinergic motor neuron classes of the ventral nerve cord can be subdivided into subclasses along the anterior-posterior (A-P) axis based on synaptic connectivity patterns and molecular features. The conserved COE-type terminal selector UNC-3 not only controls the expression of traits shared by all members of a neuron class, but is also required for subclass-specific traits expressed along the A-P axis. UNC-3, which is not regionally restricted, requires region-specific cofactors in the form of Hox proteins to co-activate subclass-specific effector genes in post-mitotic motor neurons. This intersectional gene regulatory principle for neuronal subclass diversification may be conserved from nematodes to mice.

  13. Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.

    Science.gov (United States)

    Savic, Daniel; Ramaker, Ryne C; Roberts, Brian S; Dean, Emma C; Burwell, Todd C; Meadows, Sarah K; Cooper, Sara J; Garabedian, Michael J; Gertz, Jason; Myers, Richard M

    2016-07-11

    The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking. To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns. Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic

  14. High-Throughput Gene Expression Profiles to Define Drug Similarity and Predict Compound Activity.

    Science.gov (United States)

    De Wolf, Hans; Cougnaud, Laure; Van Hoorde, Kirsten; De Bondt, An; Wegner, Joerg K; Ceulemans, Hugo; Göhlmann, Hinrich

    2018-04-01

    By adding biological information, beyond the chemical properties and desired effect of a compound, uncharted compound areas and connections can be explored. In this study, we add transcriptional information for 31K compounds of Janssen's primary screening deck, using the HT L1000 platform and assess (a) the transcriptional connection score for generating compound similarities, (b) machine learning algorithms for generating target activity predictions, and (c) the scaffold hopping potential of the resulting hits. We demonstrate that the transcriptional connection score is best computed from the significant genes only and should be interpreted within its confidence interval for which we provide the stats. These guidelines help to reduce noise, increase reproducibility, and enable the separation of specific and promiscuous compounds. The added value of machine learning is demonstrated for the NR3C1 and HSP90 targets. Support Vector Machine models yielded balanced accuracy values ≥80% when the expression values from DDIT4 & SERPINE1 and TMEM97 & SPR were used to predict the NR3C1 and HSP90 activity, respectively. Combining both models resulted in 22 new and confirmed HSP90-independent NR3C1 inhibitors, providing two scaffolds (i.e., pyrimidine and pyrazolo-pyrimidine), which could potentially be of interest in the treatment of depression (i.e., inhibiting the glucocorticoid receptor (i.e., NR3C1), while leaving its chaperone, HSP90, unaffected). As such, the initial hit rate increased by a factor 300, as less, but more specific chemistry could be screened, based on the upfront computed activity predictions.

  15. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

    Science.gov (United States)

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

    2017-05-01

    A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. 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

  17. Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples

    Directory of Open Access Journals (Sweden)

    Marcella Zollino

    2017-10-01

    Full Text Available Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15–30% of cases craniosynostosis occurs in association with other physical anomalies and it is referred to as syndromic craniosynostosis. Syndromic forms of craniosynostosis arise from mutations in genes belonging to the Fibroblast Growth Factor Receptor (FGFR family and the interconnected molecular pathways in most cases. However it can occur in association with other gene variants and with a variety of chromosome abnormalities as well, usually in association with intellectual disability (ID and additional physical anomalies. Evaluating the molecular properties of the genes undergoing intragenic mutations or copy number variations (CNVs along with prevalence of craniosynostosis in different conditions and animal models if available, we made an attempt to define two distinct groups of unusual syndromic craniosynostosis, which can reflect direct effects of emerging new candidate genes with roles in suture homeostasis or a non-specific phenotypic manifestation of pleiotropic genes, respectively. RASopathies and 9p23p22.3 deletions are reviewed as examples of conditions in the first group. In particular, we found that craniosynostosis is a relatively common component manifestation of cardio-facio-cutaneous (CFC syndrome. Chromatinopathies and neurocristopathies are presented as examples of conditions in the second group. We observed that craniosynostosis is uncommon on average in these conditions. It was randomly associated with Kabuki, Koolen-de Vries/KANSL1 haploinsufficiency and Mowat–Wilson syndromes and in KAT6B-related disorders. As an exception, trigonocephaly in Bohring-Opitz syndrome reflects specific molecular properties of the chromatin modifier ASXL1 gene. Surveillance for craniosynostosis in syndromic forms of

  18. Multicolor fluorescent in situ hybridization to define abutting and overlapping gene expression in the embryonic zebrafish brain

    Directory of Open Access Journals (Sweden)

    Hauptmann Giselbert

    2011-04-01

    Full Text Available Abstract Background In recent years, mapping of overlapping and abutting regulatory gene expression domains by chromogenic two-color in situ hybridization has helped define molecular subdivisions of the developing vertebrate brain and shed light on its basic organization. Despite the benefits of this technique, visualization of overlapping transcript distributions by differently colored precipitates remains difficult because of masking of lighter signals by darker color precipitates and lack of three-dimensional visualization properties. Fluorescent detection of transcript distributions may be able to solve these issues. However, despite the use of signal amplification systems for increasing sensitivity, fluorescent detection in whole-mounts suffers from rapid quenching of peroxidase (POD activity compared to alkaline phosphatase chromogenic reactions. Thus, less strongly expressed genes cannot be efficiently detected. Results We developed an optimized procedure for fluorescent detection of transcript distribution in whole-mount zebrafish embryos using tyramide signal amplification (TSA. Conditions for hybridization and POD-TSA reaction were optimized by the application of the viscosity-increasing polymer dextran sulfate and the use of the substituted phenol compounds 4-iodophenol and vanillin as enhancers of POD activity. In combination with highly effective bench-made tyramide substrates, these improvements resulted in dramatically increased signal-to-noise ratios. The strongly enhanced signal intensities permitted fluorescent visualization of less abundant transcripts of tissue-specific regulatory genes. When performing multicolor fluorescent in situ hybridization (FISH experiments, the highly sensitive POD reaction conditions required effective POD inactivation after each detection cycle by glycine-hydrochloric acid treatment. This optimized FISH procedure permitted the simultaneous fluorescent visualization of up to three unique transcripts

  19. FBN1 gene mutation defines the profibrillin to fibrillin processing site and segregates with tall stature in a family

    Energy Technology Data Exchange (ETDEWEB)

    Grossfield, J.; Cao, S.; Milewicz, D. [Univ. of Texas Medical School, Houston, TX (United States)] [and others

    1994-09-01

    Dermal fibroblasts from a 13-year-old boy with skeletal features of the Marfan syndrome were used to study fibrillin synthesis and processing. Synthesis and secretion of profibrillin was normal but only half of the secreted profibrillin was converted to fibrillin, an extracellular proteolytic processing that removes a 20 kDa fragment from the protein. All the secreted profibrillin was processed to fibrillin in control cells. Only the processed form of fibrillin was deposited into the extracellular matrix in both the proband`s and the control cells. Electron microscopic examination of rotary shadowed microfibrils made by the proband`s fibroblasts were indistinguishable from control cells. Screening exons in the 3{prime} end of the FBN1 gene revealed a heterozygous C to T transition at nucleotide 5482 of the FBN1 cDNA changing R 1828 to W. This mutation disrupts a known consensus sequence recognized by a cellular protease and is located in the carboxy terminus at a site predicted to remove a 19 kD fragment. The proband and his 22-year-old brother, also heterozygous for the mutation, have had normal echocardiograms and ophthalmologic exams. The mutation segregated in the proband`s three generation family with autosomal dominant inheritance of height (> 90th percentile) and no known cardiovascular or ocular problems, including the 67-year-old grandmother (exams pending). The mutation was not found in 90 chromosomes from unrelated individuals. In summary, (1) the mutation identifies the cleavage site for the conversion of profibrillin to fibrillin; (2) the characterized mutation segregates in the family with tall stature without known cardiovascular or ocular problems; (3) this mutation potentially defines the phenotype associated with a {open_quotes}null{close_quotes} allele for the FBN1 gene.

  20. Well-defined block copolymers for gene delivery to dendritic cells: probing the effect of polycation chain-length.

    Science.gov (United States)

    Tang, Rupei; Palumbo, R Noelle; Nagarajan, Lakshmi; Krogstad, Emily; Wang, Chun

    2010-03-03

    The development of safe and efficient polymer carriers for DNA vaccine delivery requires mechanistic understanding of structure-function relationship of the polymer carriers and their interaction with antigen-presenting cells. Here we have synthesized a series of diblock copolymers with well-defined chain-length using atom transfer radical polymerization and characterized the influence of polycation chain-length on the physico-chemical properties of the polymer/DNA complexes as well as the interaction with dendritic cells. The copolymers consist of a hydrophilic poly(ethylene glycol) block and a cationic poly(aminoethyl methacrylate) (PAEM) block. The average degree of polymerization (DP) of the PAEM block was varied among 19, 39, and 75, with nearly uniform distribution. With increasing PAEM chain-length, polyplexes formed by the diblock copolymers and plasmid DNA had smaller average particle size and showed higher stability against electrostatic destabilization by salt and heparin. The polymers were not toxic to mouse dendritic cells (DCs) and only displayed chain-length-dependent toxicity at a high concentration (1mg/mL). In vitro gene transfection efficiency and polyplex uptake in DCs were also found to correlate with chain-length of the PAEM block with the longer polymer chain favoring transfection and cellular uptake. The polyplexes induced a modest up-regulation of surface markers for DC maturation that was not significantly dependent on PAEM chain-length. Finally, the polyplex prepared from the longest PAEM block (DP of 75) achieved an average of 20% enhancement over non-condensed anionic dextran in terms of uptake by DCs in the draining lymph nodes 24h after subcutaneous injection into mice. Insights gained from studying such structurally well-defined polymer carriers and their interaction with dendritic cells may contribute to improved design of practically useful DNA vaccine delivery systems. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Brian W Kunkle

    Full Text Available In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV, and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated. These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  2. Hepatic transcriptome analysis of hepatitis C virus infection in chimpanzees defines unique gene expression patterns associated with viral clearance.

    Directory of Open Access Journals (Sweden)

    Santosh Nanda

    Full Text Available Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon stimulated genes were induced irrespective of the outcome of infection. Early induction of a set of genes associated with cell proliferation and immune activation was associated with subsequent viral clearance. Specifically, two of the genes: interleukin binding factor 3 (ILF3 and cytotoxic granule-associated RNA binding protein (TIA1, associated with robust T-cell response, were highly induced early in chimpanzees with self-limited infection. Up-regulation of genes associated with CD8+ T cell response was evident only during the clearance phase of the acute self-limited infection. The induction of these genes may represent an initial response of cellular injury and proliferation that successfully translates to a "danger signal" leading to induction of adaptive immunity to control viral infection. This primary difference in hepatic gene expression between self-limited and chronic infections supports the concept that successful activation of HCV-specific T-cell response is critical in clearance of acute HCV infection.

  3. Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

    Science.gov (United States)

    Kunkle, Brian W.; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors. PMID:23737970

  4. Nonsynonymous substitution rate (Ka is a relatively consistent parameter for defining fast-evolving and slow-evolving protein-coding genes

    Directory of Open Access Journals (Sweden)

    Wang Lei

    2011-02-01

    /Ks, can be used as a parameter to sort genes by evolution rate and can also provide a way to categorize common protein functions and define their interaction networks, either pair-wise or in defined lineages or subgroups. Evaluating gene evolution based on Ka and Ks calculations can be done with large datasets, such as mammalian genomes. Reviewers This article has been reviewed by Drs. Anamaria Necsulea (nominated by Nicolas Galtier, Subhajyoti De (nominated by Sarah Teichmann and Claus O. Wilke.

  5. Quantitative changes of main components of erythrocyte membranes which define architectonics of cells under pttg gene knockout

    Directory of Open Access Journals (Sweden)

    О. P. Kanyuka

    2014-04-01

    Full Text Available A pttg gene knockout affects the functional state of erythron in mice which could be associated with structural changes in the structure of erythrocyte membranes. The pttg gene knockout causes a significant modification of fatty acids composition of erythrocyte membrane lipids by reducing the content of palmitic acid and increasing of polyunsaturated fatty acids amount by 18%. Analyzing the erythrocyte surface architectonics of mice under pttg gene knockout, it was found that on the background of reduction of the functionally complete biconcave discs population one could observe an increase of the number of transformed cells at different degeneration stages. Researches have shown that in mice with a pttg gene knockout compared with a control group of animals cytoskeletal protein – β-spectrin was reduced by 17.03%. However, there is a reduction of membrane protein band 3 by 33.04%, simultaneously the content of anion transport protein band 4.5 increases by 35.2% and protein band 4.2 by 32.1%. The lectin blot analysis has helped to reveal changes in the structure of the carbohydrate determinants of ery­throcyte membrane glycoproteins under conditions of directed pttg gene inactivation, accompanied by changes in the type of communication, which joins the terminal residue in carbohydrate determinant of glycoproteins. Thus, a significant redistribution of protein and fatty acids contents in erythrocyte membranes that manifested in the increase of the deformed shape of red blood cells is observed under pttg gene knockout.

  6. Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress.

    Directory of Open Access Journals (Sweden)

    Tiziana Triulzi

    Full Text Available We recently showed that differential expression of extracellular matrix (ECM genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4 with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p = 0.001. Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR = 3.0, 95% CI = 1.3-7.0, p = 0.0098. Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III phenotype. These findings support the

  7. Single-copy genes define a conserved order between rice and wheat for understanding differences caused by duplication, deletion, and transposition of genes.

    Science.gov (United States)

    Singh, Nagendra K; Dalal, Vivek; Batra, Kamlesh; Singh, Binay K; Chitra, G; Singh, Archana; Ghazi, Irfan A; Yadav, Mahavir; Pandit, Awadhesh; Dixit, Rekha; Singh, Pradeep K; Singh, Harvinder; Koundal, Kirpa R; Gaikwad, Kishor; Mohapatra, Trilochan; Sharma, Tilak R

    2007-01-01

    The high-quality rice genome sequence is serving as a reference for comparative genome analysis in crop plants, especially cereals. However, early comparisons with bread wheat showed complex patterns of conserved synteny (gene content) and colinearity (gene order). Here, we show the presence of ancient duplicated segments in the progenitor of wheat, which were first identified in the rice genome. We also show that single-copy (SC) rice genes, those representing unique matches with wheat expressed sequence tag (EST) unigene contigs in the whole rice genome, show more than twice the proportion of genes mapping to syntenic wheat chromosome as compared to the multicopy (MC) or duplicated rice genes. While 58.7% of the 1,244 mapped SC rice genes were located in single syntenic wheat chromosome groups, the remaining 41.3% were distributed randomly to the other six non-syntenic wheat groups. This could only be explained by a background dispersal of genes in the genome through transposition or other unknown mechanism. The breakdown of rice-wheat synteny due to such transpositions was much greater near the wheat centromeres. Furthermore, the SC rice genes revealed a conserved primordial gene order that gives clues to the origin of rice and wheat chromosomes from a common ancestor through polyploidy, aneuploidy, centromeric fusions, and translocations. Apart from the bin-mapped wheat EST contigs, we also compared 56,298 predicted rice genes with 39,813 wheat EST contigs assembled from 409,765 EST sequences and identified 7,241 SC rice gene homologs of wheat. Based on the conserved colinearity of 1,063 mapped SC rice genes across the bins of individual wheat chromosomes, we predicted the wheat bin location of 6,178 unmapped SC rice gene homologs and validated the location of 213 of these in the telomeric bins of 21 wheat chromosomes with 35.4% initial success. This opens up the possibility of directed mapping of a large number of conserved SC rice gene homologs in wheat

  8. Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

    Science.gov (United States)

    Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

    2015-01-01

    Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID

  9. Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

    Directory of Open Access Journals (Sweden)

    Manoj Bhasin

    Full Text Available Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC and medial smooth muscle cells (SMC from canine vein grafts, 2 hours (H to 30 days (D following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1 signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1, a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.

  10. Growth and sporulation of Bacillus cereus ATCC 14579 under defined conditions: temporal expression of genes for key sigma factors

    NARCIS (Netherlands)

    Vries, de Y.P.; Hornstra, L.M.; Vos, de W.M.; Abee, T.

    2004-01-01

    An airlift fermentor system allowing precise regulation of pH and aeration combined with a chemically defined medium was used to study growth and sporulation of Bacillus cereus ATCC 14579. Sporulation was complete and synchronous. Expression of sigA, sigB, sigF, and sigG was monitored with real-time

  11. Defining global gene expression changes of the hypothalamic-pituitary-gonadal axis in female sGnRH-antisense transgenic common carp (Cyprinus carpio.

    Directory of Open Access Journals (Sweden)

    Jing Xu

    Full Text Available BACKGROUND: The hypothalamic-pituitary-gonadal (HPG axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus, 16 and 12 (pituitary, 119 and 93 (ovary, respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the

  12. Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

    Science.gov (United States)

    Xu, Jing; Huang, Wei; Zhong, Chengrong; Luo, Daji; Li, Shuangfei; Zhu, Zuoyan; Hu, Wei

    2011-01-01

    Background The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. Methodology/Principal Findings In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. Conclusions/Significance This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of

  13. Structural defect linked to nonrandom mutations in the matrix gene of Biden strain subacute sclerosing panencephalitis virus defined by cDNA cloning and expression of chimeric genes

    International Nuclear Information System (INIS)

    Ayata, M.; Hirano, A.; Wong, T.C.

    1989-01-01

    Biken strain, a nonproductive measles viruslike agent isolated from a subacute sclerosing panencephalitis (SSPE) patient, contains a posttranscriptional defect affecting matrix (M) protein. A putative M protein was translated in vitro with RNA from Biken strain-infected cells. A similar protein was detected in vivo by an antiserum against a peptide synthesized from the cloned M gene of Edmonston strain measles virus. By using a novel method, full-length cDNAs of the Biken M gene were selectively cloned. The cloned Biken M gene contained an open reading frame which encoded 8 extra carboxy-terminal amino acid residues and 20 amino acid substitutions predicted to affect both the hydrophobicity and secondary structure of the gene product. The cloned gene was expressed in vitro and in vivo into a 37,500 M r protein electrophoretically and antigenically distinct from the M protein of Edmonston strain but identical to the M protein in Biken strain-infected cells. Chimeric M proteins synthesized in vitro and in vivo showed that the mutations in the carboxy-proximal region altered the local antigenicity and those in the amino region affected the overall protein conformation. The protein expressed from the Biken M gene was unstable in vivo. Instability was attributed to multiple mutations. These results offer insights into the basis of the defect in Biken strain and pose intriguing questions about the evolutionary origins of SSPE viruses in general

  14. Public data mining plus domestic experimental study defined involvement of the old-yet-uncharacterized gene matrix-remodeling associated 7 (MXRA7) in physiopathology of the eye.

    Science.gov (United States)

    Jia, Changkai; Zhang, Feng; Zhu, Ying; Qi, Xia; Wang, Yiqiang

    2017-10-20

    Matrix-remodeling associated 7 (MXRA7) gene was first reported in 2002 and named so for its co-expression with several genes known to relate with matrix-remodeling. However, not any studies had been intentionally performed to characterize this gene. We started defining the functions of MXRA7 by integrating bioinformatics analysis and experimental study. Data mining of MXRA7 expression in BioGPS, Gene Expression Omnibus and EurExpress platforms highlighted high level expression of Mxra7 in murine ocular tissues. Real-time PCR was employed to measure Mxra7 mRNA in tissues of adult C57BL/6 mice and demonstrated that Mxra7 was preferentially expressed at higher level in retina, corneas and lens than in other tissues. Then the inflammatory corneal neovascularization (CorNV) model and fungal corneal infections were induced in Balb/c mice, and mRNA levels of Mxra7 as well as several matrix-remodeling related genes (Mmp3, Mmp13, Ecm1, Timp1) were monitored with RT-PCR. The results demonstrated a time-dependent Mxra7 under-expression pattern (U-shape curve along timeline), while all other matrix-remodeling related genes manifested an opposite changes pattern (dome-shape curve). When limited data from BioGPS concerning human MXRA7 gene expression in human tissues were looked at, it was found that ocular tissue was also the one expressing highest level of MXRA7. To conclude, integrative assay of MXRA7 gene expression in public databank as well as domestic animal models revealed a selective high expression MXRA7 in murine and human ocular tissues, and its change patterns in two corneal disease models implied that MXRA7 might play a role in pathological processes or diseases involving injury, neovascularization and would healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

    Science.gov (United States)

    Bienertova-Vasku, Julie; Bienert, Petr; Tomandl, Josef; Forejt, Martin; Vavrina, Martin; Kudelkova, Jana; Vasku, Anna

    2008-02-01

    Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

  16. uvsI mutants defective in UV mutagenesis define a fourth epistatic group of uvs genes in Aspergillus.

    Science.gov (United States)

    Chae, S K; Kafer, E

    1993-01-01

    Three UV-sensitive mutations of A. nidulans, uvsI, uvsJ and uvsA, were tested for epistatic relationships with members of the previously established groups, here called the "UvsF", "UvsC", and "UvsB" groups. uvsI mutants are defective for spontaneous and induced reversion of certain point mutations and differ also for other properties from previously analyzed uvs types. They are very sensitive to the killing effects of UV-light and 4-NQO (4-nitro-quinoline-N-oxide) but not to MMS (methylmethane sulfonate). When double- and single-mutant uvs strains were compared for sensitivity to these three agents, synergistic or additive effects were found for uvsI with all members of the three groups. The uvsI gene may therefore represent a fourth epistatic group, possibly involved in mutagenic repair. On the other hand, uvsJ was clearly epistatic with members of the UvsF group and fitted well into this group also by phenotype. The uvsA gene was tentatively assigned to the UvsC group. uvsA showed epistatic interactions with uvsC in all tests, and like UvsC-group mutants is UV-sensitive mainly in dividing cells. However, the uvsA mutation does not cause the defects in recombination and UV mutagenesis typical for this group.

  17. Fixed differences in the paralytic gene define two lineages within the Lutzomyia longipalpis complex producing different types of courtship songs.

    Directory of Open Access Journals (Sweden)

    Rachel M M A Lins

    Full Text Available The sand fly Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae, the most important vector of American visceral leishmaniasis, is widely distributed in Latin America. There is currently a consensus that it represents a species complex, however, the number and distribution of the different siblings is still uncertain. Previous analyses have indicated that Brazilian populations of this vector can be divided into two main groups according to the type of courtship song (Burst vs. Pulse males produce during copulation. Nevertheless, no diagnostic differences have been observed between these two groups with most molecular markers used to date. We analyzed the molecular divergence in a fragment of the paralytic (para gene, a locus involved in the control of courtship songs in Drosophila, among a number of Lu. longipalpis populations from Brazil producing Burst and Pulse-type songs. Our results revealed a very high level of divergence and fixed differences between populations producing the two types of songs. We also compared Lu. longipalpis with a very closely related species, Lutzomyia cruzi, which produces Burst-type songs. The results indicated a higher number of fixed differences between Lu. cruzi and the Pulse-type populations of Lu. longipalpis than with those producing Burst-type songs. The data confirmed our previous assumptions that the presence of different sibling species of the Lu. longipalpis complex in Brazil can be divided into two main groups, one representing a single species and a second more heterogeneous group that probably represents a number of incipient species. We hypothesize that para might be one of the genes directly involved in the control of the courtship song differences between these two groups or that it is linked to other loci associated with reproductive isolation of the Brazilian species.

  18. Fixed Differences in the paralytic Gene Define Two Lineages within the Lutzomyia longipalpis Complex Producing Different Types of Courtship Songs

    Science.gov (United States)

    Lins, Rachel M. M. A.; Souza, Nataly A.; Brazil, Reginaldo P.; Maingon, Rhayza D. C.; Peixoto, Alexandre A.

    2012-01-01

    The sand fly Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae), the most important vector of American visceral leishmaniasis, is widely distributed in Latin America. There is currently a consensus that it represents a species complex, however, the number and distribution of the different siblings is still uncertain. Previous analyses have indicated that Brazilian populations of this vector can be divided into two main groups according to the type of courtship song (Burst vs. Pulse) males produce during copulation. Nevertheless, no diagnostic differences have been observed between these two groups with most molecular markers used to date. We analyzed the molecular divergence in a fragment of the paralytic (para) gene, a locus involved in the control of courtship songs in Drosophila, among a number of Lu. longipalpis populations from Brazil producing Burst and Pulse-type songs. Our results revealed a very high level of divergence and fixed differences between populations producing the two types of songs. We also compared Lu. longipalpis with a very closely related species, Lutzomyia cruzi, which produces Burst-type songs. The results indicated a higher number of fixed differences between Lu. cruzi and the Pulse-type populations of Lu. longipalpis than with those producing Burst-type songs. The data confirmed our previous assumptions that the presence of different sibling species of the Lu. longipalpis complex in Brazil can be divided into two main groups, one representing a single species and a second more heterogeneous group that probably represents a number of incipient species. We hypothesize that para might be one of the genes directly involved in the control of the courtship song differences between these two groups or that it is linked to other loci associated with reproductive isolation of the Brazilian species. PMID:22970200

  19. Genetic localisation of MRX27 to Xq24-26 defines another discrete gene for non-specific X-linked mental retardation

    Energy Technology Data Exchange (ETDEWEB)

    Gedeon, A.K.; Connor, J.M.; Mulley, J.C. [Univ. of Adelaide (Australia); Connor, J.M. [Duncan Guthrie Inst. of Medical Genetics, Yorkhill (United Kingdom); Glass, I.A. [Univ. of California, San Franciso, CA (United States)

    1996-07-12

    A large family with non-specific X-linked mental retardation (MRX) was first described in 1991, with a suggestion of linkage to Xq26-27. The maximum lod score was 1.60 ({theta} = 0.10) with the F9 locus. The localization of this MRX gene has now been established by linkage to microsatellite markers. Peak pairwise lod scores of 4.02 and 4.01 ({theta} = 0.00) were attained at the DXS1114 and DXS994 loci respectively. This MRX gene is now designated MRX27 and is localized to Xq24-26 by recombination events detected by DXS424 and DXS102. This regional localization spans 26.2 cM on the genetic background map and defines another distinct MRX interval by linkage to a specific region of the X chromosome. 25 refs., 1 fig., 1 tab.

  20. Race/Ethnic Based Genetic Variations in Human Genes: Defining the Genetic Evidence for Disparity of Prostate Cancer Risk and Mortality Between Different Populations

    National Research Council Canada - National Science Library

    Franklin, John

    1999-01-01

    .... The study will evaluate variations in androgen receptor gene, the vitamin D receptor gene, and the APOJ/clusterin gene by amplifying specific DNA segments from certain genes utilizing a commonly used...

  1. 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....

  2. "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.

  3. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Bodei, L.; Kidd, M.; Modlin, I.M.; Severi, S.; Nicolini, S.; Paganelli, G.; Drozdov, I.; Kwekkeboom, D.J.; Krenning, E.P.; Baum, R.P.

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with 177 Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 18 FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ 2 = 27.4; p = 1.2 x 10 -7 ) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting

  4. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Kidd, M. [Wren Laboratories, Branford, CT (United States); Modlin, I.M. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Yale School of Medicine, New Haven, CT (United States); Severi, S.; Nicolini, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Drozdov, I. [Bering Limited, London (United Kingdom); Kwekkeboom, D.J.; Krenning, E.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Erasmus Medical Center, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2016-05-15

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with {sup 177}Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 {sup 18}FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ{sup 2} = 27.4; p = 1.2 x 10{sup -7}) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0

  5. 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.

  6. 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.

  7. HFE gene polymorphism defined by sequence-based typing of the Brazilian population and a standardized nomenclature for HFE allele sequences.

    Science.gov (United States)

    Campos, W N; Massaro, J D; Martinelli, A L C; Halliwell, J A; Marsh, S G E; Mendes-Junior, C T; Donadi, E A

    2017-10-01

    The HFE molecule controls iron uptake from gut, and defects in the molecule have been associated with iron overload, particularly in hereditary hemochromatosis. The HFE gene including both coding and boundary intronic regions were sequenced in 304 Brazilian individuals, encompassing healthy individuals and patients exhibiting hereditary or acquired iron overload. Six sites of variation were detected: (1) H63D C>G in exon 2, (2) IVS2 (+4) T>C in intron 2, (3) a C>G transversion in intron 3, (4) C282Y G>A in exon 4, (5) IVS4 (-44) T>C in intron 4, and (6) a new guanine deletion (G>del) in intron 5, which were used for haplotype inference. Nine HFE alleles were detected and six of these were officially named on the basis of the HLA Nomenclature, defined by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System, and published via the IPD-IMGT/HLA website. Four alleles, HFE*001, *002, *003, and *004 exhibited variation within their exon sequences. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Defining suitable reference genes for RT-qPCR analysis on human sertoli cells after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

    Science.gov (United States)

    Ribeiro, Mariana Antunes; dos Reis, Mariana Bisarro; de Moraes, Leonardo Nazário; Briton-Jones, Christine; Rainho, Cláudia Aparecida; Scarano, Wellerson Rodrigo

    2014-11-01

    Quantitative real-time RT-PCR (qPCR) has proven to be a valuable molecular technique to quantify gene expression. There are few studies in the literature that describe suitable reference genes to normalize gene expression data. Studies of transcriptionally disruptive toxins, like tetrachlorodibenzo-p-dioxin (TCDD), require careful consideration of reference genes. The present study was designed to validate potential reference genes in human Sertoli cells after exposure to TCDD. 32 candidate reference genes were analyzed to determine their applicability. geNorm and NormFinder softwares were used to obtain an estimation of the expression stability of the 32 genes and to identify the most suitable genes for qPCR data normalization.

  9. Loss of lager specific genes and subtelomeric regions define two different Saccharomyces cerevisiae lineages for Saccharomyces pastorianus Group I and II strains.

    Science.gov (United States)

    Monerawela, Chandre; James, Tharappel C; Wolfe, Kenneth H; Bond, Ursula

    2015-03-01

    Lager yeasts, Saccharomyces pastorianus, are interspecies hybrids between S. cerevisiae and S. eubayanus and are classified into Group I and Group II clades. The genome of the Group II strain, Weihenstephan 34/70, contains eight so-called 'lager-specific' genes that are located in subtelomeric regions. We evaluated the origins of these genes through bioinformatic and PCR analyses of Saccharomyces genomes. We determined that four are of cerevisiae origin while four originate from S. eubayanus. The Group I yeasts contain all four S. eubayanus genes but individual strains contain only a subset of the cerevisiae genes. We identified S. cerevisiae strains that contain all four cerevisiae 'lager-specific' genes, and distinct patterns of loss of these genes in other strains. Analysis of the subtelomeric regions uncovered patterns of loss in different S. cerevisiae strains. We identify two classes of S. cerevisiae strains: ale yeasts (Foster O) and stout yeasts with patterns of 'lager-specific' genes and subtelomeric regions identical to Group I and II S. pastorianus yeasts, respectively. These findings lead us to propose that Group I and II S. pastorianus strains originate from separate hybridization events involving different S. cerevisiae lineages. Using the combined bioinformatic and PCR data, we describe a potential classification map for industrial yeasts. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  10. 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

  11. In vitro modeling of human pancreatic duct epithelial cell transformation defines gene expression changes induced by K-ras oncogenic activation in pancreatic carcinogenesis.

    Science.gov (United States)

    Qian, Jiaying; Niu, Jiangong; Li, Ming; Chiao, Paul J; Tsao, Ming-Sound

    2005-06-15

    Genetic analysis of pancreatic ductal adenocarcinomas and their putative precursor lesions, pancreatic intraepithelial neoplasias (PanIN), has shown a multistep molecular paradigm for duct cell carcinogenesis. Mutational activation or inactivation of the K-ras, p16(INK4A), Smad4, and p53 genes occur at progressive and high frequencies in these lesions. Oncogenic activation of the K-ras gene occurs in >90% of pancreatic ductal carcinoma and is found early in the PanIN-carcinoma sequence, but its functional roles remain poorly understood. We show here that the expression of K-ras(G12V) oncogene in a near diploid HPV16-E6E7 gene immortalized human pancreatic duct epithelial cell line originally derived from normal pancreas induced the formation of carcinoma in 50% of severe combined immunodeficient mice implanted with these cells. A tumor cell line established from one of these tumors formed ductal cancer when implanted orthotopically. These cells also showed increased activation of the mitogen-activated protein kinase, AKT, and nuclear factor-kappaB pathways. Microarray expression profiling studies identified 584 genes whose expression seemed specifically up-regulated by the K-ras oncogene expression. Forty-two of these genes have been reported previously as differentially overexpressed in pancreatic cancer cell lines or primary tumors. Real-time PCR confirmed the overexpression of a large number of these genes. Immunohistochemistry done on tissue microarrays constructed from PanIN and pancreatic cancer samples showed laminin beta3 overexpression starting in high-grade PanINs and occurring in >90% of pancreatic ductal carcinoma. The in vitro modeling of human pancreatic duct epithelial cell transformation may provide mechanistic insights on gene expression changes that occur during multistage pancreatic duct cell carcinogenesis.

  12. A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

    Science.gov (United States)

    Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

    2014-01-01

    Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

  13. A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

    Directory of Open Access Journals (Sweden)

    Teruhiko Suzuki

    Full Text Available Human artificial chromosomes (HACs are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

  14. Comparative genomics defines the core genome of the growing N4-like phage genus and identifies N4-like Roseophage specific genes

    Directory of Open Access Journals (Sweden)

    Jacqueline Zoe-Munn Chan

    2014-10-01

    Full Text Available Two bacteriophages, RPP1 and RLP1, infecting members of the marine Roseobacter clade were isolated from seawater. Their linear genomes are 74.7 and 74.6 kb and encode 91 and 92 coding DNA sequences, respectively. Around 30% of these are homologous to genes found in Enterobacter phage N4. Comparative genomics of these two new Roseobacter phages and twenty-three other sequenced N4-like phages (three infecting members of the Roseobacter lineage and twenty infecting other Gammaproteobacteria revealed that N4-like phages share a core genome of 14 genes responsible for control of gene expression, replication and virion proteins. Phylogenetic analysis of these genes placed the five N4-like roseophages (RN4 into a distinct subclade. Analysis of the RN4 phage genomes revealed they share a further 19 genes of which nine are found exclusively in RN4 phages and four appear to have been acquired from their bacterial hosts. Proteomic analysis of the RPP1 and RLP1 virions identified a second structural module present in the RN4 phages similar to that found in the Pseudomonas N4-like phage LIT1. Searches of various metagenomic databases, included the GOS database, using CDS sequences from RPP1 suggests these phages are widely distributed in marine environments in particular in the open ocean environment.

  15. Array-based gene expression, CGH and tissue data defines a 12q24 gain in neuroblastic tumors with prognostic implication

    Directory of Open Access Journals (Sweden)

    Kilpinen Sami

    2010-05-01

    Full Text Available Abstract Background Neuroblastoma has successfully served as a model system for the identification of neuroectoderm-derived oncogenes. However, in spite of various efforts, only a few clinically useful prognostic markers have been found. Here, we present a framework, which integrates DNA, RNA and tissue data to identify and prioritize genetic events that represent clinically relevant new therapeutic targets and prognostic biomarkers for neuroblastoma. Methods A single-gene resolution aCGH profiling was integrated with microarray-based gene expression profiling data to distinguish genetic copy number alterations that were strongly associated with transcriptional changes in two neuroblastoma cell lines. FISH analysis using a hotspot tumor tissue microarray of 37 paraffin-embedded neuroblastoma samples and in silico data mining for gene expression information obtained from previously published studies including up to 445 healthy nervous system samples and 123 neuroblastoma samples were used to evaluate the clinical significance and transcriptional consequences of the detected alterations and to identify subsequently activated gene(s. Results In addition to the anticipated high-level amplification and subsequent overexpression of MYCN, MEIS1, CDK4 and MDM2 oncogenes, the aCGH analysis revealed numerous other genetic alterations, including microamplifications at 2p and 12q24.11. Most interestingly, we identified and investigated the clinical relevance of a previously poorly characterized amplicon at 12q24.31. FISH analysis showed low-level gain of 12q24.31 in 14 of 33 (42% neuroblastomas. Patients with the low-level gain had an intermediate prognosis in comparison to patients with MYCN amplification (poor prognosis and to those with no MYCN amplification or 12q24.31 gain (good prognosis (P = 0.001. Using the in silico data mining approach, we identified elevated expression of five genes located at the 12q24.31 amplicon in neuroblastoma (DIABLO, ZCCHC

  16. Turning off flagellum rotation requires the pleiotropic gene pleD: pleA, pleC, and pleD define two morphogenic pathways in Caulobacter crescentus.

    OpenAIRE

    Sommer, J M; Newton, A

    1989-01-01

    We have identified mutations in three pleiotropic genes, pleA, pleC, and pleD, that are required for differentiation in Caulobacter crescentus. pleA and pleC mutants were isolated in an extensive screen for strains defective in both motility and adsorption of polar bacteriophage phi CbK; using temperature-sensitive alleles, we determined the time at which the two genes act. pleA was required for a short period at 0.7 of the swarmer cell cycle for flagellum biosynthesis, whereas pleC was requi...

  17. Single cell analysis of gene expression patterns of competence development and initiation of sporulation in Bacillus subtilis grown on chemically defined media

    NARCIS (Netherlands)

    Veening, J. -W.; Smits, W. K.; Hamoen, L. W.; Kuipers, O. P.

    Aim: Understanding the basis for the heterogeneous (or bistable) expression patterns of competence development and sporulation in Bacillus subtilis. Methods and Results: Using flow cytometric analyses of various promoter-GFP fusions, we have determined the single-cell gene expression patterns of

  18. Development of a cell-defined siRNA microarray for analysis of gene function in human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Hi Chul Kim

    2016-03-01

    The efficiency of this CDSM was verified using three siRNAs (targeting p65, Slug, and N-cadherin, with persistent gene silencing for 5 days. We obtained the significant and reliable data with effective knock-down in our condition, and suggested our method as the qualitatively improved siRNA microarray screening method for hBMSCs.

  19. The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; Daenen, S.; de Jong, B.; Fonatsch, C.; Heinze, B.; Bartram, C.; Hagemeijer, A.; Grosveld, G.

    1992-01-01

    Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and

  20. Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Christine Breynaert

    Full Text Available INTRODUCTION: Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS ingestion, to mimic the relapsing nature of the human disease. MATERIALS AND METHODS: C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total. Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. RESULTS: Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn's colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. CONCLUSIONS: Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn's disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of

  1. Gene transcript analysis blood values correlate with {sup 68}Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Kidd, M.; Modlin, I.M.; Drozdov, I. [Wren Laboratories, Branford, CT (United States); Prasad, V. [Charite University Hospital, Department of Nuclear Medicine, Berlin (Germany); Severi, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Ambrosini, V. [S. Orsola-Malpighi University Hospital, Nuclear Medicine, Bologna (Italy); Kwekkeboom, D.J.; Krenning, E.P. [Erasmus Medical Center Rotterdam, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [Zentralklinik Bad Berka, THERANOSTICS Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2015-08-15

    Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between {sup 68}Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. We utilized two independent patient groups with positive {sup 68}Ga-SSA PET: data set 1 ({sup 68}Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ({sup 68}Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUV{sub max}), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. SUV{sub max} measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ{sup 2} = 20.1, p < 2.5 x 10{sup -6}). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUV{sub max} (R {sup 2} = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUV{sub max}. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUV{sub max} [ROC-derived AUC (R {sup 2} = 0.7, p < 0.05)]. No statistical relationship was identified

  2. Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status

    International Nuclear Information System (INIS)

    Bodei, L.; Kidd, M.; Modlin, I.M.; Drozdov, I.; Prasad, V.; Severi, S.; Paganelli, G.; Ambrosini, V.; Kwekkeboom, D.J.; Krenning, E.P.; Baum, R.P.

    2015-01-01

    Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between 68 Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. We utilized two independent patient groups with positive 68 Ga-SSA PET: data set 1 ( 68 Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ( 68 Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUV max ), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. SUV max measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ 2 = 20.1, p < 2.5 x 10 -6 ). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUV max (R 2 = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUV max . Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUV max [ROC-derived AUC (R 2 = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters

  3. Use of whole genome deep sequencing to define emerging minority variants in virus envelope genes in herpesvirus treated with novel antimicrobial K21.

    Science.gov (United States)

    Tweedy, Joshua G; Prusty, Bhupesh K; Gompels, Ursula A

    2017-10-01

    New antivirals are required to prevent rising antimicrobial resistance from replication inhibitors. The aim of this study was to analyse the range of emerging mutations in herpesvirus by whole genome deep sequencing. We tested human herpesvirus 6 treatment with novel antiviral K21, where evidence indicated distinct effects on virus envelope proteins. We treated BACmid cloned virus in order to analyse mechanisms and candidate targets for resistance. Illumina based next generation sequencing technology enabled analyses of mutations in 85 genes to depths of 10,000 per base detecting low prevalent minority variants (<1%). After four passages in tissue culture the untreated virus accumulated mutations in infected cells giving an emerging mixed population (45-73%) of non-synonymous SNPs in six genes including two envelope glycoproteins. Strikingly, treatment with K21 did not accumulate the passage mutations; instead a high frequency mutation was selected in envelope protein gQ2, part of the gH/gL complex essential for herpesvirus infection. This introduced a stop codon encoding a truncation mutation previously observed in increased virion production. There was reduced detection of the glycoprotein complex in infected cells. This supports a novel pathway for K21 targeting virion envelopes distinct from replication inhibition. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype.

    Science.gov (United States)

    Candido, Juliana B; Morton, Jennifer P; Bailey, Peter; Campbell, Andrew D; Karim, Saadia A; Jamieson, Thomas; Lapienyte, Laura; Gopinathan, Aarthi; Clark, William; McGhee, Ewan J; Wang, Jun; Escorcio-Correia, Monica; Zollinger, Raphael; Roshani, Rozita; Drew, Lisa; Rishi, Loveena; Arkell, Rebecca; Evans, T R Jeffry; Nixon, Colin; Jodrell, Duncan I; Wilkinson, Robert W; Biankin, Andrew V; Barry, Simon T; Balkwill, Frances R; Sansom, Owen J

    2018-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model. Malignant cell proliferation diminished, with increased cell death and an enhanced T cell immune response. Loss of macrophages rewired other features of the TME, with global changes in gene expression akin to switching PDAC subtypes. These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Novel gene fusion of PRCC-MITF defines a new member of MiT family translocation renal cell carcinoma: clinicopathological analysis and detection of the gene fusion by RNA sequencing and FISH.

    Science.gov (United States)

    Xia, Qiu-Yuan; Wang, Xiao-Tong; Ye, Sheng-Bing; Wang, Xuan; Li, Rui; Shi, Shan-Shan; Fang, Ru; Zhang, Ru-Song; Ma, Heng-Hui; Lu, Zhen-Feng; Shen, Qin; Bao, Wei; Zhou, Xiao-Jun; Rao, Qiu

    2018-04-01

    MITF, TFE3, TFEB and TFEC belong to the same microphthalmia-associated transcription factor family (MiT). Two transcription factors in this family have been identified in two unusual types of renal cell carcinoma (RCC): Xp11 translocation RCC harbouring TFE3 gene fusions and t(6;11) RCC harbouring a MALAT1-TFEB gene fusion. The 2016 World Health Organisation classification of renal neoplasia grouped these two neoplasms together under the category of MiT family translocation RCC. RCCs associated with the other two MiT family members, MITF and TFEC, have rarely been reported. Herein, we identify a case of MITF translocation RCC with the novel PRCC-MITF gene fusion by RNA sequencing. Histological examination of the present tumour showed typical features of MiT family translocation RCCs, overlapping with Xp11 translocation RCC and t(6;11) RCC. However, this tumour showed negative results in TFE3 and TFEB immunochemistry and split fluorescence in-situ hybridisation (FISH) assays. The other MiT family members, MITF and TFEC, were tested further immunochemically and also showed negative results. RNA sequencing and reverse transcription-polymerase chain reaction confirmed the presence of a PRCC-MITF gene fusion: a fusion of PRCC exon 5 to MITF exon 4. We then developed FISH assays covering MITF break-apart probes and PRCC-MITF fusion probes to detect the MITF gene rearrangement. This study both proves the recurring existence of MITF translocation RCC and expands the genotype spectrum of MiT family translocation RCCs. © 2017 John Wiley & Sons Ltd.

  6. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  7. 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...

  8. 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....

  9. 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 ...

  10. 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 ...

  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. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. 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

  20. 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....

  1. 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....

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. 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.

  10. 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.

  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. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  13. The neurovirulence and neuroinvasiveness of chimeric tick-borne encephalitis/dengue virus can be attenuated by introducing defined mutations into the envelope and NS5 protein genes and the 3' non-coding region of the genome

    International Nuclear Information System (INIS)

    Engel, Amber R.; Rumyantsev, Alexander A.; Maximova, Olga A.; Speicher, James M.; Heiss, Brian; Murphy, Brian R.; Pletnev, Alexander G.

    2010-01-01

    Tick-borne encephalitis (TBE) is a severe disease affecting thousands of people throughout Eurasia. Despite the use of formalin-inactivated vaccines in endemic areas, an increasing incidence of TBE emphasizes the need for an alternative vaccine that will induce a more durable immunity against TBE virus (TBEV). The chimeric attenuated virus vaccine candidate containing the structural protein genes of TBEV on a dengue virus genetic background (TBEV/DEN4) retains a high level of neurovirulence in both mice and monkeys. Therefore, attenuating mutations were introduced into the envelope (E 315 ) and NS5 (NS5 654,655 ) proteins, and into the 3' non-coding region (Δ30) of TBEV/DEN4. The variant that contained all three mutations (vΔ30/E 315 /NS5 654,655 ) was significantly attenuated for neuroinvasiveness and neurovirulence and displayed a reduced level of replication and virus-induced histopathology in the brains of mice. The high level of safety in the central nervous system indicates that vΔ30/E 315 /NS5 654,655 should be further evaluated as a TBEV vaccine.

  14. 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.

  15. 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.

  16. 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....

  17. Eucaryotic operon genes can define highly conserved syntenies

    Czech Academy of Sciences Publication Activity Database

    Trachtulec, Zdeněk

    2004-01-01

    Roč. 50, - (2004), s. 1-6 ISSN 0015-5500 R&D Projects: GA ČR GA204/01/0997; GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : eukaryotic operon * conserved synteny Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.507, year: 2004

  18. 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.

  19. 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.

  20. 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.

  1. 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....

  2. 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.

  3. 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…

  4. 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.

  5. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  6. 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.

  7. 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.

  8. 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.

  9. Defining the bacteroides ribosomal binding site.

    Science.gov (United States)

    Wegmann, Udo; Horn, Nikki; Carding, Simon R

    2013-03-01

    The human gastrointestinal tract, in particular the colon, hosts a vast number of commensal microorganisms. Representatives of the genus Bacteroides are among the most abundant bacterial species in the human colon. Bacteroidetes diverged from the common line of eubacterial descent before other eubacterial groups. As a result, they employ unique transcription initiation signals and, because of this uniqueness, they require specific genetic tools. Although some tools exist, they are not optimal for studying the roles and functions of these bacteria in the human gastrointestinal tract. Focusing on translation initiation signals in Bacteroides, we created a series of expression vectors allowing for different levels of protein expression in this genus, and we describe the use of pepI from Lactobacillus delbrueckii subsp. lactis as a novel reporter gene for Bacteroides. Furthermore, we report the identification of the 3' end of the 16S rRNA of Bacteroides ovatus and analyze in detail its ribosomal binding site, thus defining a core region necessary for efficient translation, which we have incorporated into the design of our expression vectors. Based on the sequence logo information from the 5' untranslated region of other Bacteroidales ribosomal protein genes, we conclude that our findings are relevant to all members of this order.

  10. 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...

  11. 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...

  12. (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....

  13. 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...

  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. 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.

  17. 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.

  18. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Gene & Cell Therapy Defined Gene therapy and cell therapy are overlapping fields of biomedical research that aim to repair the direct cause of genetic diseases. Read More Gene & Cell Therapy FAQ's Read the most common questions raised by ...

  19. 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.

  20. Polysomy and amplification of chromosome 7 defined for EGFR gene in squamous cell carcinoma of the lung together with exons 19 and 21 wild type Carcinoma epidermóide do pulmão: Polissomia e amplificação do cromossoma 7 e do gene EGRF com forma wild type nos exões 19 e 21

    Directory of Open Access Journals (Sweden)

    Patrícia Couceiro

    2010-06-01

    Full Text Available Purpose: The epidermal growth factor receptor (EGFR is overexpressed in the majority of nonsmall-cell lung cancers (NSCLC and is a major target specific EGFR tyrosine kinase inhibitors (TKIs developed and used for the treatment of advanced NSCLC. A number of biological factors are also associated with EGFR-TKIs responsiveness. This study was focused on EGFR somatic mutations and amplifications in squamous cell lung cancer. Material and methods: Representative sections of squamous cell carcinoma were selected from 54 surgical specimens from formalin-fixed paraffin-embedded tissues and submitted to TMA construction. Determination of EGFR protein expression was done by immunohistochemistry( IHC (Zymed, Laboratories. Fluorescence in situ hybridization (FISH was performed with LSI EGFR/CEP 7 (Vysis; Abbott Molecular, USA. Genomic DNA was extracted from 48 cases and exon 19 was amplified by polymerase chain reaction (PCR for search deletions and point mutations for exon 21. All cases expressed high weigh cytokeratin and were observed negativity for CK7, CD56 and chromogranin. Results: EGFR protein overexpression was identified in 49 cases, by the application of Hirsh’s scoring system. The chromosome 7 and EGFR gene were analyzed by FISH and scored according to Cappuzzo’s method that showed high polysomy in 31 cases and amplification in 7 cases. Deletion in exon 19 of EGFR was detected in 3 cases of 48 samples; the exon 21 of EGFR was expressed in its wild type by RFLP in all cases. Conclusions: Detection of common EGFR deletion and mutation showed to be a rare event in Squamous cell carcinoma of the lung. While EGFR mutation is the most effective molecular predictor or sensitivity in patients with advanced NSCLC submitted to EGFR-TKIs treatment, amplification and polysomy is the most effective molecular predictor for EGFR-TKIs responsiveness in squamous cell carcinoma, when valida ted isolated from the group of NSCLC.Objectivo: O receptor do

  1. 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

  2. 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.

  3. Gene doping in sports.

    Science.gov (United States)

    Unal, Mehmet; Ozer Unal, Durisehvar

    2004-01-01

    Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement. Copyright 2004 Adis Data Information BV

  4. Phylogenetic reconstruction of South American felids defined by protein electrophoresis

    OpenAIRE

    Pecon Slattery, J.; Johnson, W. E.; Goldman, D.; O'Brien, S. J.

    1994-01-01

    Phylogenetic associations among six closely related South American felid species were defined by changes in protein-encoding gene loci. We analyzed proteins isolated from skin fibroblasts using two-dimensional electrophoresis and allozymes extracted from blood cells. Genotypes were determined for multiple individuals of ocelot, margay, tigrina, Geoffroy's cat, kodkod, and pampas cat at 548 loci resolved by two-dimensional electrophoresis and 44 allozyme loci. Phenograms were constructed using...

  5. Indico CONFERENCE: Define the Call for Abstracts

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial, you will learn how to define and open a call for abstracts. When defining a call for abstracts, you will be able to define settings related to the type of questions asked during a review of an abstract, select the users who will review the abstracts, decide when to open the call for abstracts, and more.

  6. On defining semantics of extended attribute grammars

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    1980-01-01

    Knuth has introduced attribute grammars (AGs) as a tool to define the semanitcs of context-free languages. The use of AGs in connection with programming language definitions has mostly been to define the context-sensitive syntax of the language and to define a translation in code for a hypothetic...

  7. Languages for Software-Defined Networks

    Science.gov (United States)

    2013-02-01

    switches, firewalls, and middleboxes) with closed and proprietary configuration inter- faces. Software - Defined Networks ( SDN ) are poised to change...how- ever, have seen growing interest in software - defined networks ( SDNs ), in which a logically-centralized controller manages the packet-processing...switches, firewalls, and middleboxes) with closed and proprietary configuration interfaces. Software - Defined Networks ( SDN ) are poised to change this

  8. 22 CFR 92.36 - Authentication defined.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication defined. 92.36 Section 92.36... Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness of... recognized in another jurisdiction. Documents which may require authentication include legal instruments...

  9. A definability theorem for first order logic

    NARCIS (Netherlands)

    Butz, C.; Moerdijk, I.

    1997-01-01

    In this paper we will present a definability theorem for first order logic This theorem is very easy to state and its proof only uses elementary tools To explain the theorem let us first observe that if M is a model of a theory T in a language L then clearly any definable subset S M ie a subset S

  10. Dilution Confusion: Conventions for Defining a Dilution

    Science.gov (United States)

    Fishel, Laurence A.

    2010-01-01

    Two conventions for preparing dilutions are used in clinical laboratories. The first convention defines an "a:b" dilution as "a" volumes of solution A plus "b" volumes of solution B. The second convention defines an "a:b" dilution as "a" volumes of solution A diluted into a final volume of "b". Use of the incorrect dilution convention could affect…

  11. Defining Hardwood Veneer Log Quality Attributes

    Science.gov (United States)

    Jan Wiedenbeck; Michael Wiemann; Delton Alderman; John Baumgras; William Luppold

    2004-01-01

    This publication provides a broad spectrum of information on the hardwood veneer industry in North America. Veneer manufacturers and their customers impose guidelines in specifying wood quality attributes that are very discriminating but poorly defined (e.g., exceptional color, texture, and/or figure characteristics). To better understand and begin to define the most...

  12. Selective constraints in experimentally defined primate regulatory regions.

    Directory of Open Access Journals (Sweden)

    Daniel J Gaffney

    2008-08-01

    Full Text Available Changes in gene regulation may be important in evolution. However, the evolutionary properties of regulatory mutations are currently poorly understood. This is partly the result of an incomplete annotation of functional regulatory DNA in many species. For example, transcription factor binding sites (TFBSs, a major component of eukaryotic regulatory architecture, are typically short, degenerate, and therefore difficult to differentiate from randomly occurring, nonfunctional sequences. Furthermore, although sites such as TFBSs can be computationally predicted using evolutionary conservation as a criterion, estimates of the true level of selective constraint (defined as the fraction of strongly deleterious mutations occurring at a locus in regulatory regions will, by definition, be upwardly biased in datasets that are a priori evolutionarily conserved. Here we investigate the fitness effects of regulatory mutations using two complementary datasets of human TFBSs that are likely to be relatively free of ascertainment bias with respect to evolutionary conservation but, importantly, are supported by experimental data. The first is a collection of almost >2,100 human TFBSs drawn from the literature in the TRANSFAC database, and the second is derived from several recent high-throughput chromatin immunoprecipitation coupled with genomic microarray (ChIP-chip analyses. We also define a set of putative cis-regulatory modules (pCRMs by spatially clustering multiple TFBSs that regulate the same gene. We find that a relatively high proportion ( approximately 37% of mutations at TFBSs are strongly deleterious, similar to that at a 2-fold degenerate protein-coding site. However, constraint is significantly reduced in human and chimpanzee pCRMS and ChIP-chip sequences, relative to macaques. We estimate that the fraction of regulatory mutations that have been driven to fixation by positive selection in humans is not significantly different from zero. We also find

  13. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  14. Bilayer graphene quantum dot defined by topgates

    Energy Technology Data Exchange (ETDEWEB)

    Müller, André; Kaestner, Bernd; Hohls, Frank; Weimann, Thomas; Pierz, Klaus; Schumacher, Hans W., E-mail: hans.w.schumacher@ptb.de [Physikalisch-Technische Bundesanstalt, Bundesallee 100, 38116 Braunschweig (Germany)

    2014-06-21

    We investigate the application of nanoscale topgates on exfoliated bilayer graphene to define quantum dot devices. At temperatures below 500 mK, the conductance underneath the grounded gates is suppressed, which we attribute to nearest neighbour hopping and strain-induced piezoelectric fields. The gate-layout can thus be used to define resistive regions by tuning into the corresponding temperature range. We use this method to define a quantum dot structure in bilayer graphene showing Coulomb blockade oscillations consistent with the gate layout.

  15. Mapping Second Chromosome Mutations to Defined Genomic Regions in Drosophila melanogaster.

    Science.gov (United States)

    Kahsai, Lily; Cook, Kevin R

    2018-01-04

    Hundreds of Drosophila melanogaster stocks are currently maintained at the Bloomington Drosophila Stock Center with mutations that have not been associated with sequence-defined genes. They have been preserved because they have interesting loss-of-function phenotypes. The experimental value of these mutations would be increased by tying them to specific genomic intervals so that geneticists can more easily associate them with annotated genes. Here, we report the mapping of 85 second chromosome complementation groups in the Bloomington collection to specific, small clusters of contiguous genes or individual genes in the sequenced genome. This information should prove valuable to Drosophila geneticists interested in processes associated with particular phenotypes and those searching for mutations affecting specific sequence-defined genes. Copyright © 2018 Kahsai,Cook.

  16. Mapping Second Chromosome Mutations to Defined Genomic Regions in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    2018-01-01

    Full Text Available Hundreds of Drosophila melanogaster stocks are currently maintained at the Bloomington Drosophila Stock Center with mutations that have not been associated with sequence-defined genes. They have been preserved because they have interesting loss-of-function phenotypes. The experimental value of these mutations would be increased by tying them to specific genomic intervals so that geneticists can more easily associate them with annotated genes. Here, we report the mapping of 85 second chromosome complementation groups in the Bloomington collection to specific, small clusters of contiguous genes or individual genes in the sequenced genome. This information should prove valuable to Drosophila geneticists interested in processes associated with particular phenotypes and those searching for mutations affecting specific sequence-defined genes.

  17. Application-Defined Decentralized Access Control

    Science.gov (United States)

    Xu, Yuanzhong; Dunn, Alan M.; Hofmann, Owen S.; Lee, Michael Z.; Mehdi, Syed Akbar; Witchel, Emmett

    2014-01-01

    DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%–9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications’ security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

  18. Software Defined Multiband EVA Radio, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this research is to propose a reliable, lightweight, programmable, multi-band, multi-mode, miniaturized frequency-agile EVA software defined radio...

  19. Reconfigurable, Cognitive Software Defined Radio, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — IAI is actively developing Software Defined Radio platforms that can adaptively switch between different modes of operation by modifying both transmit waveforms and...

  20. Software Defined Multiband EVA Radio, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of Phase 2 is to build a reliable, lightweight, programmable, multi-mode, miniaturized EVA Software Defined Radio (SDR) that supports data telemetry,...

  1. Reconfigurable, Cognitive Software Defined Radio, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Intelligent Automation Inc, (IAI) is currently developing a software defined radio (SDR) platform that can adaptively switch between different modes of operation for...

  2. Optimum Criteria for Developing Defined Structures

    Directory of Open Access Journals (Sweden)

    Ion IVAN

    2008-01-01

    Full Text Available Basic aspects concerning distributed applications are presented: definition, particularities and importance. For distributed applications linear, arborescent, graph structures are defined with different versions and aggregation methods. Distributed applications have associated structures which through their characteristics influence the costs of the stages in the development cycle and the exploitation costs transferred to each user. The complexity of the defined structures is analyzed. The minimum and maximum criteria are enumerated for optimizing distributed application structures.

  3. Identification of differentiation-stage specific markers that define the ex vivo osteoblastic phenotype

    DEFF Research Database (Denmark)

    Twine, Natalie A; Chen, Li; Pang, Chi N

    2014-01-01

    The phenotype of osteoblastic (OB) cells in culture is currently defined using a limited number of markers of low sensitivity and specificity. For the clinical use of human skeletal (stromal, mesenchymal) stem cells (hMSC) in therapy, there is also a need to identify a set of gene markers...... clustering and Pearson's correlation generated 4 groups of genes: early stage differentiation genes (peak expression: 0-24h, n=28) which were enriched for extracellular matrix organisation, e.g. COL1A1, LOX, and SERPINH1; middle stage differentiating genes (peak expression days: 3 and 6, n=20) which were...

  4. Deficient motion-defined and texture-defined figure-ground segregation in amblyopic children.

    Science.gov (United States)

    Wang, Jane; Ho, Cindy S; Giaschi, Deborah E

    2007-01-01

    Motion-defined form deficits in the fellow eye and the amblyopic eye of children with amblyopia implicate possible direction-selective motion processing or static figure-ground segregation deficits. Deficient motion-defined form perception in the fellow eye of amblyopic children may not be fully accounted for by a general motion processing deficit. This study investigates the contribution of figure-ground segregation deficits to the motion-defined form perception deficits in amblyopia. Performances of 6 amblyopic children (5 anisometropic, 1 anisostrabismic) and 32 control children with normal vision were assessed on motion-defined form, texture-defined form, and global motion tasks. Performance on motion-defined and texture-defined form tasks was significantly worse in amblyopic children than in control children. Performance on global motion tasks was not significantly different between the 2 groups. Faulty figure-ground segregation mechanisms are likely responsible for the observed motion-defined form perception deficits in amblyopia.

  5. Doublecortin May Play a Role in Defining Chondrocyte Phenotype

    Directory of Open Access Journals (Sweden)

    Dongxia Ge

    2014-04-01

    Full Text Available Embryonic development of articular cartilage has not been well understood and the role of doublecortin (DCX in determination of chondrocyte phenotype is unknown. Here, we use a DCX promoter-driven eGFP reporter mouse model to study the dynamic gene expression profiles in mouse embryonic handplates at E12.5 to E13.5 when the condensed mesenchymal cells differentiate into either endochondral chondrocytes or joint interzone cells. Illumina microarray analysis identified a variety of genes that were expressed differentially in the different regions of mouse handplate. The unique expression patterns of many genes were revealed. Cytl1 and 3110032G18RIK were highly expressed in the proximal region of E12.5 handplate and the carpal region of E13.5 handplate, whereas Olfr538, Kctd15, and Cited1 were highly expressed in the distal region of E12.5 and the metacarpal region of E13.5 handplates. There was an increasing gradient of Hrc expression in the proximal to distal direction in E13.5 handplate. Furthermore, when human DCX protein was expressed in human adipose stem cells, collagen II was decreased while aggrecan, matrilin 2, and GDF5 were increased during the 14-day pellet culture. These findings suggest that DCX may play a role in defining chondrocyte phenotype.

  6. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  7. Hanford defined waste model limitations and improvements

    International Nuclear Information System (INIS)

    HARMSEN, R.W.

    1999-01-01

    Recommendation 93-5 Implementation Plan, Milestone 5,6.3.1.i requires issuance of this report which addresses ''updates to the tank contents model''. This report summarizes the review of the Hanford Defined Waste, Revision 4, model limitations and provides conclusions and recommendations for potential updates to the model

  8. Parallel Education and Defining the Fourth Sector.

    Science.gov (United States)

    Chessell, Diana

    1996-01-01

    Parallel to the primary, secondary, postsecondary, and adult/community education sectors is education not associated with formal programs--learning in arts and cultural sites. The emergence of cultural and educational tourism is an opportunity for adult/community education to define itself by extending lifelong learning opportunities into parallel…

  9. Bruxism defined and graded: an international consensus

    NARCIS (Netherlands)

    Lobbezoo, F.; Ahlberg, J.; Glaros, A.G.; Kato, T.; Koyano, K.; Lavigne, G.J.; de Leeuw, R.; Manfredini, D.; Svensson, P.; Winocur, E.

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined

  10. 7 CFR 28.950 - Terms defined.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., TESTING, AND STANDARDS Cotton Fiber and Processing Tests Definitions § 28.950 Terms defined. As used... Agricultural Marketing Service of the U.S. Department of Agriculture. (c) Administrator. The Administrator of...

  11. 47 CFR 54.401 - Lifeline defined.

    Science.gov (United States)

    2010-10-01

    ... SERVICE Universal Service Support for Low-Income Consumers § 54.401 Lifeline defined. (a) As used in this subpart, Lifeline means a retail local service offering: (1) That is available only to qualifying low-income consumers; (2) For which qualifying low-income consumers pay reduced charges as a result of...

  12. How Should Energy Be Defined throughout Schooling?

    Science.gov (United States)

    Bächtold, Manuel

    2018-01-01

    The question of how to teach energy has been renewed by recent studies focusing on the learning and teaching progressions for this concept. In this context, one question has been, for the most part, overlooked: how should energy be defined throughout schooling? This paper addresses this question in three steps. We first identify and discuss two…

  13. Big data and software defined networks

    CERN Document Server

    Taheri, Javid

    2018-01-01

    Big Data Analytics and Software Defined Networking (SDN) are helping to drive the management of data usage of the extraordinary increase of computer processing power provided by Cloud Data Centres (CDCs). This new book investigates areas where Big-Data and SDN can help each other in delivering more efficient services.

  14. 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...

  15. Towards a Southern African English Defining Vocabulary

    African Journals Online (AJOL)

    user

    of parameters, such as avoiding synonyms and antonyms, to determine which words are necessary to write definitions in a concise and simple way. It has been found that existing defining vocabularies lack certain words that would make definitions more accessible to southern African learners, and therefore there is a need ...

  16. 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.

  17. Pointwise extensions of GSOS-defined operations

    NARCIS (Netherlands)

    Hansen, H.H.; Klin, B.

    2011-01-01

    Final coalgebras capture system behaviours such as streams, infinite trees and processes. Algebraic operations on a final coalgebra can be defined by distributive laws (of a syntax functor S over a behaviour functor F). Such distributive laws correspond to abstract specification formats. One such

  18. Pointwise Extensions of GSOS-Defined Operations

    NARCIS (Netherlands)

    H.H. Hansen (Helle); B. Klin

    2011-01-01

    textabstractFinal coalgebras capture system behaviours such as streams, infinite trees and processes. Algebraic operations on a final coalgebra can be defined by distributive laws (of a syntax functor $\\FSig$ over a behaviour functor $F$). Such distributive laws correspond to abstract specification

  19. Defining Virtual Reality: Dimensions Determining Telepresence.

    Science.gov (United States)

    Steuer, Jonathan

    1992-01-01

    Defines virtual reality as a particular type of experience (in terms of "presence" and "telepresence") rather than as a collection of hardware. Maintains that media technologies can be classified and studied in terms of vividness and interactivity, two attributes on which virtual reality ranks very high. (SR)

  20. A self-defining hierarchical data system

    Science.gov (United States)

    Bailey, J.

    1992-01-01

    The Self-Defining Data System (SDS) is a system which allows the creation of self-defining hierarchical data structures in a form which allows the data to be moved between different machine architectures. Because the structures are self-defining they can be used for communication between independent modules in a distributed system. Unlike disk-based hierarchical data systems such as Starlink's HDS, SDS works entirely in memory and is very fast. Data structures are created and manipulated as internal dynamic structures in memory managed by SDS itself. A structure may then be exported into a caller supplied memory buffer in a defined external format. This structure can be written as a file or sent as a message to another machine. It remains static in structure until it is reimported into SDS. SDS is written in portable C and has been run on a number of different machine architectures. Structures are portable between machines with SDS looking after conversion of byte order, floating point format, and alignment. A Fortran callable version is also available for some machines.

  1. Metabolic profiles to define the genome: can we hear the phenotypes?

    OpenAIRE

    Griffin, Julian L

    2004-01-01

    There is an increased reliance on genetically modified organisms as a functional genomic tool to elucidate the role of genes and their protein products. Despite this, many models do not express the expected phenotype thought to be associated with the gene or protein. There is thus an increased need to further define the phenotype resultant from a genetic modification to understand how the transcriptional or proteomic network may conspire to alter the expected phenotype. This is best typified ...

  2. Defining Tiger Parenting in Chinese Americans.

    Science.gov (United States)

    Kim, Su Yeong

    2013-09-01

    "Tiger" parenting, as described by Amy Chua [2011], has instigated scholarly discourse on this phenomenon and its possible effects on families. Our eight-year longitudinal study, published in the Asian American Journal of Psychology [Kim, Wang, Orozco-Lapray, Shen, & Murtuza, 2013b], demonstrates that tiger parenting is not a common parenting profile in a sample of 444 Chinese American families. Tiger parenting also does not relate to superior academic performance in children. In fact, the best developmental outcomes were found among children of supportive parents. We examine the complexities around defining tiger parenting by reviewing classical literature on parenting styles and scholarship on Asian American parenting, along with Amy Chua's own description of her parenting method, to develop, define, and categorize variability in parenting in a sample of Chinese American families. We also provide evidence that supportive parenting is important for the optimal development of Chinese American adolescents.

  3. Defining enthesitis in spondyloarthritis by ultrasound

    DEFF Research Database (Denmark)

    Terslev, Lene; Naredo, E; Iagnocco, A

    2014-01-01

    Objective: To standardize ultrasound (US) in enthesitis. Methods: An Initial Delphi exercise was undertaken to define US detected enthesitis and its core components. These definitions were subsequently tested on static images taken from Spondyloarthritis (SpA) patients in order to evaluate...... elementary component. On static images the intra-observer reliability showed a high degree of variability for the detection of elementary lesions with kappa coefficients ranging from 0.14 - 1. The inter-observer kappa value was variable with the lowest kappa for enthesophytes (0.24) and the best for Doppler...... activity at the enthesis (0.63). Conclusion: This is the first consensus based definition of US enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work. Defining Enthesitis...

  4. Control of System with Defined Risk Level

    Directory of Open Access Journals (Sweden)

    Pavol Tomasov

    2002-01-01

    Full Text Available In the following paper the basic requirements for system control with defined risk level is presented. The paper should be an introduction to describe of theoretical apparatus, which was created during some years of research work in the Department of information and safety systems in this area. It a modification or creation of new parts of Information theory, System theory, and Control theory means. This parts are necessary for the analysis and synthesis tasks in the systems where dominant attribute of control is defined risk level. The basic problem is the creation of protect mechanism again the threats from inside and from controlled system environs. For each risk reduction mechanism is needed some redundancy which should be into control algorithm to put by exactly determined way.

  5. FINANCIAL ACCOUNTING QUALITY AND ITS DEFINING CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    Andra M. ACHIM

    2014-11-01

    Full Text Available The importance ofhigh-quality financial statements is highlighted by the main standard-setting institutions activating in the field of accounting and reporting. These have issued Conceptual Frameworks which state and describe the qualitative characteristics of accounting information. In this qualitative study, the research methodology consists of reviewing the literature related to the definition of accounting quality and striving for understanding how it can be explained. The main objective of the study is to identify the characteristics information should possess in order to be of high quality. These characteristics also contribute to the way of defining financial accounting quality. The main conclusions that arise from this research are represented by the facts that indeed financial accounting quality cannot be uniquely defined and that financial information is of good quality when it enhances the characteristics incorporated in the conceptual frameworks issued by both International Accounting Standards Board and Financial Accounting Standards Board.

  6. Exploring self-defining memories in schizophrenia.

    Science.gov (United States)

    Raffard, Stéphane; D'Argembeau, Arnaud; Lardi, Claudia; Bayard, Sophie; Boulenger, Jean-Philippe; Van Der Linden, Martial

    2009-01-01

    Previous studies have shown that patients with schizophrenia are impaired in recalling specific events from their personal past. However, the relationship between autobiographical memory impairments and disturbance of the sense of identity in schizophrenia has not been investigated in detail. In this study the authors investigated schizophrenic patients' ability to recall self-defining memories; that is, memories that play an important role in building and maintaining the self-concept. Results showed that patients recalled as many specific self-defining memories as healthy participants. However, patients with schizophrenia exhibited an abnormal reminiscence bump and reported different types of thematic content (i.e., they recalled less memories about past achievements and more memories regarding hospitalisation and stigmatisation of illness). Furthermore, the findings suggest that impairments in extracting meaning from personal memories could represent a core disturbance of autobiographical memory in patients with schizophrenia.

  7. Improving network management with Software Defined Networking

    International Nuclear Information System (INIS)

    Dzhunev, Pavel

    2013-01-01

    Software-defined networking (SDN) is developed as an alternative to closed networks in centers for data processing by providing a means to separate the control layer data layer switches, and routers. SDN introduces new possibilities for network management and configuration methods. In this article, we identify problems with the current state-of-the-art network configuration and management mechanisms and introduce mechanisms to improve various aspects of network management

  8. Stateless multicast switching in software defined networks

    OpenAIRE

    Reed, Martin J.; Al-Naday, Mays; Thomos, Nikolaos; Trossen, Dirk; Petropoulos, George; Spirou, Spiros

    2016-01-01

    Multicast data delivery can significantly reduce traffic in operators' networks, but has been limited in deployment due to concerns such as the scalability of state management. This paper shows how multicast can be implemented in contemporary software defined networking (SDN) switches, with less state than existing unicast switching strategies, by utilising a Bloom Filter (BF) based switching technique. Furthermore, the proposed mechanism uses only proactive rule insertion, and thus, is not l...

  9. Defining and Distinguishing Traditional and Religious Terrorism

    OpenAIRE

    Gregg, Heather S.

    2014-01-01

    The article of record may be found at: http://dx.doi.org/10.1080/23296151.2016.1239978 thus offering few if any policy options for counterterrorism measures. This assumption about religious terrorism stems from two challenges in the literature: disproportionate attention to apocalyptic terrorism, and a lack of distinction between religious terrorism and its secular counterpart. This article, therefore, aims to do four things: define and differentiate religiously motivated terrorism from tr...

  10. Defining Trust Using Expected Utility Theory

    OpenAIRE

    Arai, Kazuhiro

    2009-01-01

    Trust has been discussed in many social sciences including economics, psychology, and sociology. However, there is no widely accepted definition of trust. Inparticular, there is no definition that can be used for economic analysis. This paper regards trust as expectation and defines it using expected utility theory together with concepts such as betrayal premium. In doing so, it rejects the widely accepted black-and-white view that (un) trustworthy people are always (un)trustworthy. This pape...

  11. 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...

  12. How Should Energy Be Defined Throughout Schooling?

    Science.gov (United States)

    Bächtold, Manuel

    2017-02-01

    The question of how to teach energy has been renewed by recent studies focusing on the learning and teaching progressions for this concept. In this context, one question has been, for the most part, overlooked: how should energy be defined throughout schooling? This paper addresses this question in three steps. We first identify and discuss two main approaches in physics concerning the definition of energy, one claiming there is no satisfactory definition and taking conservation as a fundamental property, and the other based on Rankine's definition of energy as the capacity of a system to produce changes. We then present a study concerning how energy is actually defined throughout schooling in the case of France by analyzing national programs, physics textbooks, and the answers of teachers to a questionnaire. This study brings to light a consistency problem in the way energy is defined across school years: in primary school, an adapted version of Rankine's definition is introduced and conservation is ignored; in high school, conservation is introduced and Rankine's definition is ignored. Finally, we address this consistency problem by discussing possible teaching progressions. We argue in favor of the use of Rankine's definition throughout schooling: at primary school, it is a possible substitute to students' erroneous conceptions; at secondary school, it might help students become aware of the unifying role of energy and thereby overcome the compartmentalization problem.

  13. Defining behavioral and molecular differences between summer and migratory monarch butterflies

    Science.gov (United States)

    Zhu, Haisun; Gegear, Robert J; Casselman, Amy; Kanginakudru, Sriramana; Reppert, Steven M

    2009-01-01

    Background In the fall, Eastern North American monarch butterflies (Danaus plexippus) undergo a magnificent long-range migration. In contrast to spring and summer butterflies, fall migrants are juvenile hormone deficient, which leads to reproductive arrest and increased longevity. Migrants also use a time-compensated sun compass to help them navigate in the south/southwesterly direction en route for Mexico. Central issues in this area are defining the relationship between juvenile hormone status and oriented flight, critical features that differentiate summer monarchs from fall migrants, and identifying molecular correlates of behavioral state. Results Here we show that increasing juvenile hormone activity to induce summer-like reproductive development in fall migrants does not alter directional flight behavior or its time-compensated orientation, as monitored in a flight simulator. Reproductive summer butterflies, in contrast, uniformly fail to exhibit directional, oriented flight. To define molecular correlates of behavioral state, we used microarray analysis of 9417 unique cDNA sequences. Gene expression profiles reveal a suite of 40 genes whose differential expression in brain correlates with oriented flight behavior in individual migrants, independent of juvenile hormone activity, thereby molecularly separating fall migrants from summer butterflies. Intriguing genes that are differentially regulated include the clock gene vrille and the locomotion-relevant tyramine beta hydroxylase gene. In addition, several differentially regulated genes (37.5% of total) are not annotated. We also identified 23 juvenile hormone-dependent genes in brain, which separate reproductive from non-reproductive monarchs; genes involved in longevity, fatty acid metabolism, and innate immunity are upregulated in non-reproductive (juvenile-hormone deficient) migrants. Conclusion The results link key behavioral traits with gene expression profiles in brain that differentiate migratory

  14. Defining operational taxonomic units using DNA barcode data.

    Science.gov (United States)

    Blaxter, Mark; Mann, Jenna; Chapman, Tom; Thomas, Fran; Whitton, Claire; Floyd, Robin; Abebe, Eyualem

    2005-10-29

    The scale of diversity of life on this planet is a significant challenge for any scientific programme hoping to produce a complete catalogue, whatever means is used. For DNA barcoding studies, this difficulty is compounded by the realization that any chosen barcode sequence is not the gene 'for' speciation and that taxa have evolutionary histories. How are we to disentangle the confounding effects of reticulate population genetic processes? Using the DNA barcode data from meiofaunal surveys, here we discuss the benefits of treating the taxa defined by barcodes without reference to their correspondence to 'species', and suggest that using this non-idealist approach facilitates access to taxon groups that are not accessible to other methods of enumeration and classification. Major issues remain, in particular the methodologies for taxon discrimination in DNA barcode data.

  15. Genome assortment, not serogroup, defines Vibrio cholerae pandemic strains

    Energy Technology Data Exchange (ETDEWEB)

    Brettin, Thomas S [Los Alamos National Laboratory; Bruce, David C [Los Alamos National Laboratory; Challacombe, Jean F [Los Alamos National Laboratory; Detter, John C [Los Alamos National Laboratory; Han, Cliff S [Los Alamos National Laboratory; Munik, A C [Los Alamos National Laboratory; Chertkov, Olga [Los Alamos National Laboratory; Meincke, Linda [Los Alamos National Laboratory; Saunders, Elizabeth [Los Alamos National Laboratory; Choi, Seon Y [SEOUL NATL. UNIV.; Haley, Bradd J [U. MARYLAND; Taviani, Elisa [U. MARYLAND; Jeon, Yoon - Seong [INTL. VACCINE INST. SEOUL; Kim, Dong Wook [INTL. VACCINE INST. SEOUL; Lee, Jae - Hak [SEOUL NATL. UNIV.; Walters, Ronald A [PNNL; Hug, Anwar [NATL. INST. CHOLERIC ENTERIC DIS.; Colwell, Rita R [U. MARYLAND

    2009-01-01

    Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the 6th and the current 7th pandemics, respectively. Cholera researchers continually face newly emerging and re-emerging pathogenic clones carrying combinations of new serogroups as well as of phenotypic and genotypic properties. These genotype and phenotype changes have hampered control of the disease. Here we compare the complete genome sequences of 23 strains of V. cholerae isolated from a variety of sources and geographical locations over the past 98 years in an effort to elucidate the evolutionary mechanisms governing genetic diversity and genesis of new pathogenic clones. The genome-based phylogeny revealed 12 distinct V. cholerae phyletic lineages, of which one, designated the V. cholerae core genome (CG), comprises both O1 classical and EI Tor biotypes. All 7th pandemic clones share nearly identical gene content, i.e., the same genome backbone. The transition from 6th to 7th pandemic strains is defined here as a 'shift' between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages within the CG clade. In contrast, transition among clones during the present 7th pandemic period can be characterized as a 'drift' between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V.cholerae serogroup O139 and V.cholerae O1 El Tor hybrid clones that produce cholera toxin of classical biotype. Based on the comprehensive comparative genomics presented in this study it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to

  16. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M

    2008-10-01

    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  17. The Caenorhabditis chemoreceptor gene families.

    Science.gov (United States)

    Thomas, James H; Robertson, Hugh M

    2008-10-06

    Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  18. Defining the biological bases of individual differences in musicality.

    Science.gov (United States)

    Gingras, Bruno; Honing, Henkjan; Peretz, Isabelle; Trainor, Laurel J; Fisher, Simon E

    2015-03-19

    Advances in molecular technologies make it possible to pinpoint genomic factors associated with complex human traits. For cognition and behaviour, identification of underlying genes provides new entry points for deciphering the key neurobiological pathways. In the past decade, the search for genetic correlates of musicality has gained traction. Reports have documented familial clustering for different extremes of ability, including amusia and absolute pitch (AP), with twin studies demonstrating high heritability for some music-related skills, such as pitch perception. Certain chromosomal regions have been linked to AP and musical aptitude, while individual candidate genes have been investigated in relation to aptitude and creativity. Most recently, researchers in this field started performing genome-wide association scans. Thus far, studies have been hampered by relatively small sample sizes and limitations in defining components of musicality, including an emphasis on skills that can only be assessed in trained musicians. With opportunities to administer standardized aptitude tests online, systematic large-scale assessment of musical abilities is now feasible, an important step towards high-powered genome-wide screens. Here, we offer a synthesis of existing literatures and outline concrete suggestions for the development of comprehensive operational tools for the analysis of musical phenotypes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  19. Defining the biological bases of individual differences in musicality

    Science.gov (United States)

    Gingras, Bruno; Honing, Henkjan; Peretz, Isabelle; Trainor, Laurel J.; Fisher, Simon E.

    2015-01-01

    Advances in molecular technologies make it possible to pinpoint genomic factors associated with complex human traits. For cognition and behaviour, identification of underlying genes provides new entry points for deciphering the key neurobiological pathways. In the past decade, the search for genetic correlates of musicality has gained traction. Reports have documented familial clustering for different extremes of ability, including amusia and absolute pitch (AP), with twin studies demonstrating high heritability for some music-related skills, such as pitch perception. Certain chromosomal regions have been linked to AP and musical aptitude, while individual candidate genes have been investigated in relation to aptitude and creativity. Most recently, researchers in this field started performing genome-wide association scans. Thus far, studies have been hampered by relatively small sample sizes and limitations in defining components of musicality, including an emphasis on skills that can only be assessed in trained musicians. With opportunities to administer standardized aptitude tests online, systematic large-scale assessment of musical abilities is now feasible, an important step towards high-powered genome-wide screens. Here, we offer a synthesis of existing literatures and outline concrete suggestions for the development of comprehensive operational tools for the analysis of musical phenotypes. PMID:25646515

  20. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

    Science.gov (United States)

    Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2017-09-01

    Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

  1. Defining Multiple Chronic Conditions for Quality Measurement.

    Science.gov (United States)

    Drye, Elizabeth E; Altaf, Faseeha K; Lipska, Kasia J; Spatz, Erica S; Montague, Julia A; Bao, Haikun; Parzynski, Craig S; Ross, Joseph S; Bernheim, Susannah M; Krumholz, Harlan M; Lin, Zhenqiu

    2018-02-01

    Patients with multiple chronic conditions (MCCs) are a critical but undefined group for quality measurement. We present a generally applicable systematic approach to defining an MCC cohort of Medicare fee-for-service beneficiaries that we developed for a national quality measure, risk-standardized rates of unplanned admissions for Accountable Care Organizations. To define the MCC cohort we: (1) identified potential chronic conditions; (2) set criteria for cohort conditions based on MCC framework and measure concept; (3) applied the criteria informed by empirical analysis, experts, and the public; (4) described "broader" and "narrower" cohorts; and (5) selected final cohort with stakeholder input. Subjects were patients with chronic conditions. Participants included 21.8 million Medicare fee-for-service beneficiaries in 2012 aged 65 years and above with ≥1 of 27 Medicare Chronic Condition Warehouse condition(s). In total, 10 chronic conditions were identified based on our criteria; 8 of these 10 were associated with notably increased admission risk when co-occurring. A broader cohort (2+ of the 8 conditions) included 4.9 million beneficiaries (23% of total cohort) with an admission rate of 70 per 100 person-years. It captured 53% of total admissions. The narrower cohort (3+ conditions) had 2.2 million beneficiaries (10%) with 100 admissions per 100 person-years and captured 32% of admissions. Most stakeholders viewed the broader cohort as best aligned with the measure concept. By systematically narrowing chronic conditions to those most relevant to the outcome and incorporating stakeholder input, we defined an MCC admission measure cohort supported by stakeholders. This approach can be used as a model for other MCC outcome measures.

  2. How do pediatric anesthesiologists define intraoperative hypotension?

    Science.gov (United States)

    Nafiu, Olubukola O; Voepel-Lewis, Terri; Morris, Michelle; Chimbira, Wilson T; Malviya, Shobha; Reynolds, Paul I; Tremper, Kevin K

    2009-11-01

    Although blood pressure (BP) monitoring is a recommended standard of care by the ASA, and pediatric anesthesiologists routinely monitor the BP of their patients and when appropriate treat deviations from 'normal', there is no robust definition of hypotension in any of the pediatric anesthesia texts or journals. Consequently, what constitutes hypotension in pediatric anesthesia is currently unknown. We designed a questionnaire-based survey of pediatric anesthesiologists to determine the BP ranges and thresholds used to define intraoperative hypotension (IOH). Members of the Society of Pediatric Anesthesia (SPA) and the Association of Paediatric Anaesthetists (APA) of Great Britain and Ireland were contacted through e-mail to participate in this survey. We asked a few demographic questions and five questions about specific definitions of hypotension for different age groups of patients undergoing inguinal herniorraphy, a common pediatric surgical procedure. The overall response rate was 56% (483/860), of which 76% were SPA members. Majority of the respondents (72%) work in academic institutions, while 8.9% work in institutions with fewer than 1000 annual pediatric surgical caseload. About 76% of respondents indicated that a 20-30% reduction in baseline systolic blood pressure (SBP) indicates significant hypotension in children under anesthesia. Most responders (86.7%) indicated that they use mean arterial pressure or SBP (72%) to define IOH. The mean SBP values for hypotension quoted by SPA members was about 5-7% lower across all pediatric age groups compared to values quoted by APA members (P = 0.001 for all age groups). There is great variability in the BP parameters used and the threshold used for defining and treating IOH among pediatric anesthesiologists. The majority of respondents considered a 20-30% reduction from baseline in SBP as indicative of significant hypotension. Lack of a consensus definition for a common clinical condition like IOH could have

  3. Defining recovery in adult bulimia nervosa.

    Science.gov (United States)

    Yu, Jessica; Agras, W Stewart; Bryson, Susan

    2013-01-01

    To examine how different definitions of recovery lead to varying rates of recovery, maintenance of recovery, and relapse in bulimia nervosa (BN), end-of-treatment (EOT) and follow-up data were obtained from 96 adults with BN. Combining behavioral, physical, and psychological criteria led to recovery rates between 15.5% and 34.4% at EOT, though relapse was approximately 50%. Combining these criteria and requiring abstinence from binge eating and purging when defining recovery may lead to lower recovery rates than those found in previous studies; however, a strength of this definition is that individuals who meet this criteria have no remaining disordered behaviors or symptoms.

  4. Defining Marriage: Classification, Interpretation, and Definitional Disputes

    Directory of Open Access Journals (Sweden)

    Fabrizio Macagno

    2016-09-01

    Full Text Available The classification of a state of affairs under a legal category can be considered as a kind of con- densed decision that can be made explicit, analyzed, and assessed us- ing argumentation schemes. In this paper, the controversial conflict of opinions concerning the nature of “marriage” in Obergefell v. Hodges is analyzed pointing out the dialecti- cal strategies used for addressing the interpretive doubts. The dispute about the same-sex couples’ right to marry hides a much deeper disa- greement not only about what mar- riage is, but more importantly about the dialectical rules for defining it.

  5. Software defined networks a comprehensive approach

    CERN Document Server

    Goransson, Paul

    2014-01-01

    Software Defined Networks discusses the historical networking environment that gave rise to SDN, as well as the latest advances in SDN technology. The book gives you the state of the art knowledge needed for successful deployment of an SDN, including: How to explain to the non-technical business decision makers in your organization the potential benefits, as well as the risks, in shifting parts of a network to the SDN modelHow to make intelligent decisions about when to integrate SDN technologies in a networkHow to decide if your organization should be developing its own SDN applications or

  6. Software Defined Radio: Basic Principles and Applications

    Directory of Open Access Journals (Sweden)

    José Raúl Machado-Fernández

    2014-12-01

    Full Text Available The author makes a review of the SDR (Software Defined Radio technology, including hardware schemes and application fields. A low performance device is presented and several tests are executed with it using free software. With the acquired experience, SDR employment opportunities are identified for low-cost solutions that can solve significant problems. In addition, a list of the most important frameworks related to the technology developed in the last years is offered, recommending the use of three of them.

  7. Defining the Strategy of Nuclear Activity

    International Nuclear Information System (INIS)

    Racana, R.

    2006-01-01

    This article presents nuclear activity as defined within the field of the nuclear industry, which is studied from its capacity to generate electric power to its application in industry and medicine as well as a source for weapons of mass destruction. These fields of analysis introduce some problems that the nuclear activity itself must know how to confront employing action strategies aimed at becoming an activity to be kept in mind when making use of the benefits that its peaceful use contributes to human life. (Author)

  8. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  9. DEFINING THE CHEMICAL SPACE OF PUBLIC GENOMIC ...

    Science.gov (United States)

    The current project aims to chemically index the genomics content of public genomic databases to make these data accessible in relation to other publicly available, chemically-indexed toxicological information. By defining the chemical space of public genomic data, it is possible to identify classes of chemicals on which to develop methodologies for the integration of chemogenomic data into predictive toxicology. The chemical space of public genomic data will be presented as well as the methodologies and tools developed to identify this chemical space.

  10. Healthcare Engineering Defined: A White Paper.

    Science.gov (United States)

    Chyu, Ming-Chien; Austin, Tony; Calisir, Fethi; Chanjaplammootil, Samuel; Davis, Mark J; Favela, Jesus; Gan, Heng; Gefen, Amit; Haddas, Ram; Hahn-Goldberg, Shoshana; Hornero, Roberto; Huang, Yu-Li; Jensen, Øystein; Jiang, Zhongwei; Katsanis, J S; Lee, Jeong-A; Lewis, Gladius; Lovell, Nigel H; Luebbers, Heinz-Theo; Morales, George G; Matis, Timothy; Matthews, Judith T; Mazur, Lukasz; Ng, Eddie Yin-Kwee; Oommen, K J; Ormand, Kevin; Rohde, Tarald; Sánchez-Morillo, Daniel; Sanz-Calcedo, Justo García; Sawan, Mohamad; Shen, Chwan-Li; Shieh, Jiann-Shing; Su, Chao-Ton; Sun, Lilly; Sun, Mingui; Sun, Yi; Tewolde, Senay N; Williams, Eric A; Yan, Chongjun; Zhang, Jiajie; Zhang, Yuan-Ting

    2015-01-01

    Engineering has been playing an important role in serving and advancing healthcare. The term "Healthcare Engineering" has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of "Healthcare Engineering" remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects.

  11. Software defined networking applications in distributed datacenters

    CERN Document Server

    Qi, Heng

    2016-01-01

    This SpringerBrief provides essential insights on the SDN application designing and deployment in distributed datacenters. In this book, three key problems are discussed: SDN application designing, SDN deployment and SDN management. This book demonstrates how to design the SDN-based request allocation application in distributed datacenters. It also presents solutions for SDN controller placement to deploy SDN in distributed datacenters. Finally, an SDN management system is proposed to guarantee the performance of datacenter networks which are covered and controlled by many heterogeneous controllers. Researchers and practitioners alike will find this book a valuable resource for further study on Software Defined Networking. .

  12. Defining Starch Binding by Glucan Phosphatases

    DEFF Research Database (Denmark)

    Auger, Kyle; Raththagala, Madushi; Wilkens, Casper

    2015-01-01

    Starch is a vital energy molecule in plants that has a wide variety of uses in industry, such as feedstock for biomaterial processing and biofuel production. Plants employ a three enzyme cyclic process utilizing kinases, amylases, and phosphatases to degrade starch in a diurnal manner. Starch...... is comprised of the branched glucan amylopectin and the more linear glucan amylose. Our lab has determined the first structures of these glucan phosphatases and we have defined their enzymatic action. Despite this progress, we lacked a means to quickly and efficiently quantify starch binding to glucan...

  13. Healthcare Engineering Defined: A White Paper

    Directory of Open Access Journals (Sweden)

    Ming-Chien Chyu

    2015-01-01

    Full Text Available Engineering has been playing an important role in serving and advancing healthcare. The term “Healthcare Engineering” has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of “Healthcare Engineering” remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects.

  14. 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.

  15. Fingerprinting Software Defined Networks and Controllers

    Science.gov (United States)

    2015-03-01

    rps requests per second RTT Round-Trip Time SDN Software Defined Networking SOM Self-Organizing Map STP Spanning Tree Protocol TRW-CB Threshold Random...Protocol ( STP ) updates), in which case the frame will be “punted” from the forwarding lookup process and processed by the route processor [9]. The act of...environment 20 to accomplish the needs of B4. In addition to Google, the SDN market is expected to grow beyond $35 billion by April 2018 [31]. The rate

  16. Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix

    NARCIS (Netherlands)

    Kersemaekers, A. M.; Hermans, J.; Fleuren, G. J.; van de Vijver, M. J.

    1998-01-01

    Loss of heterozygosity (LOH) frequently occurs in squamous cell carcinomas of the uterine cervix and indicates the probable sites of tumour-suppressor genes that play a role in the development of this tumour. To define the localization of these tumour-suppressor genes, we studied loss of

  17. Homology building as a means to define antigenic epitopes on dihydrofolate reductase (DHFR) from Plasmodium falciparum

    DEFF Research Database (Denmark)

    Alifrangis, Michael; Christensen, Inge T; Jørgensen, Flemming S

    2004-01-01

    in the gene coding for Pf-DHFR. Furthermore, we wanted to study the potential use of homology models in general and of Pf-DHFR in particular in predicting antigenic malarial surface epitopes. METHODS: A homology model of Pf-DHFR domain was employed to define an epitope for the development of site...

  18. Defining clogging potential for permeable concrete.

    Science.gov (United States)

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2018-08-15

    Permeable concrete is used to reduce urban flooding as it allows water to flow through normally impermeable infrastructure. It is prone to clogging by particulate matter and predicting the long-term performance of permeable concrete is challenging as there is currently no reliable means of characterising clogging potential. This paper reports on the performance of a range of laboratory-prepared and commercial permeable concretes, close packed glass spheres and aggregate particles of varying size, exposed to different clogging methods to understand this phenomena. New methods were developed to study clogging and define clogging potential. The tests involved applying flowing water containing sand and/or clay in cycles, and measuring the change in permeability. Substantial permeability reductions were observed in all samples, particularly when exposed to sand and clay simultaneously. Three methods were used to define clogging potential based on measuring the initial permeability decay, half-life cycle and number of cycles to full clogging. We show for the first time strong linear correlations between these parameters for a wide range of samples, indicating their use for service-life prediction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Defining an Open Source Strategy for NASA

    Science.gov (United States)

    Mattmann, C. A.; Crichton, D. J.; Lindsay, F.; Berrick, S. W.; Marshall, J. J.; Downs, R. R.

    2011-12-01

    Over the course of the past year, we have worked to help frame a strategy for NASA and open source software. This includes defining information processes to understand open source licensing, attribution, commerciality, redistribution, communities, architectures, and interactions within the agency. Specifically we held a training session at the NASA Earth Science Data Systems Working Group meeting in Open Source software as it relates to the NASA Earth Science data systems enterprise, including EOSDIS, the Distributed Active Archive Centers (DAACs), ACCESS proposals, and the MEASURES communities, and efforts to understand how open source software can be both consumed and produced within that ecosystem. In addition, we presented at the 1st NASA Open Source Summit (OSS) and helped to define an agency-level strategy, a set of recommendations and paths forward for how to identify healthy open source communities, how to deal with issues such as contributions originating from other agencies, and how to search out talent with the right skills to develop software for NASA in the modern age. This talk will review our current recommendations for open source at NASA, and will cover the set of thirteen recommendations output from the NASA Open Source Summit and discuss some of their implications for the agency.

  20. How Do You Define an Internship?

    Science.gov (United States)

    Wilson, C. E.; Keane, C.

    2017-12-01

    According to the American Geosciences Institute's Geoscience Student Exit Survey, internship participation rates over the past four years have been low, particularly among bachelor's and doctoral graduates. In 2016, 65% of bachelor's graduates, 44% of master's graduates, and 57% of doctoral graduates did not participate in an internship while working on their degree. When asked if they submitted applications for internship opportunities, 42% of bachelor's graduates, 23% of master's graduates, and 46% of doctoral graduates claimed to not submit any applications. These statistics have raised concern at AGI because internships provide experiences that help develop critical professional skills and industry connections that can lead to jobs after graduation. However, when internships are discussed among various representatives in geoscience industries, there are disagreements in how an internship experience is defined. For example, opinions differ on whether REUs or other research experiences count as an internship. Clear definitions of internship opportunities may help academic faculty and advisors direct students towards these opportunities and help develop a collection of resources for finding future internships. This presentation will present some of the recent statistics on internship participation among geoscience graduates and present a series of questions to ascertain defining features of internships among AGU attendees and where help is needed to increase participation in internships among current geoscience students.

  1. Defining Medical Capabilities for Exploration Missions

    Science.gov (United States)

    Hailey, M.; Antonsen, E.; Blue, R.; Reyes, D.; Mulcahy, R.; Kerstman, E.; Bayuse, T.

    2018-01-01

    Exploration-class missions to the moon, Mars and beyond will require a significant change in medical capability from today's low earth orbit centric paradigm. Significant increases in autonomy will be required due to differences in duration, distance and orbital mechanics. Aerospace medicine and systems engineering teams are working together within ExMC to meet these challenges. Identifying exploration medical system needs requires accounting for planned and unplanned medical care as defined in the concept of operations. In 2017, the ExMC Clinicians group identified medical capabilities to feed into the Systems Engineering process, including: determining what and how to address planned and preventive medical care; defining an Accepted Medical Condition List (AMCL) of conditions that may occur and a subset of those that can be treated effectively within the exploration environment; and listing the medical capabilities needed to treat those conditions in the AMCL. This presentation will discuss the team's approach to addressing these issues, as well as how the outputs of the clinical process impact the systems engineering effort.

  2. Distributed controller clustering in software defined networks.

    Directory of Open Access Journals (Sweden)

    Ahmed Abdelaziz

    Full Text Available Software Defined Networking (SDN is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN SDN and Open Network Operating System (ONOS controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability.

  3. Distributed controller clustering in software defined networks.

    Science.gov (United States)

    Abdelaziz, Ahmed; Fong, Ang Tan; Gani, Abdullah; Garba, Usman; Khan, Suleman; Akhunzada, Adnan; Talebian, Hamid; Choo, Kim-Kwang Raymond

    2017-01-01

    Software Defined Networking (SDN) is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs) brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN) SDN and Open Network Operating System (ONOS) controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability.

  4. Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.

    Science.gov (United States)

    Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian

    2018-02-23

    Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Defining Mapping Mashups with BioXMash

    Directory of Open Access Journals (Sweden)

    Hunt Ela

    2007-12-01

    Full Text Available We present a novel approach to XML data integration which allows a biologist to select data from a large XML file repository, add it to a genome map, and produce a mapping mashup showing integrated data in map context. This approach can be used to produce contextual views of arbitrary XML data which relates to objects shown on a map. A biologist using BioXMash searches in XML tags, and is guided by XML path data availability, shown as the number of values reachable via a path, in both global, genome-wide, and local, per-gene, context. Then she examines sample values in an area of interest on the map. If required, the resulting data is dumped to files, for subsequent analysis.

  6. 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.

  7. Nurse leader resilience: career defining moments.

    Science.gov (United States)

    Cline, Susan

    2015-01-01

    Resilience is an essential component of effective nursing leadership. It is defined as the ability to survive and thrive in the face of adversity. Resilience can be developed and internalized as a measure to improve retention and reduce burnout. Nurse leaders at all levels should develop these competencies to survive and thrive in an increasingly complex health care environment. Building positive relationships, maintaining positivity, developing emotional insight, creating work-life balance, and reflecting on successes and challenges are effective strategies for resilience building. Nurse leaders have a professional obligation to develop resilience in themselves, the teams they supervise, and the organization as a whole. Additional benefits include reduced turnover, reduced cost, and improved quality outcomes through organizational mindfulness.

  8. Defining and testing a granular continuum element

    Energy Technology Data Exchange (ETDEWEB)

    Rycroft, Chris H.; Kamrin, Ken; Bazant, Martin Z.

    2007-12-03

    Continuum mechanics relies on the fundamental notion of amesoscopic volume "element" in which properties averaged over discreteparticles obey deterministic relationships. Recent work on granularmaterials suggests a continuum law may be inapplicable, revealinginhomogeneities at the particle level, such as force chains and slow cagebreaking. Here, we analyze large-scale Discrete-Element Method (DEM)simulations of different granular flows and show that a "granularelement" can indeed be defined at the scale of dynamical correlations,roughly three to five particle diameters. Its rheology is rather subtle,combining liquid-like dependence on deformation rate and solid-likedependence on strain. Our results confirm some aspects of classicalplasticity theory (e.g., coaxiality of stress and deformation rate),while contradicting others (i.e., incipient yield), and can guide thedevelopment of more realistic continuum models.

  9. Defining and Distinguishing Secular and Religious Terrorism

    Directory of Open Access Journals (Sweden)

    Heather S. Gregg

    2014-04-01

    Full Text Available Religious terrorism is typically characterised as acts of unrestrained, irrational and indiscriminant violence, thus offering few if any policy options for counterterrorism measures. This assumption about religious terrorism stems from two challenges in the literature: disproportionate attention to apocalyptic terrorism, and a lack of distinction between religious terrorism and its secular counterpart. This article, therefore, aims to do four things: define and differentiate religiously motivated terrorism from traditional terrorism; investigate three goals of religious terrorism (fomenting the apocalypse, creating a religious government, and establishing a religiously pure state; consider the role of leadership and target selection of religious terrorists; and, finally, suggest a range of counterterrorism strategies based on these observations.

  10. "Defining Computer 'Speed': An Unsolved Challenge"

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    Abstract: The reason we use computers is their speed, and the reason we use parallel computers is that they're faster than single-processor computers. Yet, after 70 years of electronic digital computing, we still do not have a solid definition of what computer 'speed' means, or even what it means to be 'faster'. Unlike measures in physics, where the definition of speed is rigorous and unequivocal, in computing there is no definition of speed that is universally accepted. As a result, computer customers have made purchases misguided by dubious information, computer designers have optimized their designs for the wrong goals, and computer programmers have chosen methods that optimize the wrong things. This talk describes why some of the obvious and historical ways of defining 'speed' haven't served us well, and the things we've learned in the struggle to find a definition that works. Biography: Dr. John Gustafson is a Director ...

  11. Using archetypes for defining CDA templates.

    Science.gov (United States)

    Moner, David; Moreno, Alberto; Maldonado, José A; Robles, Montserrat; Parra, Carlos

    2012-01-01

    While HL7 CDA is a widely adopted standard for the documentation of clinical information, the archetype approach proposed by CEN/ISO 13606 and openEHR is gaining recognition as a means of describing domain models and medical knowledge. This paper describes our efforts in combining both standards. Using archetypes as an alternative for defining CDA templates permit new possibilities all based on the formal nature of archetypes and their ability to merge into the same artifact medical knowledge and technical requirements for semantic interoperability of electronic health records. We describe the process followed for the normalization of existing legacy data in a hospital environment, from the importation of the HL7 CDA model into an archetype editor, the definition of CDA archetypes and the application of those archetypes to obtain normalized CDA data instances.

  12. Defining the critical hurdles in cancer immunotherapy

    DEFF Research Database (Denmark)

    Fox, Bernard A; Schendel, Dolores J; Butterfield, Lisa H

    2011-01-01

    of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical...... immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation...... companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed...

  13. Just caring: defining a basic benefit package.

    Science.gov (United States)

    Fleck, Leonard M

    2011-12-01

    What should be the content of a package of health care services that we would want to guarantee to all Americans? This question cannot be answered adequately apart from also addressing the issue of fair health care rationing. Consequently, as I argue in this essay, appeal to the language of "basic," "essential," "adequate," "minimally decent," or "medically necessary" for purposes of answering our question is unhelpful. All these notions are too vague to be useful. Cost matters. Effectiveness matters. The clinical circumstances of a patient matters. But what we must ultimately determine is what we mutually agree are the just claims to needed health care of each American in a relatively complex range of clinical circumstances. Answering this question will require a public moral conversation, a fair process of rational democratic deliberation aimed at defining both just claims to needed health care and just limits.

  14. Bruxism defined and graded: an international consensus.

    Science.gov (United States)

    Lobbezoo, F; Ahlberg, J; Glaros, A G; Kato, T; Koyano, K; Lavigne, G J; de Leeuw, R; Manfredini, D; Svensson, P; Winocur, E

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined bruxism as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or during wakefulness (indicated as awake bruxism). For the operationalisation of this definition, the expert group proposes a diagnostic grading system of 'possible', 'probable' and 'definite' sleep or awake bruxism. The proposed definition and grading system are suggested for clinical and research purposes in all relevant dental and medical domains. © 2012 Blackwell Publishing Ltd.

  15. Defining and Supporting Narrative-driven Recommendation

    DEFF Research Database (Denmark)

    Bogers, Toine; Koolen, Marijn

    2017-01-01

    Research into recommendation algorithms has made great strides in recent years. However, these algorithms are typically applied in relatively straightforward scenarios: given information about a user's past preferences, what will they like in the future? Recommendation is often more complex......: evaluating recommended items never takes place in a vacuum, and it is often a single step in the user's more complex background task. In this paper, we define a specific type of recommendation scenario called narrative-driven recommendation, where the recommendation process is driven by both a log...... of the user's past transactions as well as a narrative description of their current interest(s). Through an analysis of a set of real-world recommendation narratives from the LibraryThing forums, we demonstrate the uniqueness and richness of this scenario and highlight common patterns and properties...

  16. Defining Service and Education in Pediatrics.

    Science.gov (United States)

    Boyer, Debra; Gagne, Josh; Kesselheim, Jennifer C

    2017-11-01

    Program directors (PDs) and trainees are often queried regarding the balance of service and education during pediatric residency training. We aimed to use qualitative methods to learn how pediatric residents and PDs define service and education and to identify activities that exemplify these concepts. Focus groups of pediatric residents and PDs were performed and the data qualitatively analyzed. Thematic analysis revealed 4 themes from focus group data: (1) misalignment of the perceived definition of service; (2) agreement about the definition of education; (3) overlapping perceptions of the value of service to training; and (4) additional suggestions for improved integration of education and service. Pediatric residents hold positive definitions of service and believe that service adds value to their education. Importantly, the discovery of heterogeneous definitions of service between pediatric residents and PDs warrants further investigation and may have ramifications for Accreditation Council for Graduate Medical Education and those responsible for residency curricula.

  17. Quantum computing. Defining and detecting quantum speedup.

    Science.gov (United States)

    Rønnow, Troels F; Wang, Zhihui; Job, Joshua; Boixo, Sergio; Isakov, Sergei V; Wecker, David; Martinis, John M; Lidar, Daniel A; Troyer, Matthias

    2014-07-25

    The development of small-scale quantum devices raises the question of how to fairly assess and detect quantum speedup. Here, we show how to define and measure quantum speedup and how to avoid pitfalls that might mask or fake such a speedup. We illustrate our discussion with data from tests run on a D-Wave Two device with up to 503 qubits. By using random spin glass instances as a benchmark, we found no evidence of quantum speedup when the entire data set is considered and obtained inconclusive results when comparing subsets of instances on an instance-by-instance basis. Our results do not rule out the possibility of speedup for other classes of problems and illustrate the subtle nature of the quantum speedup question. Copyright © 2014, American Association for the Advancement of Science.

  18. Software Defined Networking Demands on Software Technologies

    DEFF Research Database (Denmark)

    Galinac Grbac, T.; Caba, Cosmin Marius; Soler, José

    2015-01-01

    Software Defined Networking (SDN) is a networking approach based on a centralized control plane architecture with standardised interfaces between control and data planes. SDN enables fast configuration and reconfiguration of the network to enhance resource utilization and service performances....... This new approach enables a more dynamic and flexible network, which may adapt to user needs and application requirements. To this end, systemized solutions must be implemented in network software, aiming to provide secure network services that meet the required service performance levels. In this paper......, we review this new approach to networking from an architectural point of view, and identify and discuss some critical quality issues that require new developments in software technologies. These issues we discuss along with use case scenarios. Here in this paper we aim to identify challenges...

  19. Computing platforms for software-defined radio

    CERN Document Server

    Nurmi, Jari; Isoaho, Jouni; Garzia, Fabio

    2017-01-01

    This book addresses Software-Defined Radio (SDR) baseband processing from the computer architecture point of view, providing a detailed exploration of different computing platforms by classifying different approaches, highlighting the common features related to SDR requirements and by showing pros and cons of the proposed solutions. Coverage includes architectures exploiting parallelism by extending single-processor environment (such as VLIW, SIMD, TTA approaches), multi-core platforms distributing the computation to either a homogeneous array or a set of specialized heterogeneous processors, and architectures exploiting fine-grained, coarse-grained, or hybrid reconfigurability. Describes a computer engineering approach to SDR baseband processing hardware; Discusses implementation of numerous compute-intensive signal processing algorithms on single and multicore platforms; Enables deep understanding of optimization techniques related to power and energy consumption of multicore platforms using several basic a...

  20. Environmentally acceptable thread compounds: Requirements defined

    International Nuclear Information System (INIS)

    Stringfellow, W.D.; Hendriks, R.V.; Jacobs, N.L.

    1993-01-01

    New environmental regulations on thread compounds are now being enforced in several areas with strong maritime tradition and a sensitive environment. These areas include Indonesia, Alaska and portions of Norway. The industry generally recognizes the environmental concerns but, with wider enforcement of regulations imminent, has not been able to define clearly the requirements for environmental compliance. This paper, written in collaboration with The Netherlands State Supervision of Mines, is based on the National Policy on Thread Compounds of The Netherlands. This national policy is representative of policies being followed by other North Sea governments. Similar policies might well be adopted by other governments worldwide. These policies will affect the operator, drilling contractor, and supplier. This paper provides a specific and detailed definition of thread compound requirements by addressing four relevant categories. The categories of interest are regulatory approval, environmental, health, and performance

  1. 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

  2. Exposing the Myths, Defining the Future

    International Nuclear Information System (INIS)

    Slavov, S.

    2013-01-01

    With this official statement, the WEC calls for policymakers and industry leaders to ''get real'' as the World Energy Council as a global energy body exposes the myths by informing the energy debate and defines a path to a more sustainable energy future. The World Energy Council urged stakeholders to take urgent and incisive actions, to develop and transform the global energy system. Failure to do so could put aspirations on the triple challenge of WEC Energy Trilemma defined by affordability, accessibility and environmental sustainability at serious risk. Through its multi-year in-depth global studies and issue-mapping the WEC has found that challenges that energy sector is facing today are much more crucial than previously envisaged. The WEC's analysis has exposed a number of myths which influence our understanding of important aspects of the global energy landscape. If not challenged, these misconceptions will lead us down a path of complacency and missed opportunities. Much has, and still is, being done to secure energy future, but the WEC' s studies reveal that current pathways fall short of delivering on global aspirations of energy access, energy security and environmental improvements. If we are to derive the full economic and social benefits from energy resources, then we must take incisive and urgent action to modify our steps to energy solutions. The usual business approaches are not effective, the business as usual is not longer a solution. The focus has moved from large universal solutions to an appreciation of regional and national contexts and sharply differentiated consumer expectations.(author)

  3. Radiotherapy for brain metastases: defining palliative response

    International Nuclear Information System (INIS)

    Bezjak, Andrea; Adam, Janice; Panzarella, Tony; Levin, Wilfred; Barton, Rachael; Kirkbride, Peter; McLean, Michael; Mason, Warren; Wong, Chong Shun; Laperriere, Normand

    2001-01-01

    Background and purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. Materials and methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT

  4. Defining Future Directions for Endometriosis Research

    Science.gov (United States)

    D’Hooghe, Thomas M.; Fazleabas, Asgerally; Giudice, Linda C.; Montgomery, Grant W.; Petraglia, Felice; Taylor, Robert N.

    2013-01-01

    Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:23427182

  5. Enduring epigenetic landmarks define the cancer microenvironment

    Science.gov (United States)

    Pidsley, Ruth; Lawrence, Mitchell G.; Zotenko, Elena; Niranjan, Birunthi; Statham, Aaron; Song, Jenny; Chabanon, Roman M.; Qu, Wenjia; Wang, Hong; Richards, Michelle; Nair, Shalima S.; Armstrong, Nicola J.; Nim, Hieu T.; Papargiris, Melissa; Balanathan, Preetika; French, Hugh; Peters, Timothy; Norden, Sam; Ryan, Andrew; Pedersen, John; Kench, James; Daly, Roger J.; Horvath, Lisa G.; Stricker, Phillip; Frydenberg, Mark; Taylor, Renea A.; Stirzaker, Clare; Risbridger, Gail P.; Clark, Susan J.

    2018-01-01

    The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples. PMID:29650553

  6. Defining Ecosystem Assets for Natural Capital Accounting.

    Science.gov (United States)

    Hein, Lars; Bagstad, Ken; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems' capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks.

  7. Defining meridians: a modern basis of understanding.

    Science.gov (United States)

    Longhurst, John C

    2010-06-01

    Acupuncture, one of the primary methods of treatment in traditional Oriental medicine, is based on a system of meridians. Along the meridians lie acupuncture points or acupoints, which are stimulated by needling, pressure or heat to resolve a clinical problem. A number of methods have been used to identify meridians and to explain them anatomically. Thus, tendinomuscular structures, primo-vessels (Bonghan ducts), regions of increased temperature and low skin resistance have been suggested to represent meridians or as methods to identify them. However, none of these methods have met the criteria for a meridian, an entity that, when stimulated by acupuncture can result in clinical improvement. More recently, modern physiologists have put forward the "neural hypothesis" stating that the clinical influence of acupuncture is transmitted primarily through stimulation of sensory nerves that provide signals to the brain, which processes this information and then causes clinical changes associated with treatment. Although additional research is warranted to investigate the role of some of the structures identified, it seems clear that the peripheral and central nervous system can now be considered to be the most rational basis for defining meridians. The meridian maps and associated acupoints located along them are best viewed as road maps that can guide practitioners towards applying acupuncture to achieve optimal clinical results. Copyright 2010 Korean Pharmacopuncture Institute. Published by .. All rights reserved.

  8. Software Defined Networks in Wireless Sensor Architectures

    Directory of Open Access Journals (Sweden)

    Jesús Antonio Puente Fernández

    2018-03-01

    Full Text Available Nowadays, different protocols coexist in Internet that provides services to users. Unfortunately, control decisions and distributed management make it hard to control networks. These problems result in an inefficient and unpredictable network behaviour. Software Defined Networks (SDN is a new concept of network architecture. It intends to be more flexible and to simplify the management in networks with respect to traditional architectures. Each of these aspects are possible because of the separation of control plane (controller and data plane (switches in network devices. OpenFlow is the most common protocol for SDN networks that provides the communication between control and data planes. Moreover, the advantage of decoupling control and data planes enables a quick evolution of protocols and also its deployment without replacing data plane switches. In this survey, we review the SDN technology and the OpenFlow protocol and their related works. Specifically, we describe some technologies as Wireless Sensor Networks and Wireless Cellular Networks and how SDN can be included within them in order to solve their challenges. We classify different solutions for each technology attending to the problem that is being fixed.

  9. Defining the landscape of adaptive genetic diversity.

    Science.gov (United States)

    Eckert, Andrew J; Dyer, Rodney J

    2012-06-01

    Whether they are used to describe fitness, genome architecture or the spatial distribution of environmental variables, the concept of a landscape has figured prominently in our collective reasoning. The tradition of landscapes in evolutionary biology is one of fitness mapped onto axes defined by phenotypes or molecular sequence states. The characteristics of these landscapes depend on natural selection, which is structured across both genomic and environmental landscapes, and thus, the bridge among differing uses of the landscape concept (i.e. metaphorically or literally) is that of an adaptive phenotype and its distribution across geographical landscapes in relation to selective pressures. One of the ultimate goals of evolutionary biology should thus be to construct fitness landscapes in geographical space. Natural plant populations are ideal systems with which to explore the feasibility of attaining this goal, because much is known about the quantitative genetic architecture of complex traits for many different plant species. What is less known are the molecular components of this architecture. In this issue of Molecular Ecology, Parchman et al. (2012) pioneer one of the first truly genome-wide association studies in a tree that moves us closer to this form of mechanistic understanding for an adaptive phenotype in natural populations of lodgepole pine (Pinus contorta Dougl. ex Loud.). © 2012 Blackwell Publishing Ltd.

  10. Defining a standard metric for electricity savings

    International Nuclear Information System (INIS)

    Koomey, Jonathan; Akbari, Hashem; Blumstein, Carl; Brown, Marilyn; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B; Greenberg, Steve

    2010-01-01

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70% capacity factor with 7% T and D losses. Displacing such a plant for one year would save 3 billion kWh/year at the meter and reduce emissions by 3 million metric tons of CO 2 per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question-Dr Arthur H Rosenfeld.

  11. Defining a standard metric for electricity savings

    Energy Technology Data Exchange (ETDEWEB)

    Koomey, Jonathan [Lawrence Berkeley National Laboratory and Stanford University, PO Box 20313, Oakland, CA 94620-0313 (United States); Akbari, Hashem; Blumstein, Carl; Brown, Marilyn; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B; Greenberg, Steve, E-mail: JGKoomey@stanford.ed

    2010-01-15

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70% capacity factor with 7% T and D losses. Displacing such a plant for one year would save 3 billion kWh/year at the meter and reduce emissions by 3 million metric tons of CO{sub 2} per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question-Dr Arthur H Rosenfeld.

  12. Defining functional dyspepsia Definiendo la dispepsia funcional

    Directory of Open Access Journals (Sweden)

    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

  13. [Defining AIDS terminology. A practical approach].

    Science.gov (United States)

    Locutura, Jaime; Almirante, Benito; Berenguer, Juan; Muñoz, Agustín; Peña, José María

    2003-01-01

    Since the appearance of AIDS, the study of this disease has generated a large amount of information and an extensive related vocabulary comprised of new terms or terms borrowed from other scientific fields. The urgent need to provide names for newly described phenomena and concepts in this field has resulted in the application of terms that are not always appropriate from the linguistic and scientific points of view. We discuss the difficulties in attempting to create adequate AIDS terminology in the Spanish language, considering both the general problems involved in building any scientific vocabulary and the specific problems inherent to this activity in a field whose defining illness has important social connotations. The pressure exerted by the predominance of the English language in reporting scientific knowledge is considered, and the inappropriate words most often found in a review of current literature are examined. Finally, attending to the two most important criteria for the creation of new scientific terms, accuracy and linguistic correction, we propose some well thought-out alternatives that conform to the essence of the Spanish language.

  14. Defining Ecosystem Assets for Natural Capital Accounting

    Science.gov (United States)

    Hein, Lars; Bagstad, Ken; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems’ capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks. PMID:27828969

  15. Medical device software: defining key terms.

    Science.gov (United States)

    Pashkov, Vitalii; Gutorova, Nataliya; Harkusha, Andrii

    one of the areas of significant growth in medical devices has been the role of software - as an integral component of a medical device, as a standalone device and more recently as applications on mobile devices. The risk related to a malfunction of the standalone software used within healthcare is in itself not a criterion for its qualification or not as a medical device. It is therefore, necessary to clarify some criteria for the qualification of stand-alone software as medical devices Materials and methods: Ukrainian, European Union, United States of America legislation, Guidelines developed by European Commission and Food and Drug Administration's, recommendations represented by international voluntary group and scientific works. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. the legal regulation of software which is used for medical purpose in Ukraine limited to one definition. In European Union and United States of America were developed and applying special guidelines that help developers, manufactures and end users to difference software on types standing on medical purpose criteria. Software becomes more and more incorporated into medical devices. Developers and manufacturers may not have initially appreciated potential risks to patients and users such situation could have dangerous results for patients or users. It is necessary to develop and adopt the legislation that will intend to define the criteria for the qualification of medical device software and the application of the classification criteria to such software, provide some illustrative examples and step by step recommendations to qualify software as medical device.

  16. Software-defined Quantum Networking Ecosystem

    Energy Technology Data Exchange (ETDEWEB)

    2017-01-01

    The software enables a user to perform modeling and simulation of software-defined quantum networks. The software addresses the problem of how to synchronize transmission of quantum and classical signals through multi-node networks and to demonstrate quantum information protocols such as quantum teleportation. The software approaches this problem by generating a graphical model of the underlying network and attributing properties to each node and link in the graph. The graphical model is then simulated using a combination of discrete-event simulators to calculate the expected state of each node and link in the graph at a future time. A user interacts with the software by providing an initial network model and instantiating methods for the nodes to transmit information with each other. This includes writing application scripts in python that make use of the software library interfaces. A user then initiates the application scripts, which invokes the software simulation. The user then uses the built-in diagnostic tools to query the state of the simulation and to collect statistics on synchronization.

  17. Defining Astrology in Ancient and Classical History

    Science.gov (United States)

    Campion, Nicholas

    2015-05-01

    Astrology in the ancient and classical worlds can be partly defined by its role, and partly by the way in which scholars spoke about it. The problem is complicated by the fact that the word is Greek - it has no Babylonian or Egyptian cognates - and even in Greece it was interchangeable with its cousin, 'astronomy'. Yet if we are to understand the role of the sky, stars and planets in culture, debates about the nature of ancient astrology, by both classical and modern scholars, must be taken into account. This talk will consider modern scholars' typologies of ancient astrology, together with ancient debates from Cicero in the 1st century BC, to Plotinus (204/5-270 AD) and Isidore of Seville (c. 560 - 4 April 636). It will consider the implications for our understanding of astronomy's role in culture, and conclude that in the classical period astrology may be best understood through its diversity and allegiance to competing philosophies, and that its functions were therefore similarly varied.

  18. Defining ecosystem assets for natural capital accounting

    Science.gov (United States)

    Hein, Lars; Bagstad, Kenneth J.; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems’ capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks.

  19. Methodologies for defining quality of life

    Energy Technology Data Exchange (ETDEWEB)

    Glicken, J. [Ecological Planning and Toxicology, Inc., Albuquerque, NM (United States); Engi, D. [Sandia National Labs., Albuquerque, NM (United States)

    1996-10-10

    Quality of life as a concept has been used in many ways in the public policy arena. It can be used in summative evaluations to assess the impacts of policies or programs. Alternatively, it can be applied to formative evaluations to provide input to the formation of new policies. In short, it provides the context for the understanding needed to evaluate the results of choices that have been made in the public policy arena, or the potential of choices yet to be made. In either case, the public policy question revolves around the positive or negative impact the choice will have on quality of life, and the magnitude of that impact. This discussion will develop a conceptual framework that proposes that an assessment of quality of life is based on a comparison of expectations with experience. The framework defines four basic components from which these expectations arise: natural conditions, social conditions, the body, and the mind. Each one of these components is generally described, and associated with a general policy or rhetorical category which gives it its policy vocabulary--environmental quality, economic well-being, human health, and self-fulfillment.

  20. Defining a Standard Metric for Electricity Savings

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Marilyn; Akbari, Hashem; Blumstein, Carl; Koomey, Jonathan; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H.; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B.; Greenberg, Steve; Hafemeister, David; Harris, Jeff; Harvey, Hal; Heitz, Eric; Hirst, Eric; Hummel, Holmes; Kammen, Dan; Kelly, Henry; Laitner, Skip; Levine, Mark; Lovins, Amory; Masters, Gil; McMahon, James E.; Meier, Alan; Messenger, Michael; Millhone, John; Mills, Evan; Nadel, Steve; Nordman, Bruce; Price, Lynn; Romm, Joe; Ross, Marc; Rufo, Michael; Sathaye, Jayant; Schipper, Lee; Schneider, Stephen H; Sweeney, James L; Verdict, Malcolm; Vorsatz, Diana; Wang, Devra; Weinberg, Carl; Wilk, Richard; Wilson, John; Worrell, Ernst

    2009-03-01

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70percent capacity factor with 7percent T&D losses. Displacing such a plant for one year would save 3 billion kW h per year at the meter and reduce emissions by 3 million metric tons of CO2 per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question--Dr. Arthur H. Rosenfeld.

  1. G-NEST: A gene neighborhood scoring tool to identify co-conserved, co-expressed genes

    Science.gov (United States)

    In previous studies, gene neighborhoods--spatial clusters of co-expressed genes in the genome--have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Sc...

  2. HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

    DEFF Research Database (Denmark)

    Monforte, Antonella d'Arminio; Abrams, Donald; Pradier, Christian

    2008-01-01

    OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively......-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality...

  3. Novel gene sets improve set-level classification of prokaryotic gene expression data.

    Science.gov (United States)

    Holec, Matěj; Kuželka, Ondřej; Železný, Filip

    2015-10-28

    Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at http://ida.felk.cvut.cz/novelgenesets.tar.gz.

  4. Molecular signatures define two main classes of meningiomas

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2007-10-01

    Full Text Available Abstract Background Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis. Results We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups. Conclusion Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.

  5. Phylogenetic analysis to define feline immunodeficiency virus subtypes in 31 domestic cats in South Africa

    Directory of Open Access Journals (Sweden)

    R. Kann

    2006-06-01

    Full Text Available Feline immunodeficiency virus (FIV, a lentivirus, is an important pathogen of domestic cats around the world and has many similarities to human immunodeficiency virus (HIV. A characteristic of these lentiviruses is their extensive genetic diversity, which has been an obstacle in the development of successful vaccines. Of the FIV genes, the envelope gene is the most variable and sequence differences in a portion of this gene have been used to define 5 FIV subtypes (A, B, C, D and E. In this study, the proviral DNA sequence of the V3-V5 region of the envelope gene was determined in blood samples from 31 FIV positive cats from 4 different regions of South Africa. Phylogenetic analysis demonstrated the presence of both subtypes A and C, with subtype A predominating. These findings contribute to the understanding of the genetic diversity of FIV.

  6. Software Defined Common Processing System (SDCPS), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Coherent Logix, Incorporated proposes the Software Defined Common Processing System (SDCPS) program to facilitate the development of a Software Defined Radio...

  7. A Methodology to Define Flood Resilience

    Science.gov (United States)

    Tourbier, J.

    2012-04-01

    Flood resilience has become an internationally used term with an ever-increasing number of entries on the Internet. The SMARTeST Project is looking at approaches to flood resilience through case studies at cities in various countries, including Washington D.C. in the United States. In light of U.S. experiences a methodology is being proposed by the author that is intended to meet ecologic, spatial, structural, social, disaster relief and flood risk aspects. It concludes that: "Flood resilience combines (1) spatial, (2) structural, (3) social, and (4) risk management levels of flood preparedness." Flood resilience should incorporate all four levels, but not necessarily with equal emphasis. Stakeholders can assign priorities within different flood resilience levels and the considerations they contain, dividing 100% emphasis into four levels. This evaluation would be applied to planned and completed projects, considering existing conditions, goals and concepts. We have long known that the "road to market" for the implementation of flood resilience is linked to capacity building of stakeholders. It is a multidisciplinary enterprise, involving the integration of all the above aspects into the decision-making process. Traditional flood management has largely been influenced by what in the UK has been called "Silo Thinking", involving constituent organizations that are responsible for different elements, and are interested only in their defined part of the system. This barrier to innovation also has been called the "entrapment effect". Flood resilience is being defined as (1) SPATIAL FLOOD RESILIENCE implying the management of land by floodplain zoning, urban greening and management to reduce storm runoff through depression storage and by practicing Sustainable Urban Drainage (SUD's), Best Management Practices (BMP's, or Low Impact Development (LID). Ecologic processes and cultural elements are included. (2) STRUCTURAL FLOOD RESILIENCE referring to permanent flood defense

  8. Ramifications of defining high-level waste

    International Nuclear Information System (INIS)

    Wood, D.E.; Campbell, M.H.; Shupe, M.W.

    1987-01-01

    The Nuclear Regulatory Commission (NRC) is considering rule making to provide a concentration-based definition of high-level waste (HLW) under authority derived from the Nuclear Waste Policy Act (NWPA) of 1982 and the Low Level Waste Policy Amendments Act of 1985. The Department of Energy (DOE), which has the responsibility to dispose of certain kinds of commercial waste, is supporting development of a risk-based classification system by the Oak Ridge National Laboratory to assist in developing and implementing the NRC rule. The system is two dimensional, with the axes based on the phrases highly radioactive and requires permanent isolation in the definition of HLW in the NWPA. Defining HLW will reduce the ambiguity in the present source-based definition by providing concentration limits to establish which materials are to be called HLW. The system allows the possibility of greater-confinement disposal for some wastes which do not require the degree of isolation provided by a repository. The definition of HLW will provide a firm basis for waste processing options which involve partitioning of waste into a high-activity stream for repository disposal, and a low-activity stream for disposal elsewhere. Several possible classification systems have been derived and the characteristics of each are discussed. The Defense High Level Waste Technology Lead Office at DOE - Richland Operations Office, supported by Rockwell Hanford Operations, has coordinated reviews of the ORNL work by a technical peer review group and other DOE offices. The reviews produced several recommendations and identified several issues to be addressed in the NRC rule making. 10 references, 3 figures

  9. Defining malnutrition: A plea to rethink.

    Science.gov (United States)

    Soeters, P; Bozzetti, F; Cynober, L; Forbes, A; Shenkin, A; Sobotka, L

    2017-06-01

    In a recent consensus report in Clinical Nutrition the undernourished category of malnutrition was proposed to be defined and diagnosed on the basis of a low BMI or unintentional weight loss combined with low BMI or FFMI with certain cut off points. The definition was endorsed by ESPEN despite recent endorsement of a very different definition. The approach aims to assess whether nutritional intake is sufficient but is imprecise because a low BMI does not always indicate malnutrition and individuals with increasing BMI's may have decreasing FFM's. The pathophysiology of individuals, considered to be malnourished in rich countries and in areas with endemic malnutrition, results predominantly from deficient nutrition combined with infection/inflammation. Both elements jointly determine body composition and function and consequently outcome of disease, trauma or treatment. When following the consensus statement only an imprecise estimate is acquired of nutritional intake without knowing the impact of inflammation. Most importantly, functional abilities are not assessed. Consequently it will remain uncertain how well the individual can overcome stressful events, what the causes are of dysfunction, how to set priorities for treatment and how to predict the effect of nutritional support. We therefore advise to consider the pathophysiology of malnourished individuals leading to inclusion of the following elements in the definition of malnutrition: a disordered nutritional state resulting from a combination of inflammation and a negative nutrient balance, leading to changes in body composition, function and outcome. A precise diagnosis of malnutrition should be based on assessment of these elements. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  10. Defining the critical hurdles in cancer immunotherapy

    Science.gov (United States)

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  11. Towards defining restlessness in individuals with dementia.

    Science.gov (United States)

    Regier, Natalie G; Gitlin, Laura N

    2017-05-01

    Most individuals with dementia develop significant behavioral problems. Restlessness is a behavioral symptom frequently endorsed by caregivers as distressing, yet is variably defined and measured. Lack of conceptual and operational clarity hinders an understanding of this common behavioral type, its prevalence, and development of effective interventions. We advance a systematic definition and understanding of restlessness from which to enhance reporting and intervention development. We reviewed the literature for existing definitions and measures of restlessness, identified common elements across existing definitions, assessed fit with relevant theoretical frameworks, and explored the relationship between restlessness and other behavioral symptoms in a data set of 272 community-dwelling persons with dementia. Twenty-five scales assessing restlessness were identified. Shared components included motor/neurological, psychiatric, and needs-based features. Exploratory analyses suggest that restlessness may co-occur primarily with argumentation, anxiety, waking the caregiver, delusions/hallucinations, and wandering. We propose that restlessness consists of three key attributes: diffuse motor activity or motion subject to limited control, non-productive or disorganized behavior, and subjective distress. Restlessness should be differentiated from and not confused with wandering or elopement, pharmacological side effects, a (non-dementia) mental or movement disorder, or behaviors occurring in the context of a delirium or at end-of-life. Restlessness appears to denote a distinct set of behaviors that have overlapping but non-equivalent features with other behavioral symptoms. We propose that it reflects a complex behavior involving three key characteristics. Understanding its specific manifestations and which components are present can enhance tailoring interventions to specific contexts of this multicomponent behavioral type.

  12. Defining the critical hurdles in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Fox Bernard A

    2011-12-01

    Full Text Available Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC, convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  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. Future Scenarios for Software-Defined Metro and Access Networks and Software-Defined Photonics

    Directory of Open Access Journals (Sweden)

    Tommaso Muciaccia

    2017-01-01

    Full Text Available In recent years, architectures, devices, and components in telecommunication networks have been challenged by evolutionary and revolutionary factors which are drastically changing the traffic features. Most of these changes imply the need for major re-configurability and programmability not only in data-centers and core networks, but also in the metro-access segment. In a wide variety of contexts, this necessity has been addressed by the proposed introduction of the innovative paradigm of software-defined networks (SDNs. Several solutions inspired by the SDN model have been recently proposed also for metro and access networks, where the adoption of a new generation of software-defined reconfigurable integrated photonic devices is highly desirable. In this paper, we review the possible future application scenarios for software-defined metro and access networks and software-defined photonics (SDP, on the base of analytics, statistics, and surveys. This work describes the reasons underpinning the presented radical change of paradigm and summarizes the most significant solutions proposed in literature, with a specific emphasis to physical-layer reconfigurable networks and a focus on both architectures and devices.

  15. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  16. Defining Compensable Injury in Biomedical Research.

    Science.gov (United States)

    Larkin, Megan E

    2015-01-01

    Biomedical research provides a core social good by enabling medical progress. In the twenty-first century alone, this includes reducing transmission of HIV/AIDS, developing innovative therapies for cancer patients, and exploring the possibilities of personalized medicine. In order to continue to advance medical science, research relies on the voluntary participation of human subjects. Because research is inherently uncertain, unintended harm is an inevitable part of the research enterprise. Currently, injured research participants in the United States must turn to the “litigation lottery” of the tort system in search of compensation. This state of affairs fails research participants, who are too often left uncompensated for devastating losses, and makes the United States an outlier in the international community. In spite of forty years’ worth of Presidential Commissions and other respected voices calling for the development of a no-fault compensation system, no progress has been made to date. One of the reasons for this lack of progress is the failure to develop a coherent ethical basis for an obligation to provide compensation for research related injuries. This problem is exacerbated by the lack of a clear definition of “compensable injury” in the biomedical research context. This article makes a number of important contributions to the scholarship in this growing field. To begin, it examines compensation systems already in existence and concludes that there are four main definitional elements that must be used to define “compensable injury.” Next, it examines the justifications that have been put forth as the basis for an ethical obligation to provide compensation, and settles on retrospective nonmaleficence and distributive and compensatory justice as the most salient and persuasive. Finally, it uses the regulatory elements and the justifications discussed in the first two sections to develop a well-rounded definition of “compensable injury

  17. Understanding and defining bullying - adolescents' own views.

    Science.gov (United States)

    Hellström, Lisa; Persson, Louise; Hagquist, Curt

    2015-01-01

    The negative consequences of peer-victimization on children and adolescents are major public health concerns which have been subjected to extensive research. Given all efforts made to analyze and estimate the social and health consequences of peer-victimization, the adolescents' own experiences and understandings have had surprisingly little impact on the definition of bullying. Therefore, the aim of the current study is to explore adolescents' definitions of bullying. A questionnaire study (n = 128) and four focus group interviews (n = 21) were conducted among students aged 13 and 15. First, gender and age differences were analyzed with respect to what behaviors are considered bullying (questionnaire data). Second, analysis of what bullying is (focus group interviews) was conducted using qualitative content analysis. The adolescents own understanding and definition of bullying didn't just include the traditional criteria of repetition and power imbalance, but also a criterion based on the health consequences of bullying. The results showed that a single but hurtful or harmful incident also could be considered bullying irrespective of whether the traditional criteria were fulfilled or not. Further, girls and older students had a more inclusive view of bullying and reported more types of behaviors as bullying compared to boys and younger students. The results of the current study adds to the existing literature by showing that adolescents consider the victim's experience of hurt and harm as a criterion for defining bullying and not only as consequences of bullying. This may be of special relevance for the identification and classification of bullying incidents on the internet where devastating consequences have been reported from single incidents and the use of the traditional criteria of intent, repetition and power imbalance may not be as relevant as for traditional bullying. It implies that the traditional criteria included in most definitions of bullying

  18. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  19. Phylogenetic reconstruction of South American felids defined by protein electrophoresis.

    Science.gov (United States)

    Slattery, J P; Johnson, W E; Goldman, D; O'Brien, S J

    1994-09-01

    Phylogenetic associations among six closely related South American felid species were defined by changes in protein-encoding gene loci. We analyzed proteins isolated from skin fibroblasts using two-dimensional electrophoresis and allozymes extracted from blood cells. Genotypes were determined for multiple individuals of ocelot, margay, tigrina, Geoffroy's cat, kodkod, and pampas cat at 548 loci resolved by two-dimensional electrophoresis and 44 allozyme loci. Phenograms were constructed using the methods of Fitch-Margoliash and neighbor-joining on a matrix of Nei's unbiased genetic distances for all pairs of species. Results of a relative-rate test indicate changes in two-dimensional electrophoresis data are constant among all South American felids with respect to a hyena outgroup. Allelic frequencies were transformed to discrete character states for maximum parsimony analysis. Phylogenetic reconstruction indicates a major split occurred approximately 5-6 million years ago, leading to three groups within the ocelot lineage. The earliest divergence led to Leopardus tigrina, followed by a split between an ancestor of an unresolved trichotomy of three species (Oncifelis guigna, O. geoffroyi, and Lynchailuris colocolo) and a recent common ancestor of Leopardus pardalis and L. wiedii. The results suggest that modern South American felids are monophyletic and evolved rapidly after the formation of the Panama land bridge between North and South America.

  20. Defining the Thrombotic Risk in Patients with Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Fabrizio Vianello

    2011-01-01

    Full Text Available Polycythemia vera (PV and essential thrombocythemia (ET are two Philadelphia-negative myeloproliferative neoplasms (MPN associated with an acquired mutation in the JAK2 tyrosine kinase gene. There is a rare incidence of progression to myelofibrosis and myeloid metaplasia in both disorders, which may or may not precede transformation to acute myeloid leukemia, but thrombosis is the main cause of morbidity and mortality. The pathophysiology of thrombosis in patients with MPN is complex. Traditionally, abnormalities of platelet number and function have been claimed as the main players, but increased dynamic interactions between platelets, leukocytes, and the endothelium do probably represent a fundamental interplay in generating a thrombophilic state. In addition, endothelial dysfunction, a well-known risk factor for vascular disease, may play a role in the thrombotic risk of patients with PV and ET. The identification of plasma markers translating the hemostatic imbalance in patients with PV and ET would be extremely helpful in order to define the subgroup of patients with a significant clinical risk of thrombosis.

  1. Defining functional DNA elements in the human genome

    Science.gov (United States)

    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

  2. DEFINED CONTRIBUTION PLANS, DEFINED BENEFIT PLANS, AND THE ACCUMULATION OF RETIREMENT WEALTH

    Science.gov (United States)

    Poterba, James; Rauh, Joshua; Venti, Steven; Wise, David

    2010-01-01

    The private pension structure in the United States, once dominated by defined benefit (DB) plans, is currently divided between defined contribution (DC) and DB plans. Wealth accumulation in DC plans depends on the participant's contribution behavior and on financial market returns, while accumulation in DB plans is sensitive to a participant's labor market experience and to plan parameters. This paper simulates the distribution of retirement wealth under representative DB and DC plans. It uses data from the Health and Retirement Study (HRS) to explore how asset returns, earnings histories, and retirement plan characteristics contribute to the variation in retirement wealth outcomes. We simulate DC plan accumulation by randomly assigning individuals a share of wages that they and their employer contribute to the plan. We consider several possible asset allocation strategies, with asset returns drawn from the historical return distribution. Our DB plan simulations draw earnings histories from the HRS, and randomly assign each individual a pension plan drawn from a sample of large private and public defined benefit plans. The simulations yield distributions of both DC and DB wealth at retirement. Average retirement wealth accruals under current DC plans exceed average accruals under private sector DB plans, although DC plans are also more likely to generate very low retirement wealth outcomes. The comparison of current DC plans with more generous public sector DB plans is less definitive, because public sector DB plans are more generous on average than their private sector counterparts. PMID:21057597

  3. Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium.

    Science.gov (United States)

    Lindborg, Beth A; Brekke, John H; Vegoe, Amanda L; Ulrich, Connor B; Haider, Kerri T; Subramaniam, Sandhya; Venhuizen, Scott L; Eide, Cindy R; Orchard, Paul J; Chen, Weili; Wang, Qi; Pelaez, Francisco; Scott, Carolyn M; Kokkoli, Efrosini; Keirstead, Susan A; Dutton, James R; Tolar, Jakub; O'Brien, Timothy D

    2016-07-01

    Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10-14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. Tissue organoids are a promising technology with many potential applications, such as pharmaceutical screens and development of in vitro disease models, particularly for human polygenic conditions where animal models are insufficient. This work describes a robust and simple method for generating cerebral organoids from human induced pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. This method, by virtue of its simplicity and use of defined materials, greatly facilitates access to cerebral organoid technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. ©AlphaMed Press.

  4. Defining cell populations with single-cell gene expression profiling: correlations and identification of astrocyte subpopulations

    Czech Academy of Sciences Publication Activity Database

    Stahlberg, A.; Andersson, D.; Aurelius, J.; Faiz, M.; Pekna, M.; Kubista, Mikael; Pekny, M.

    2011-01-01

    Roč. 39, č. 4 (2011) ISSN 0305-1048 R&D Projects: GA AV ČR IAA500970904; GA ČR GAP303/10/1338 Institutional research plan: CEZ:AV0Z50520701 Keywords : EMBRYONIC STEM-CELLS * REAL-TIME PCR * MESSENGER-RNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.026, year: 2011

  5. A defined role for multiple Fanconi anemia gene products in DNA-damage-associated ubiquitination.

    Science.gov (United States)

    Tan, Winnie; Deans, Andrew J

    2017-06-01

    Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cell's genome stability by orchestrating the repair of interstrand cross-linking during the S phase of the cell cycle, preventing the chromosomal instability that is a key event in bone marrow failure syndrome. Central to the FA pathway is loss of monoubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins. Each protein, when mutated, can cause FA. The FA core-complex-catalyzed reaction is critical for signaling DNA cross-link damage such as that induced by chemotherapies. Here, we present a perspective on the current understanding of FANCI and FANCD2 monoubiquitination-mediated DNA repair. Our recent biochemical reconstitution of the monoubiquitination (and deubiquitination) reactions creates a paradigm for understanding FA. Further biochemical analysis will create new opportunities to address the leukemic phenotype of FA patients. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  6. Microarray Gene Expression Analysis of Murine Tumor Heterogeneity Defined by Dynamic Contrast-Enhanced MRI

    Directory of Open Access Journals (Sweden)

    Nick G. Costouros

    2002-07-01

    Full Text Available Current methods of studying angiogenesis are limited in their ability to serially evaluate in vivo function throughout a target tissue. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI and pharmacokinetic modeling provide a useful method for evaluating tissue vasculature based on contrast accumulation and washout. While it is often assumed that areas of high contrast enhancement and washout comprise areas of increased angiogenesis and tumor activity, the actual molecular pathways that are active in such areas are poorly understood. Using DCE-MRI in a murine subcutaneous tumor model, we were able to perform pharmacokinetic functional analysis of a tumor, coregistration of MRI images with histological cross-sections, immunohistochemistry, laser capture microdissection, and genetic profiling of tumor heterogeneity based on pharmacokinetic parameters. Using imaging as a template for biologic investigation, we have not found evidence of increased expression of proangiogenic modulators at the transcriptional level in either distinct pharmacokinetic region. Furthermore, these regions show no difference on histology and CD31 immunohistochemistry. However, the expression of ribosomal proteins was greatly increased in high enhancement and washout regions, implying increased protein translation and consequent increased cellular activity. Together, these findings point to the potential importance of posttranscriptional regulation in angiogenesis and the need for the development of angiogenesis-specific contrast agents to evaluate in vivo angiogenesis at a molecular level.

  7. Defined DNA-mediated assemblies of gene-expressing giant unilamellar vesicles

    DEFF Research Database (Denmark)

    Hadorn, M.; Boenzli, E.; Sørensen, Kristian T.

    2013-01-01

    The technological aspects of artificial vesicles as prominent cell mimics are evolving toward higher-order assemblies of functional vesicles with tissuelike architectures. Here, we demonstrate the spatially controlled DNA-directed bottom-up synthesis of complex microassemblies and macroassemblies...

  8. eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci

    DEFF Research Database (Denmark)

    Mousavi, Kambiz; Zare, Hossein; Dell'orso, Stefania

    2013-01-01

    )RNA acted to activate the downstream myogenic genes. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding Pol II assembly. By nuclease sensitivity assay, we found that eRNAs regulate genomic access of the transcriptional...... complex to defined regulatory regions. In conclusion, our data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events....

  9. Ageing genes

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2018-01-01

    The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan...... of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000...... virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance...

  10. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

    Science.gov (United States)

    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  11. Defining the Core Genome of Salmonella enterica Serovar Typhimurium for Genomic Surveillance and Epidemiological Typing

    Science.gov (United States)

    Fu, Songzhe; Octavia, Sophie; Tanaka, Mark M.; Sintchenko, Vitali

    2015-01-01

    Salmonella enterica serovar Typhimurium is the most common Salmonella serovar causing foodborne infections in Australia and many other countries. Twenty-one S. Typhimurium strains from Salmonella reference collection A (SARA) were analyzed using Illumina high-throughput genome sequencing. Single nucleotide polymorphisms (SNPs) in 21 SARA strains ranged from 46 to 11,916 SNPs, with an average of 1,577 SNPs per strain. Together with 47 strains selected from publicly available S. Typhimurium genomes, the S. Typhimurium core genes (STCG) were determined. The STCG consist of 3,846 genes, a set that is much larger than that of the 2,882 Salmonella core genes (SCG) found previously. The STCG together with 1,576 core intergenic regions (IGRs) were defined as the S. Typhimurium core genome. Using 93 S. Typhimurium genomes from 13 epidemiologically confirmed community outbreaks, we demonstrated that typing based on the S. Typhimurium core genome (STCG plus core IGRs) provides superior resolution and higher discriminatory power than that based on SCG for outbreak investigation and molecular epidemiology of S. Typhimurium. STCG and STCG plus core IGR typing achieved 100% separation of all outbreaks compared to that of SCG typing, which failed to separate isolates from two outbreaks from background isolates. Defining the S. Typhimurium core genome allows standardization of genes/regions to be used for high-resolution epidemiological typing and genomic surveillance of S. Typhimurium. PMID:26019201

  12. Regional neural tube closure defined by the Grainy head-like transcription factors.

    Science.gov (United States)

    Rifat, Yeliz; Parekh, Vishwas; Wilanowski, Tomasz; Hislop, Nikki R; Auden, Alana; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

    2010-09-15

    Primary neurulation in mammals has been defined by distinct anatomical closure sites, at the hindbrain/cervical spine (closure 1), forebrain/midbrain boundary (closure 2), and rostral end of the forebrain (closure 3). Zones of neurulation have also been characterized by morphologic differences in neural fold elevation, with non-neural ectoderm-induced formation of paired dorso-lateral hinge points (DLHP) essential for neural tube closure in the cranial and lower spinal cord regions, and notochord-induced bending at the median hinge point (MHP) sufficient for closure in the upper spinal region. Here we identify a unifying molecular basis for these observations based on the function of the non-neural ectoderm-specific Grainy head-like genes in mice. Using a gene-targeting approach we show that deletion of Grhl2 results in failed closure 3, with mutants exhibiting a split-face malformation and exencephaly, associated with failure of neuro-epithelial folding at the DLHP. Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation. The two genes contribute equally to closure 2, where only Grhl gene dosage is limiting. Combined deletion of Grhl2 and Grhl3 induces severe rostral and caudal neural tube defects, but DLHP-independent closure 1 proceeds normally in the upper spinal region. These findings provide a molecular basis for non-neural ectoderm mediated formation of the DLHP that is critical for complete neuraxis closure. (c) 2010 Elsevier Inc. All rights reserved.

  13. The duplicated genes database: identification and functional annotation of co-localised duplicated genes across genomes.

    Directory of Open Access Journals (Sweden)

    Marion Ouedraogo

    Full Text Available BACKGROUND: There has been a surge in studies linking genome structure and gene expression, with special focus on duplicated genes. Although initially duplicated from the same sequence, duplicated genes can diverge strongly over evolution and take on different functions or regulated expression. However, information on the function and expression of duplicated genes remains sparse. Identifying groups of duplicated genes in different genomes and characterizing their expression and function would therefore be of great interest to the research community. The 'Duplicated Genes Database' (DGD was developed for this purpose. METHODOLOGY: Nine species were included in the DGD. For each species, BLAST analyses were conducted on peptide sequences corresponding to the genes mapped on a same chromosome. Groups of duplicated genes were defined based on these pairwise BLAST comparisons and the genomic location of the genes. For each group, Pearson correlations between gene expression data and semantic similarities between functional GO annotations were also computed when the relevant information was available. CONCLUSIONS: The Duplicated Gene Database provides a list of co-localised and duplicated genes for several species with the available gene co-expression level and semantic similarity value of functional annotation. Adding these data to the groups of duplicated genes provides biological information that can prove useful to gene expression analyses. The Duplicated Gene Database can be freely accessed through the DGD website at http://dgd.genouest.org.

  14. Utilising artificial intelligence in software defined wireless sensor network

    CSIR Research Space (South Africa)

    Matlou, OG

    2017-10-01

    Full Text Available Software Defined Wireless Sensor Network (SDWSN) is realised by infusing Software Defined Network (SDN) model in Wireless Sensor Network (WSN), Reason for that is to overcome the challenges of WSN. Artificial Intelligence (AI) and machine learning...

  15. [Gene doping: gene transfer and possible molecular detection].

    Science.gov (United States)

    Argüelles, Carlos Francisco; Hernández-Zamora, Edgar

    2007-01-01

    The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

  16. Gene coexpression network analysis as a source of functional annotation for rice genes.

    Directory of Open Access Journals (Sweden)

    Kevin L Childs

    Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional

  17. 48 CFR 311.7000 - Defining electronic information technology requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Defining electronic information technology requirements. 311.7000 Section 311.7000 Federal Acquisition Regulations System HEALTH... Accessibility Standards 311.7000 Defining electronic information technology requirements. HHS staff that define...

  18. Variable Bandwidth Analog Channel Filters for Software Defined Radio

    NARCIS (Netherlands)

    Arkesteijn, V.J.; Klumperink, Eric A.M.; Nauta, Bram

    2001-01-01

    An important aspect of Software Defined Radio is the ability to define the bandwidth of the filter that selects the desired channel. This paper first explains the importance of channel filtering. Then the advantage of analog channel filtering with a variable bandwidth in a Software Defined Radio is

  19. Defining Generic Architecture for Cloud Infrastructure as a Service model

    NARCIS (Netherlands)

    Demchenko, Y.; de Laat, C.

    2011-01-01

    Infrastructure as a Service (IaaS) is one of the provisioning models for Clouds as defined in the NIST Clouds definition. Although widely used, current IaaS implementations and solutions doesn’t have common and well defined architecture model. The paper attempts to define a generic architecture for

  20. Defining generic architecture for Cloud IaaS provisioning model

    NARCIS (Netherlands)

    Demchenko, Y.; de Laat, C.; Mavrin, A.; Leymann, F.; Ivanov, I.; van Sinderen, M.; Shishkov, B.

    2011-01-01

    Infrastructure as a Service (IaaS) is one of the provisioning models for Clouds as defined in the NIST Clouds definition. Although widely used, current IaaS implementations and solutions doesn’t have common and well defined architecture model. The paper attempts to define a generic architecture for

  1. Gene doping.

    Science.gov (United States)

    Haisma, H J; de Hon, O

    2006-04-01

    Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping.

  2. A model to compare a defined benefit pension fund with a defined contribution provident fund

    Directory of Open Access Journals (Sweden)

    J.M. Nevin

    2003-12-01

    Full Text Available During 1994 universities and certain other institutions were given the option of setting up private retirement funds as an alternative to the AIPF. Because of the underfundedness of the AIPF only a substantially reduced Actuarial Reserve Value could be transferred to the new fund on behalf of each member. Employees at these institutions had to make the difficult decision of whether to remain a member of the AIPF or to join a new fund. Several institutions created defined contribution funds as an alternative to the AIPF. In such funds the member carries the investment risk and most institutions felt the need to provide some form of top-up of the Transfer Value. A simple mathematical model is formulated to aid in the comparison of expected retirement benefits under the AIPF and a private fund and to investigate the management problem of distributing additional top-up funds in a fair manner amongst the various age groups within the fund.

  3. Statistical Redundancy Testing for Improved Gene Selection in Cancer Classification Using Microarray Data

    Directory of Open Access Journals (Sweden)

    J. Sunil Rao

    2007-01-01

    Full Text Available In gene selection for cancer classifi cation using microarray data, we define an eigenvalue-ratio statistic to measure a gene’s contribution to the joint discriminability when this gene is included into a set of genes. Based on this eigenvalueratio statistic, we define a novel hypothesis testing for gene statistical redundancy and propose two gene selection methods. Simulation studies illustrate the agreement between statistical redundancy testing and gene selection methods. Real data examples show the proposed gene selection methods can select a compact gene subset which can not only be used to build high quality cancer classifiers but also show biological relevance.

  4. Gene Locater

    DEFF Research Database (Denmark)

    Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur

    2012-01-01

    software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...... of flexibility in calculating genetic linkage and displaying linkage group. Among other features, this software enables user to identify linkage groups with output visualized graphically. The program calculates interference and coefficient of coincidence with elevated accuracy in sample datasets. AVAILABILITY...

  5. Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

    Directory of Open Access Journals (Sweden)

    Tintle Nathan L

    2012-08-01

    Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.

  6. Graphs for information security control in software defined networks

    Science.gov (United States)

    Grusho, Alexander A.; Abaev, Pavel O.; Shorgin, Sergey Ya.; Timonina, Elena E.

    2017-07-01

    Information security control in software defined networks (SDN) is connected with execution of the security policy rules regulating information accesses and protection against distribution of the malicious code and harmful influences. The paper offers a representation of a security policy in the form of hierarchical structure which in case of distribution of resources for the solution of tasks defines graphs of admissible interactions in a networks. These graphs define commutation tables of switches via the SDN controller.

  7. 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...

  8. Non-self-adjoint Hamiltonians defined by generalized Riesz bases

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, H., E-mail: h-inoue@math.kyushu-u.ac.jp [Graduate School of Mathematics, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 (Japan); Takakura, M., E-mail: mayumi@fukuoka-u.ac.jp [Department of Applied Mathematics, Fukuoka University, Fukuoka 814-0180 (Japan)

    2016-08-15

    Bagarello, Inoue, and Trapani [J. Math. Phys. 55, 033501 (2014)] investigated some operators defined by the Riesz bases. These operators connect with quasi-Hermitian quantum mechanics, and its relatives. In this paper, we introduce a notion of generalized Riesz bases which is a generalization of Riesz bases and investigate some operators defined by the generalized Riesz bases by changing the frameworks of the operators defined in the work of Bagarello, Inoue, and Trapani.

  9. The mother centriole plays an instructive role in defining cell geometry.

    Directory of Open Access Journals (Sweden)

    Jessica L Feldman

    2007-06-01

    Full Text Available Centriole positioning is a key step in establishment and propagation of cell geometry, but the mechanism of this positioning is unknown. The ability of pre-existing centrioles to induce formation of new centrioles at a defined angle relative to themselves suggests they may have the capacity to transmit spatial information to their daughters. Using three-dimensional computer-aided analysis of cell morphology in Chlamydomonas, we identify six genes required for centriole positioning relative to overall cell polarity, four of which have known sequences. We show that the distal portion of the centriole is critical for positioning, and that the centriole positions the nucleus rather than vice versa. We obtain evidence that the daughter centriole is unable to respond to normal positioning cues and relies on the mother for positional information. Our results represent a clear example of "cytotaxis" as defined by Sonneborn, and suggest that centrioles can play a key function in propagation of cellular geometry from one generation to the next. The genes documented here that are required for proper centriole positioning may represent a new class of ciliary disease genes, defects in which would be expected to cause disorganized ciliary position and impaired function.

  10. A molecularly defined duplication set for the X chromosome of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Venken, Koen J. T.; Popodi, Ellen; Holtzman, Stacy L.; Schulze, Karen L.; Park, Soo; Carlson, Joseph W.; Hoskins, Roger A.; Bellen, Hugo J.; Kaufman, Thomas C.

    2010-07-22

    We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using C31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

  11. A molecularly defined duplication set for the X chromosome of Drosophila melanogaster.

    Science.gov (United States)

    Venken, Koen J T; Popodi, Ellen; Holtzman, Stacy L; Schulze, Karen L; Park, Soo; Carlson, Joseph W; Hoskins, Roger A; Bellen, Hugo J; Kaufman, Thomas C

    2010-12-01

    We describe a molecularly defined duplication kit for the X chromosome of Drosophila melanogaster. A set of 408 overlapping P[acman] BAC clones was used to create small duplications (average length 88 kb) covering the 22-Mb sequenced portion of the chromosome. The BAC clones were inserted into an attP docking site on chromosome 3L using ΦC31 integrase, allowing direct comparison of different transgenes. The insertions complement 92% of the essential and viable mutations and deletions tested, demonstrating that almost all Drosophila genes are compact and that the current annotations of the genome are reasonably accurate. Moreover, almost all genes are tolerated at twice the normal dosage. Finally, we more precisely mapped two regions at which duplications cause diplo-lethality in males. This collection comprises the first molecularly defined duplication set to cover a whole chromosome in a multicellular organism. The work presented removes a long-standing barrier to genetic analysis of the Drosophila X chromosome, will greatly facilitate functional assays of X-linked genes in vivo, and provides a model for functional analyses of entire chromosomes in other species.

  12. Factors stimulating riboflavin produced by Lactobacillus plantarum CRL 725 grown in a semi-defined medium.

    Science.gov (United States)

    Juarez Del Valle, Marianela; Laiño, Jonathan Emiliano; Savoy de Giori, Graciela; LeBlanc, Jean Guy

    2017-03-01

    Riboflavin (vitamin B 2 ) is one of the B-group water-soluble vitamins and is essential for energy metabolism of the cell. The aim of this study was to determine factors that affect riboflavin production by Lactobacillus (L.) plantarum CRL 725 grown in a semi defined medium and evaluate the expression of its rib genes. The factors found to enhance riboflavin production in this medium were incubation at 30 °C, and the addition of specific medium constituents, such as casamino acids (10 g L -1 ), guanosine (0.04 g L -1 ), and sucrose as carbon source (20 g L -1 ). In these conditions, higher riboflavin concentrations were directly associated with significant increases in the expression of ribA, ribB, and ribC genes. The culture conditions defined in this work and its application to a roseoflavin resistant mutant of L. plantarum allowed for a sixfold increase in riboflavin concentrations in our semi-defined medium which were also significantly higher than those obtained previously using the same strain to ferment soymilk. These conditions should thus be evaluated to increase vitamin production in fermented foods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Software Defined Common Processing System (SDCPS), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Coherent Logix, Incorporated (CLX) proposes the development of a Software Defined Common Processing System (SDCPS) that leverages the inherent advantages of an...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Differential DNA methylation patterns define status epilepticus and epileptic tolerance.

    Science.gov (United States)

    Miller-Delaney, Suzanne F C; Das, Sudipto; Sano, Takanori; Jimenez-Mateos, Eva M; Bryan, Kenneth; Buckley, Patrick G; Stallings, Raymond L; Henshall, David C

    2012-02-01

    Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with >90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus.

  16. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu

    2012-01-01

    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  17. The Caenorhabditis chemoreceptor gene families

    OpenAIRE

    Robertson Hugh M; Thomas James H

    2008-01-01

    Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-...

  18. Unlocking the treasure trove: from genes to schizophrenia biology.

    Science.gov (United States)

    McCarthy, Shane E; McCombie, W Richard; Corvin, Aiden

    2014-05-01

    Significant progress is being made in defining the genetic etiology of schizophrenia. As the list of implicated genes grows, parallel developments in gene editing technology provide new methods to investigate gene function in model systems. The confluence of these two research fields--gene discovery and functional biology--may offer novel insights into schizophrenia etiology. We review recent advances in these fields, consider the likely obstacles to progress, and consider strategies as to how these can be overcome.

  19. Developing social standards for wilderness encounters in Mount Rainier National Park: Manager-defined versus visitor-defined standards

    Science.gov (United States)

    Kristopher J. Lah

    2000-01-01

    This research compared the differences found between manager-defined and visitor-defined social standards for wilderness encounters in Mount Rainier National Park. Social standards in recreation areas of public land are defined by what is acceptable to the public, in addition to the area’s management. Social standards for the encounter indicator in Mount Rainier’s...

  20. 75 FR 27927 - Diversification Requirements for Certain Defined Contribution Plans

    Science.gov (United States)

    2010-05-19

    ... section 414(l) with respect to any other defined benefit plan or defined contribution plan maintained by... disclosure of the fund's portfolio holdings (for example, Form N-CSR, ``Certified Shareholder Report of... securities, as well as a direct or indirect benefit that is conditioned on investment in employer securities...

  1. 47 CFR 2.801 - Radiofrequency device defined.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Radiofrequency device defined. 2.801 Section 2... MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.801 Radiofrequency device defined. As used in this part, a radiofrequency device is any device which in its operation is capable of...

  2. 33 CFR 211.1 - Real estate defined.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Real estate defined. 211.1... DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.1 Real estate defined. The term real estate as used in this part includes land...

  3. 46 CFR 9.5 - Night, Sunday, and holiday defined.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Night, Sunday, and holiday defined. 9.5 Section 9.5... COMPENSATION FOR OVERTIME SERVICES § 9.5 Night, Sunday, and holiday defined. (a) For the purpose of this part... term holiday shall mean only national legal public holidays, viz., January 1, February 22, May 30, July...

  4. 12 CFR 914.1 - Regulatory Report defined.

    Science.gov (United States)

    2010-01-01

    ... Bank. (b) Examples. Regulatory Report includes: (1) Call reports and reports of instrument-level risk... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Regulatory Report defined. 914.1 Section 914.1... DATA AVAILABILITY AND REPORTING § 914.1 Regulatory Report defined. (a) Definition. Regulatory Report...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Defined Contribution Pension Plans: Mutual Fund Asset Allocation Changes

    OpenAIRE

    Clemens Sialm; Laura Starks; Hanjiang Zhang

    2015-01-01

    In this paper we compare changes in asset allocations between mutual funds held in defined contribution pension plans and funds held by other investors. We investigate how flows into equity and fixed income mutual funds depend on macroeconomic conditions. We find that defined contribution plans react more sensitively to these conditions, suggesting effects on mutual fund managers and other investors.

  8. Defining nuclear medical file formal based on DICOM standard

    International Nuclear Information System (INIS)

    He Bin; Jin Yongjie; Li Yulan

    2001-01-01

    With the wide application of computer technology in medical area, DICOM is becoming the standard of digital imaging and communication. The author discusses how to define medical imaging file formal based on DICOM standard. It also introduces the format of ANMIS system the authors defined the validity and integrality of this format

  9. 16 CFR 238.0 - Bait advertising defined. 1

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring but...

  10. 26 CFR 1.1250-2 - Additional depreciation defined.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Additional depreciation defined. 1.1250-2... Additional depreciation defined. (a) In general—(1) Definition for purposes of section 1250(b)(1). Except as... depreciation means: (i) In the case of property which at the time of disposition has a holding period under...

  11. Forward and backward dynamics in implicitly defined overlapping generations models

    NARCIS (Netherlands)

    Gardini, L.; Hommes, C.; Tramontana, F.; de Vilder, R.

    2009-01-01

    In dynamic economic models derived from optimization principles, the forward equilibrium dynamics may not be uniquely defined, while the backward dynamics is well defined. We derive properties of the global forward equilibrium paths based on properties of the backward dynamics. We propose the

  12. User constraints for reliable user-defined smart home scenarios

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Nielsen, Michael Kvist; Pedersen, Thomas

    2016-01-01

    Defining control scenarios in a smart home is a difficult task for end users. In particular, one concern is that user-defined scenarios could lead to unsafe or undesired state of the system. To help them explore scenario specifications, we propose in this paper a system that enables specification...

  13. Defining and Assessing Team Skills of Business and Accountancy Students

    Science.gov (United States)

    Alghalith, Nabil; Blum, Michael; Medlock, Amanda; Weber, Sandy

    2004-01-01

    The objectives of the project are (1) to define the skills necessary for students to work effectively with others to achieve common goals, and (2) to develop an assessment instrument to measure student progress toward achieving these skills. The defined skill set will form a basis for common expectations related to team skills that will be shared…

  14. Defining Sustainable Universities Following Public Opinion Formation Process

    Science.gov (United States)

    Zaptcioglu Celikdemir, Deniz; Gunay, Gonca; Katrinli, Alev; Penbek Alpbaz, Sebnem

    2017-01-01

    Purpose: The purpose of this paper is to define the sustainable university in Turkey, by considering perspectives of various stakeholders such as experts, intellectual, public, political parties and media using public opinion formation analysis. The paper aims to re-define the "sustainable university" with all dimensions including…

  15. 26 CFR 1.761-1 - Terms defined.

    Science.gov (United States)

    2010-04-01

    ... TAXES Definitions § 1.761-1 Terms defined. (a) Partnership. The term partnership means a partnership as... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Terms defined. 1.761-1 Section 1.761-1 Internal... means a member of a partnership. (c) Partnership agreement. For the purposes of subchapter K, a...

  16. Gene doping: gene delivery for olympic victory

    OpenAIRE

    Gould, David

    2012-01-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...

  17. 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

  18. 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.

  19. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

    International Nuclear Information System (INIS)

    Nicolay, Nils H.; Sommer, Eva; Lopez, Ramon; Wirkner, Ute; Trinh, Thuy; Sisombath, Sonevisay; Debus, Jürgen; Ho, Anthony D.; Saffrich, Rainer; Huber, Peter E.

    2013-01-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression

  20. 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.

  1. Genes and Hearing Loss

    Science.gov (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  2. Network Diffusion-Based Prioritization of Autism Risk Genes Identifies Significantly Connected Gene Modules

    Directory of Open Access Journals (Sweden)

    Ettore Mosca

    2017-09-01

    Full Text Available Autism spectrum disorder (ASD is marked by a strong genetic heterogeneity, which is underlined by the low overlap between ASD risk gene lists proposed in different studies. In this context, molecular networks can be used to analyze the results of several genome-wide studies in order to underline those network regions harboring genetic variations associated with ASD, the so-called “disease modules.” In this work, we used a recent network diffusion-based approach to jointly analyze multiple ASD risk gene lists. We defined genome-scale prioritizations of human genes in relation to ASD genes from multiple studies, found significantly connected gene modules associated with ASD and predicted genes functionally related to ASD risk genes. Most of them play a role in synapsis and neuronal development and function; many are related to syndromes that can be in comorbidity with ASD and the remaining are involved in epigenetics, cell cycle, cell adhesion and cancer.

  3. Service-oriented Software Defined Optical Networks for Cloud Computing

    Science.gov (United States)

    Liu, Yuze; Li, Hui; Ji, Yuefeng

    2017-10-01

    With the development of big data and cloud computing technology, the traditional software-defined network is facing new challenges (e.g., ubiquitous accessibility, higher bandwidth, more flexible management and greater security). This paper proposes a new service-oriented software defined optical network architecture, including a resource layer, a service abstract layer, a control layer and an application layer. We then dwell on the corresponding service providing method. Different service ID is used to identify the service a device can offer. Finally, we experimentally evaluate that proposed service providing method can be applied to transmit different services based on the service ID in the service-oriented software defined optical network.

  4. Evolutionary signatures amongst disease genes permit novel methods for gene prioritization and construction of informative gene-based networks.

    Directory of Open Access Journals (Sweden)

    Nolan Priedigkeit

    2015-02-01

    Full Text Available Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC, is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting "disease map" network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks.

  5. Gene composer: database software for protein construct design, codon engineering, and gene synthesis.

    Science.gov (United States)

    Lorimer, Don; Raymond, Amy; Walchli, John; Mixon, Mark; Barrow, Adrienne; Wallace, Ellen; Grice, Rena; Burgin, Alex; Stewart, Lance

    2009-04-21

    To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene assembly procedure with mis-match specific endonuclease

  6. Gene Composer: database software for protein construct design, codon engineering, and gene synthesis

    Directory of Open Access Journals (Sweden)

    Mixon Mark

    2009-04-01

    Full Text Available Abstract Background To improve efficiency in high throughput protein structure determination, we have developed a database software package, Gene Composer, which facilitates the information-rich design of protein constructs and their codon engineered synthetic gene sequences. With its modular workflow design and numerous graphical user interfaces, Gene Composer enables researchers to perform all common bio-informatics steps used in modern structure guided protein engineering and synthetic gene engineering. Results An interactive Alignment Viewer allows the researcher to simultaneously visualize sequence conservation in the context of known protein secondary structure, ligand contacts, water contacts, crystal contacts, B-factors, solvent accessible area, residue property type and several other useful property views. The Construct Design Module enables the facile design of novel protein constructs with altered N- and C-termini, internal insertions or deletions, point mutations, and desired affinity tags. The modifications can be combined and permuted into multiple protein constructs, and then virtually cloned in silico into defined expression vectors. The Gene Design Module uses a protein-to-gene algorithm that automates the back-translation of a protein amino acid sequence into a codon engineered nucleic acid gene sequence according to a selected codon usage table with minimal codon usage threshold, defined G:C% content, and desired sequence features achieved through synonymous codon selection that is optimized for the intended expression system. The gene-to-oligo algorithm of the Gene Design Module plans out all of the required overlapping oligonucleotides and mutagenic primers needed to synthesize the desired gene constructs by PCR, and for physically cloning them into selected vectors by the most popular subcloning strategies. Conclusion We present a complete description of Gene Composer functionality, and an efficient PCR-based synthetic gene

  7. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

  8. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers

    Directory of Open Access Journals (Sweden)

    Ali Jabbari

    2016-05-01

    Full Text Available Alopecia areata (AA is an autoimmune disease typified by nonscarring hair loss with a variable clinical course. In this study, we conducted whole genome gene expression analysis of 96 human scalp skin biopsy specimens from AA or normal control subjects. Based on gene expression profiling, samples formed distinct clusters based on the presence or absence of disease as well as disease phenotype (patchy disease compared with alopecia totalis or universalis. Differential gene expression analysis allowed us to robustly demonstrate graded immune activity in samples of increasing phenotypic severity and generate a quantitative gene expression scoring system that classified samples based on interferon and cytotoxic T lymphocyte immune signatures critical for disease pathogenesis.

  9. Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

    Science.gov (United States)

    Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

    2017-08-01

    This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  10. Defining a Cancer Dependency Map | Office of Cancer Genomics

    Science.gov (United States)

    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.

  11. Software Defined Radio Datalink Implementation Using PC-Type Computers

    National Research Council Canada - National Science Library

    Zafeiropoulos, Georgios

    2003-01-01

    The objective of this thesis was to examine the feasibility of implementation and the performance of a Software Defined Radio datalink, using a common PC type host computer and a high level programming language...

  12. 29 CFR 779.247 - “Goods” defined.

    Science.gov (United States)

    2010-07-01

    ... OR SERVICES Employment to Which the Act May Apply; Enterprise Coverage Interstate Inflow Test Under... Act is defined in section 3(i) of the Act. The statutory definition is quoted in § 779.14, and is...

  13. Defining Criteria for Handover to Civilian Officials in Relief Operations

    National Research Council Canada - National Science Library

    Bessler, John

    2008-01-01

    .... Department of Defense Directive (DoDD) 3000.05 directs that the military shall be prepared to accomplish 'all tasks necessary to establish or maintain order when civilians are unable to do so,' but the metrics which define success...

  14. Professional excellence : defining learning outcomes for honours higher education

    NARCIS (Netherlands)

    Fuller, Melissa; Robbe, Patricia; Wolfensberger, Marca

    2016-01-01

    Purpose Honours programs prepare talented students to become future excellent professionals . However, competences defining an excellent professional have not been elucidated yet. We investigated how professionals characterize an excellent communication professional, aiming to develop a competence

  15. User defined function for transformation of ellipsoidal coordinates

    Directory of Open Access Journals (Sweden)

    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.

  16. Multi-channel software defined radio experimental evaluation and analysis

    CSIR Research Space (South Africa)

    Van der Merwe, JR

    2014-09-01

    Full Text Available Multi-channel software-defined radios (SDRs) can be utilised as inexpensive prototyping platforms for transceiver arrays. The application for multi-channel prototyping is discussed and measured results of coherent channels for both receiver...

  17. Radiation Tolerant Software Defined Video Processor, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — MaXentric's is proposing a radiation tolerant Software Define Video Processor, codenamed SDVP, for the problem of advanced motion imaging in the space environment....

  18. Software defined radios from smart(er) to cognitive

    CERN Document Server

    Pollin, Sofie; Van der Perre, Liesbet

    2011-01-01

    Software Defined Radios presents a systematic approach to dealing with the complexity of wireless systems with varying standards. The text aims to enable smart operation of radios with impressive efficiency gains, without hampering the quality of service.

  19. Multiplexed Dosing Assays by Digitally Definable Hydrogel Volumes

    DEFF Research Database (Denmark)

    Faralli, Adele; Melander, Fredrik; Larsen, Esben Kjær Unmack

    2016-01-01

    Stable and low-cost multiplexed drug sensitivity assays using small volumes of cells or tissue are in demand for personalized medicine, including patientspecific combination chemotherapy. Spatially defined projected light photopolymerization of hydrogels with embedded active compounds is introduc...

  20. Defining Driver DNA Methylation Changes in Human Cancer

    Directory of Open Access Journals (Sweden)

    Gerd P. Pfeifer

    2018-04-01

    Full Text Available Human malignant tumors are characterized by pervasive changes in the patterns of DNA methylation. These changes include a globally hypomethylated tumor cell genome and the focal hypermethylation of numerous 5′-cytosine-phosphate-guanine-3′ (CpG islands, many of them associated with gene promoters. It has been challenging to link specific DNA methylation changes with tumorigenesis in a cause-and-effect relationship. Some evidence suggests that cancer-associated DNA hypomethylation may increase genomic instability. Promoter hypermethylation events can lead to silencing of genes functioning in pathways reflecting hallmarks of cancer, including DNA repair, cell cycle regulation, promotion of apoptosis or control of key tumor-relevant signaling networks. A convincing argument for a tumor-driving role of DNA methylation can be made when the same genes are also frequently mutated in cancer. Many of the most commonly hypermethylated genes encode developmental transcription factors, the methylation of which may lead to permanent gene silencing. Inactivation of such genes will deprive the cells in which the tumor may initiate from the option of undergoing or maintaining lineage differentiation and will lock them into a perpetuated stem cell-like state thus providing an additional window for cell transformation.

  1. Defined Contribution Model: Definition, Theory and an Application for Turkey

    OpenAIRE

    Metin Ercen; Deniz Gokce

    1998-01-01

    Based on a numerical application that employs social and economic parameters of the Turkish economy, this study attempts to demonstrate that the current collapse in the Turkish social security system is not unavoidable. The present social security system in Turkey is based on the defined benefit model of pension provision. On the other hand, recent proposals for reform in the social security system are based on a multipillar system, where one of the alternatives is a defined contribution pens...

  2. DEFINING SPATIAL VIOLENCE. BUCHAREST AS A STUDY CASE

    Directory of Open Access Journals (Sweden)

    Celia GHYKA

    2015-05-01

    Full Text Available The paper looks at the spatial manifestations of violence, aiming to define the category of spatial violence by focusing on the recent urban history of Bucharest; it establishes links with the longer history of natural and inflicted disasters that defined the city, and it explores the spatial, urban, social and symbolical conflicts that occured during the last 25 years, pointing at their consequences on the social and urban substance of the city.

  3. Research Network of Tehran Defined Population: Methodology and Establishment

    Directory of Open Access Journals (Sweden)

    Ali-Asghar Kolahi

    2015-12-01

    Full Text Available Background: We need a defined population for determining prevalence and incidence of diseases, as well as conducting interventional, cohort and longitudinal studies, calculating correct and timely public health indicators, assessing actual health needs of community, performing educational programs and interventions to promote healthy lifestyle, and enhancing quality of primary health services.The objective of this project was to determine a defined population which is representative of Tehran, the Capital of Iran. This article reports the methodology and establishment of the research network of Tehran defined population.Methods: This project started by selecting two urban health centers from each of the five district health centers affiliated to Shahid Beheshti University of Medical Sciences in 2012. Inside each selected urban health center, one defined population research station was established. Two new centers have been added during 2013 and 2014. For the time being, the number of the covered population of the network has reached 40000 individuals. The most important criterion for the defined population has been to be representative of the population of Tehran. For this, we selected two urban health centers from 12 of 22 municipality districts and from each of the five different socioeconomic of Greater Tehran. Merely 80000 individuals in neighborhoods of each defined population research station were considered as control group of the project.Findings: Totally we selected 12 defined population research stations and their under-covered population developed a defined population which is representative of Tehran population.Conclusion: a population lab is ready now in metropolitan of Tehran.

  4. Employing Deceptive Dynamic Network Topology Through Software-Defined Networking

    Science.gov (United States)

    2014-03-01

    actions. From [64] . . . . . 37 xi THIS PAGE INTENTIONALLY LEFT BLANK xii List of Acronyms and Abbreviations ACL Access Control List API Application...can be extremely useful in topology mapping through various latency-based geolocation methods [35], [36], [37]. PING 1 7 2 . 2 0 . 5 . 2 ( 1 7 2 . 2 0...defined northbound Applica- tion Programming Interfaces ( APIs ). Figure 3.1: Software-Defined Network Architecture. From [8] 29 3.3 SDN OpenFlow

  5. Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

    Directory of Open Access Journals (Sweden)

    McDonald Karen

    2011-08-01

    Full Text Available Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

  6. Imaging reporter gene for monitoring gene therapy

    International Nuclear Information System (INIS)

    Beco, V. de; Baillet, G.; Tamgac, F.; Tofighi, M.; Weinmann, P.; Vergote, J.; Moretti, J.L.; Tamgac, G.

    2002-01-01

    Scintigraphic images can be obtained to document gene function at cellular level. This approach is presented here and the use of a reporter gene to monitor gene therapy is described. Two main ways are presented: either the use of a reporter gene coding for an enzyme the action of which will be monitored by radiolabeled pro-drug, or a cellular receptor gene, the action of which is documented by a radio labeled cognate receptor ligand. (author)

  7. Studying the Complex Expression Dependences between Sets of Coexpressed Genes

    Directory of Open Access Journals (Sweden)

    Mario Huerta

    2014-01-01

    Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

  8. The Human Pancreas Proteome Defined by Transcriptomics and Antibody-Based Profiling

    Science.gov (United States)

    Fagerberg, Linn; Hallström, Björn M.; Schwenk, Jochen M.; Uhlén, Mathias; Korsgren, Olle; Lindskog, Cecilia

    2014-01-01

    The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects. PMID:25546435

  9. Development of a defined-sequence DNA system for use in DNA misrepair studies

    International Nuclear Information System (INIS)

    Sutton, S.; Tobias, C.A.

    1984-01-01

    The authors have developed a system that allows them to study cellular DNA repair processes at the molecular level. In particular, the authors are using this system to examine the consequences of a misrepair of radiation-induced DNA damage, as a function of dose. The cells being used are specially engineered haploid yeast cells. Maintained in the cells, at one copy per cell, is a cen plasmid, a plasmid that behaves like a functional chromosome. This plasmid carries a small defined sequence of DNA from the E. coli lac z gene. It is this lac z region (called the alpha region) that serves as the target for radiation damage. Two copies of the complimentary portion of the lac z gene are integrated into the yeast genome. Irradiated cells are screened for possible mutation in the alpha region by testing the cells' ability to hydrolyze xgal, a lactose substrate. The DNA of interest is then extracted from the cells, sequenced, and the sequence is compared to that of the control. Unlike the usual defined-sequence DNA systems, theirs is an in vivo system. A disadvantage is the relatively high background mutation rate. Results achieved with this system, as well as future applications, are discussed

  10. Exploring autophagy with Gene Ontology

    Science.gov (United States)

    2018-01-01

    ABSTRACT Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the strategies that cells use to catabolize substances in a controlled way. Autophagy is used for recycling cellular components, responding to cellular stresses and ridding cells of foreign material. Perturbations in autophagy have been implicated in a number of pathological conditions such as neurodegeneration, cardiac disease and cancer. The growing knowledge about autophagic mechanisms needs to be collected in a computable and shareable format to allow its use in data representation and interpretation. The Gene Ontology (GO) is a freely available resource that describes how and where gene products function in biological systems. It consists of 3 interrelated structured vocabularies that outline what gene products do at the biochemical level, where they act in a cell and the overall biological objectives to which their actions contribute. It also consists of ‘annotations’ that associate gene products with the terms. Here we describe how we represent autophagy in GO, how we create and define terms relevant to autophagy researchers and how we interrelate those terms to generate a coherent view of the process, therefore allowing an interoperable description of its biological aspects. We also describe how annotation of gene products with GO terms improves data analysis and interpretation, hence bringing a significant benefit to this field of study. PMID:29455577

  11. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

    Directory of Open Access Journals (Sweden)

    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  12. Sleep Health: Can We Define It? Does It Matter?

    Science.gov (United States)

    Buysse, Daniel J.

    2014-01-01

    Good sleep is essential to good health. Yet for most of its history, sleep medicine has focused on the definition, identification, and treatment of sleep problems. Sleep health is a term that is infrequently used and even less frequently defined. It is time for us to change this. Indeed, pressures in the research, clinical, and regulatory environments require that we do so. The health of populations is increasingly defined by positive attributes such as wellness, performance, and adaptation, and not merely by the absence of disease. Sleep health can be defined in such terms. Empirical data demonstrate several dimensions of sleep that are related to health outcomes, and that can be measured with self-report and objective methods. One suggested definition of sleep health and a description of self-report items for measuring it are provided as examples. The concept of sleep health synergizes with other health care agendas, such as empowering individuals and communities, improving population health, and reducing health care costs. Promoting sleep health also offers the field of sleep medicine new research and clinical opportunities. In this sense, defining sleep health is vital not only to the health of populations and individuals, but also to the health of sleep medicine itself. Citation: Buysse DJ. Sleep health: can we define it? Does it matter? SLEEP 2014;37(1):9-17. PMID:24470692

  13. Defining human death: an intersection of bioethics and metaphysics.

    Science.gov (United States)

    Manninen, Bertha Alvarez

    2009-01-01

    For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants.

  14. Positive facial expressions during retrieval of self-defining memories.

    Science.gov (United States)

    Gandolphe, Marie Charlotte; Nandrino, Jean Louis; Delelis, Gérald; Ducro, Claire; Lavallee, Audrey; Saloppe, Xavier; Moustafa, Ahmed A; El Haj, Mohamad

    2017-11-14

    In this study, we investigated, for the first time, facial expressions during the retrieval of Self-defining memories (i.e., those vivid and emotionally intense memories of enduring concerns or unresolved conflicts). Participants self-rated the emotional valence of their Self-defining memories and autobiographical retrieval was analyzed with a facial analysis software. This software (Facereader) synthesizes the facial expression information (i.e., cheek, lips, muscles, eyebrow muscles) to describe and categorize facial expressions (i.e., neutral, happy, sad, surprised, angry, scared, and disgusted facial expressions). We found that participants showed more emotional than neutral facial expressions during the retrieval of Self-defining memories. We also found that participants showed more positive than negative facial expressions during the retrieval of Self-defining memories. Interestingly, participants attributed positive valence to the retrieved memories. These findings are the first to demonstrate the consistency between facial expressions and the emotional subjective experience of Self-defining memories. These findings provide valuable physiological information about the emotional experience of the past.

  15. The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Gutiérrez Rodrigo A

    2008-09-01

    Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

  16. Novel transcripts discovered by mining genomic DNA from defined regions of bovine chromosome 6

    Directory of Open Access Journals (Sweden)

    Eberlein Annett

    2009-04-01

    Full Text Available Abstract Background Linkage analyses strongly suggest a number of QTL for production, health and conformation traits in the middle part of bovine chromosome 6 (BTA6. The identification of the molecular background underlying the genetic variation at the QTL and subsequent functional studies require a well-annotated gene sequence map of the critical QTL intervals. To complete the sequence map of the defined subchromosomal regions on BTA6 poorly covered with comparative gene information, we focused on targeted isolation of transcribed sequences from bovine bacterial artificial chromosome (BAC clones mapped to the QTL intervals. Results Using the method of exon trapping, 92 unique exon trapping sequences (ETS were discovered in a chromosomal region of poor gene coverage. Sequence identity to the current NCBI sequence assembly for BTA6 was detected for 91% of unique ETS. Comparative sequence similarity search revealed that 11% of the isolated ETS displayed high similarity to genomic sequences located on the syntenic chromosomes of the human and mouse reference genome assemblies. Nearly a third of the ETS identified similar equivalent sequences in genomic sequence scaffolds from the alternative Celera-based sequence assembly of the human genome. Screening gene, EST, and protein databases detected 17% of ETS with identity to known transcribed sequences. Expression analysis of a subset of the ETS showed that most ETS (84% displayed a distinctive expression pattern in a multi-tissue panel of a lactating cow verifying their existence in the bovine transcriptome. Conclusion The results of our study demonstrate that the exon trapping method based on region-specific BAC clones is very useful for targeted screening for novel transcripts located within a defined chromosomal region being deficiently endowed with annotated gene information. The majority of identified ETS represents unknown noncoding sequences in intergenic regions on BTA6 displaying a

  17. Crypto-rhombomeres of the mouse medulla oblongata, defined by molecular and morphological features.

    Science.gov (United States)

    Tomás-Roca, Laura; Corral-San-Miguel, Rubén; Aroca, Pilar; Puelles, Luis; Marín, Faustino

    2016-03-01

    The medulla oblongata is the caudal portion of the vertebrate hindbrain. It contains major ascending and descending fiber tracts as well as several motor and interneuron populations, including neural centers that regulate the visceral functions and the maintenance of bodily homeostasis. In the avian embryo, it has been proposed that the primordium of this region is subdivided into five segments or crypto-rhombomeres (r7-r11), which were defined according to either their parameric position relative to intersomitic boundaries (Cambronero and Puelles, in J Comp Neurol 427:522-545, 2000) or a stepped expression of Hox genes (Marín et al., in Dev Biol 323:230-247, 2008). In the present work, we examine the implied similar segmental organization of the mouse medulla oblongata. To this end, we analyze the expression pattern of Hox genes from groups 3 to 8, comparing them to the expression of given cytoarchitectonic and molecular markers, from mid-gestational to perinatal stages. As a result of this approach, we conclude that the mouse medulla oblongata is segmentally organized, similarly as in avian embryos. Longitudinal structures such as the nucleus of the solitary tract, the dorsal vagal motor nucleus, the hypoglossal motor nucleus, the descending trigeminal and vestibular columns, or the reticular formation appear subdivided into discrete segmental units. Additionally, our analysis identified an internal molecular organization of the migrated pontine nuclei that reflects a differential segmental origin of their neurons as assessed by Hox gene expression.

  18. 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.

  19. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

    Science.gov (United States)

    Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

    2017-11-01

    Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

  20. Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program.

    Science.gov (United States)

    Morrison-Nozik, Alexander; Anand, Priti; Zhu, Han; Duan, Qiming; Sabeh, Mohamad; Prosdocimo, Domenick A; Lemieux, Madeleine E; Nordsborg, Nikolai; Russell, Aaron P; MacRae, Calum A; Gerber, Anthony N; Jain, Mukesh K; Haldar, Saptarsi M

    2015-12-08

    Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.

  1. Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions.

    Science.gov (United States)

    Saha, Krishanu; Mei, Ying; Reisterer, Colin M; Pyzocha, Neena Kenton; Yang, Jing; Muffat, Julien; Davies, Martyn C; Alexander, Morgan R; Langer, Robert; Anderson, Daniel G; Jaenisch, Rudolf

    2011-11-15

    The current gold standard for the culture of human pluripotent stem cells requires the use of a feeder layer of cells. Here, we develop a spatially defined culture system based on UV/ozone radiation modification of typical cell culture plastics to define a favorable surface environment for human pluripotent stem cell culture. Chemical and geometrical optimization of the surfaces enables control of early cell aggregation from fully dissociated cells, as predicted from a numerical model of cell migration, and results in significant increases in cell growth of undifferentiated cells. These chemically defined xeno-free substrates generate more than three times the number of cells than feeder-containing substrates per surface area. Further, reprogramming and typical gene-targeting protocols can be readily performed on these engineered surfaces. These substrates provide an attractive cell culture platform for the production of clinically relevant factor-free reprogrammed cells from patient tissue samples and facilitate the definition of standardized scale-up friendly methods for disease modeling and cell therapeutic applications.

  2. Defining a caring hospital by using currently implemented survey tools.

    Science.gov (United States)

    Jennings, Nancy

    2010-09-01

    Health care organizations are constantly striving to provide a more cost-effective and higher quality treatment within a caring environment. However, balancing the demands of regulatory agencies with the holistic needs of the patient is challenging. Further challenging is how to define those hospitals that provide an exceptional caring environment for their patients. By using survey tools that are already being administered in hospital settings, the opportunity exists to analyze the results obtained from these tools to define a hospital as a caring organization without the added burden of separate data collection.

  3. Software-Defined Radio Demonstrators: An Example and Future Trends

    Directory of Open Access Journals (Sweden)

    Ronan Farrell

    2009-01-01

    Full Text Available Software-defined radio requires the combination of software-based signal processing and the enabling hardware components. In this paper, we present an overview of the criteria for such platforms and the current state of development and future trends in this area. This paper will also provide details of a high-performance flexible radio platform called the maynooth adaptable radio system (MARS that was developed to explore the use of software-defined radio concepts in the provision of infrastructure elements in a telecommunications application, such as mobile phone basestations or multimedia broadcasters.

  4. A Formal Model and Verification Problems for Software Defined Networks

    Directory of Open Access Journals (Sweden)

    V. A. Zakharov

    2013-01-01

    Full Text Available Software-defined networking (SDN is an approach to building computer networks that separate and abstract data planes and control planes of these systems. In a SDN a centralized controller manages a distributed set of switches. A set of open commands for packet forwarding and flow-table updating was defined in the form of a protocol known as OpenFlow. In this paper we describe an abstract formal model of SDN, introduce a tentative language for specification of SDN forwarding policies, and set up formally model-checking problems for SDN.

  5. Optimization of the Actuarial Model of Defined Contribution Pension Plan

    Directory of Open Access Journals (Sweden)

    Yan Li

    2014-01-01

    Full Text Available The paper focuses on the actuarial models of defined contribution pension plan. Through assumptions and calculations, the expected replacement ratios of three different defined contribution pension plans are compared. Specially, more significant considerable factors are put forward in the further cost and risk analyses. In order to get an assessment of current status, the paper finds a relationship between the replacement ratio and the pension investment rate using econometrics method. Based on an appropriate investment rate of 6%, an expected replacement ratio of 20% is reached.

  6. Defining a region of optimization based on engine usage data

    Science.gov (United States)

    Jiang, Li; Lee, Donghoon; Yilmaz, Hakan; Stefanopoulou, Anna

    2015-08-04

    Methods and systems for engine control optimization are provided. One or more operating conditions of a vehicle engine are detected. A value for each of a plurality of engine control parameters is determined based on the detected one or more operating conditions of the vehicle engine. A range of the most commonly detected operating conditions of the vehicle engine is identified and a region of optimization is defined based on the range of the most commonly detected operating conditions of the vehicle engine. The engine control optimization routine is initiated when the one or more operating conditions of the vehicle engine are within the defined region of optimization.

  7. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

    Energy Technology Data Exchange (ETDEWEB)

    Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

    2013-10-01

    The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

  8. Define the Twist-ATX-LPAR1 Signaling Axis in Promoting Obesity Associated Triple Negative Breast Cancer

    Science.gov (United States)

    2017-05-01

    original proposal and as defined in the statement of work . 6. Products We have generated mice with tissue specific inactivation of the ENPP2 gene in...Kentucky College of Medicine 5e. TASK NUMBER E-Mail: yiwei.lin@uky.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8...ABSTRACT Breast cancer remains the second leading cause of cancer‐related death in women worldwide. Triple negative breast cancer (TNBC) carries a poorer

  9. NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

    Science.gov (United States)

    Normal Nasal Gene Expression Levels Using cDNA Array Technology. The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

  10. Gene doping: an overview and current implications for athletes

    NARCIS (Netherlands)

    van der Gronde, T.; de Hon, O.; Haisma, H.J.; Pieters, T.

    2013-01-01

    The possibility of gene doping, defined as the transfer of nucleic acid sequences and/or the use of normal or genetically modified cells to enhance sport performance, is a real concern in sports medicine. The abuse of knowledge and techniques gained in the area of gene therapy is a form of doping,

  11. Gene doping : an overview and current implications for athletes

    NARCIS (Netherlands)

    van der Gronde, Toon; de Hon, Olivier; Haisma, Hidde J.; Pieters, Toine

    The possibility of gene doping, defined as the transfer of nucleic acid sequences and/or the use of normal or genetically modified cells to enhance sport performance, is a real concern in sports medicine. The abuse of knowledge and techniques gained in the area of gene therapy is a form of doping,

  12. Candidate Gene Identification of Flowering Time Genes in Cotton

    Directory of Open Access Journals (Sweden)

    Corrinne E. Grover

    2015-07-01

    Full Text Available Flowering time control is critically important to all sexually reproducing angiosperms in both natural ecological and agronomic settings. Accordingly, there is much interest in defining the genes involved in the complex flowering-time network and how these respond to natural and artificial selection, the latter often entailing transitions in day-length responses. Here we describe a candidate gene analysis in the cotton genus , which uses homologs from the well-described flowering network to bioinformatically and phylogenetically identify orthologs in the published genome sequence from Ulbr., one of the two model diploid progenitors of the commercially important allopolyploid cottons, L. and L. Presence and patterns of expression were evaluated from 13 aboveground tissues related to flowering for each of the candidate genes using allopolyploid as a model. Furthermore, we use a comparative context to determine copy number variability of each key gene family across 10 published angiosperm genomes. Data suggest a pattern of repeated loss of duplicates following ancient whole-genome doubling events in diverse lineages. The data presented here provide a foundation for understanding both the parallel evolution of day-length neutrality in domesticated cottons and the flowering-time network, in general, in this important crop plant.

  13. Defining the biological bases of individual differences in musicality

    NARCIS (Netherlands)

    Gingras, B.; Honing, H.; Peretz, I.; Trainor, L.J.; Fisher, S.E.

    2015-01-01

    Advances in molecular technologies make it possible to pinpoint genomic factors associated with complex human traits. For cognition and behaviour, identification of underlying genes provides new entry points for deciphering the key neurobiological pathways. In the past decade, the search for genetic

  14. Defining 'plain language' in contemporary South Africa | Cornelius ...

    African Journals Online (AJOL)

    Defining the concept 'plain language' has been hugely problematic since the origins of the socalled Plain Language Movement in the 1970s in the United States and elsewhere in the world. Definitions of 'plain language' abound, yet James (2008: 6) warns, in relation to plain language practitioners, that “we can't yet call ...

  15. Defining Success in Action Learning: An International Comparison

    Science.gov (United States)

    Bong, Hyeon-Cheol; Cho, Yonjoo

    2017-01-01

    Purpose: The purpose of this paper was to explore how the two groups of action learning experts (Korean and non-Korean experts) define success of action learning to see whether there are any cultural differences. To this end, the authors conducted a total of 44 interviews with action learning experts around the world. Research questions guiding…

  16. 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. ...

  17. Toward Edge-Defined Holey Boron Nitride Nanosheets

    Science.gov (United States)

    Lin, Yi; Liao, Yunlong; Chen, Zhongfan; Connell, John W.

    2015-01-01

    "Holey" two-dimensional (2D) nanosheets with well-defined holy morphology and edge chemistry are highly desirable for applications such as energy storage, catalysis, sensing, transistors, and molecular transport/separation. For example, holey grapheme is currently under extensive investigation for energy storage applications because of the improvement in ion transport due to through the thickness pathways provided by the holes. Without the holes, the 2D materials have significant limitations for such applications in which efficient ion transport is important. As part of an effort to apply this approach to other 2D nanomaterials, a method to etch geometrically defined pits or holes on the basal plane surface of hexagonal boron nitride (h-BN) nanosheets has been developed. The etching, conducted via heating in ambient air using metal nanoparticles as catalysts, was facile, controllable, and scalable. Starting h-BN layered crystals were etched and subsequently exfoliated into boron nitride nanosheets (BNNSs). The as-etched and exfoliated h-BN nanosheets possessed defined pit and hole shapes that were comprised of regulated nanostructures at the edges. The current finding are the first step toward the bulk preparation of holey BNNSs with defined holes and edges.

  18. Farm elders define health as the ability to work.

    Science.gov (United States)

    Reed, Deborah B; Rayens, Mary Kay; Conley, Christina K; Westneat, Susan; Adkins, Sarah M

    2012-08-01

    Thirty percent of America's 2.2 million farms are operated by individuals older than 65 years. This study examined how older farmers define health and determined whether demographic characteristics, farm work, and physical and mental health status predict health definition. Data were collected via telephone and mailed surveys during the baseline wave of data collection in a longitudinal study of family farmers residing in two southern states (n=1,288). Nearly 42% defined health as the "ability to work" compared to a physical health-related definition. Predictors of defining health as the ability to work included being White, performing more farm tasks in the past week, taking prescription medications daily, and having minimal health-related limitations to farm work. Health behaviors are centered on the individual's perception of health. Understanding the defining attributes of health can support better approaches to health care and health promotion, particularly among rural subcultures such as farmers, whose identity is rooted in their work. Copyright 2012, SLACK Incorporated.

  19. Anger, hatred, or just heartlessness?: Defining gratuitous violence ...

    African Journals Online (AJOL)

    Violent crime in South Africa is sometimes said to be unusual, because it is perceived to frequently be gratuitous. This article engages with the question of how to define gratuitous violence. If the term gratuitous is understood to mean 'for nothing', gratuitous violence should be understood as violence that is 'low on ...

  20. 45 CFR 506.10 - “Vietnam conflict” defined.

    Science.gov (United States)

    2010-10-01

    ... § 506.10 “Vietnam conflict” defined. Vietnam conflict refers to the period beginning February 28, 1961... “Vietnam conflict” for purposes of payment of interest on missing military service members' deposits in the... ending date for the Vietnam conflict for purposes of determining eligibility for compensation under 50 U...

  1. 40 CFR 68.33 - Defining offsite impacts-environment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Defining offsite impacts-environment. 68.33 Section 68.33 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... impacts—environment. (a) The owner or operator shall list in the RMP environmental receptors within a...

  2. Defining a Progress Metric for CERT RMM Improvement

    Science.gov (United States)

    2017-09-14

    REV-03.18.2016.0 Defining a Progress Metric for CERT-RMM Improvement Gregory Crabb Nader Mehravari David Tobar September 2017 TECHNICAL ...fendable resource allocation decisions. Technical metrics measure aspects of controls implemented through technology (systems, soft- ware, hardware...implementation metric would be the percentage of users who have received anti-phishing training . • Effectiveness/efficiency metrics measure whether

  3. 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

  4. 29 CFR 779.221 - “Common control” defined.

    Science.gov (United States)

    2010-07-01

    ... organizational units.” The meaning of “common control” is discussed comprehensively in part 776 of this chapter. ... Or Common Control § 779.221 “Common control” defined. Under the definition the “enterprise” includes all related activities performed through “common control” for a common business purpose. The word...

  5. 38 CFR 17.31 - Duty periods defined.

    Science.gov (United States)

    2010-07-01

    ... Definitions and Active Duty § 17.31 Duty periods defined. Full-time duty as a member of the Women's Army Auxiliary Corps, Women's Reserve of the Navy and Marine Corps and Women's Reserve of the Coast Guard. [34 FR..., 1996, § 17.31(b)(5) was redesignated as § 17.31. Protection of Patient Rights ...

  6. Properties of dual codes defined by nondegenerate forms

    Directory of Open Access Journals (Sweden)

    Steve Szabo

    2017-01-01

    Full Text Available Dual codes are defined with respect to non-degenerate sesquilinear or bilinear forms over a finite Frobenius ring. These dual codes have the properties one expects from a dual code: they satisfy a double-dual property, they have cardinality complementary to that of the primal code, and they satisfy the MacWilliams identities for the Hamming weight.

  7. Defining, Developing, and Measuring "Proclivities for Teaching Mathematics"

    Science.gov (United States)

    Lewis, Jennifer M.; Fischman, Davida; Riggs, Matt

    2015-01-01

    This article presents a form of teacher reasoning that we call "proclivities for teaching mathematics." We define proclivities for teaching mathematics as the beliefs, knowledge, and dispositions that are actionable in the flow of instruction, and we argue that growth in this area contributes to positive change in mathematics…

  8. 40 CFR 68.30 - Defining offsite impacts-population.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Defining offsite impacts-population. 68.30 Section 68.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... impacts—population. (a) The owner or operator shall estimate in the RMP the population within a circle...

  9. What Does "Apple" Mean? Learning To Define Words.

    Science.gov (United States)

    Marinellie, Sally A.

    2001-01-01

    This article discusses the importance of learning to define a word. It provides a brief background on the contribution of the definitional skills to communication and school success, information on children's development of definitions, and teacher and family strategies for enhancing young children's definitions in relation to other skills.…

  10. Undergraduate Performance in Solving Ill-Defined Biochemistry Problems

    Science.gov (United States)

    Sensibaugh, Cheryl A.; Madrid, Nathaniel J.; Choi, Hye-Jeong; Anderson, William L.; Osgood, Marcy P.

    2017-01-01

    With growing interest in promoting skills related to the scientific process, we studied performance in solving ill-defined problems demonstrated by graduating biochemistry majors at a public, minority-serving university. As adoption of techniques for facilitating the attainment of higher-order learning objectives broadens, so too does the need to…

  11. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...... conjugates and their use in vaccination, production of antibodies, high throughput screening, diagnostic assays and libraries....

  12. Responsibility for proving and defining in abstract algebra class

    Science.gov (United States)

    Fukawa-Connelly, Timothy

    2016-07-01

    There is considerable variety in inquiry-oriented instruction, but what is common is that students assume roles in mathematical activity that in a traditional, lecture-based class are either assumed by the teacher (or text) or are not visible at all in traditional math classrooms. This paper is a case study of the teaching of an inquiry-based undergraduate abstract algebra course. In particular, gives a theoretical account of the defining and proving processes. The study examines the intellectual responsibility for the processes of defining and proving that the professor devolved to the students. While the professor wanted the students to engage in all aspects of defining and proving, he was only successful at devolving responsibility for certain aspects and much more successful at devolving responsibility for proving than conjecturing or defining. This study suggests that even a well-intentioned instructor may not be able to devolve responsibility to students for some aspects of mathematical practice without using a research-based curriculum or further professional development.

  13. Towards an ontological model defining the social engineering domain

    CSIR Research Space (South Africa)

    Mouton, F

    2014-08-01

    Full Text Available -1 ICT and Society IFIP Advances in Information and Communication Technology Volume 431, 2014, pp 266- 279 Towards an Ontological Model Defining the Social Engineering Domain Francois Mouton 1 , Louise Leenen 1 , Mercia M. Malan 2 , and H...

  14. Implementation of a user defined mine blast model in LSDYNA

    NARCIS (Netherlands)

    Tyler-Street, M.; Leerdam, P.J.C.

    2012-01-01

    A user defined mine blast model has been developed and implemented into the explicit finite element code LS-DYNA to provide a numerically efficient method for simulating an antivehicular mine blast. The objective is to provide a simple and robust numerical method which is able to represent both the

  15. A Generalized Approach to Defining Item Discrimination for DCMs

    Science.gov (United States)

    Henson, Robert; DiBello, Lou; Stout, Bill

    2018-01-01

    Diagnostic classification models (DCMs, also known as cognitive diagnosis models) hold the promise of providing detailed classroom information about the skills a student has or has not mastered. Specifically, DCMs are special cases of constrained latent class models where classes are defined based on mastery/nonmastery of a set of attributes (or…

  16. INTRODUCTION Dental care utilization can be defined as the ...

    African Journals Online (AJOL)

    INTRODUCTION. Dental care utilization can be defined as the percentage of the population who access dental services over a specified period of time1. Measures of actual dental care utilization describe the percentage of the population who have seen a dentist at different time intervals. Dental disease is a serious public ...

  17. Frameworks for defining and managing the wilderness experience

    Science.gov (United States)

    Robert E. Manning

    2012-01-01

    A large and growing body of research on outdoor recreation and the wilderness experience has been conducted over the nearly 50 years since passage of the Wilderness Act of 1964. A number of conceptual and empirical frameworks have emerged from this body of knowledge that can be used to help define and manage the wilderness experience.

  18. A Neurogenetics Approach to Defining Differential Susceptibility to Institutional Care

    Science.gov (United States)

    Brett, Zoe H.; Sheridan, Margaret; Humphreys, Kate; Smyke, Anna; Gleason, Mary Margaret; Fox, Nathan; Zeanah, Charles; Nelson, Charles; Drury, Stacy

    2015-01-01

    An individual's neurodevelopmental and cognitive sequelae to negative early experiences may, in part, be explained by genetic susceptibility. We examined whether extreme differences in the early caregiving environment, defined as exposure to severe psychosocial deprivation associated with institutional care compared to normative rearing,…

  19. Defining care products to finance health care in the Netherlands

    NARCIS (Netherlands)

    M. Westerdijk (MacHiel); J.J. Zuurbier (Joost); M. Ludwig (Martijn); S. Prins (Sarah)

    2012-01-01

    textabstractA case-mix project started in the Netherlands with the primary goal to define a complete set of health care products for hospitals. The definition of the product structure was completed 4 years later. The results are currently being used for billing purposes. This paper focuses on the

  20. 75 FR 70625 - Annual Funding Notice for Defined Benefit Plans

    Science.gov (United States)

    2010-11-18

    ... model funding notices. Much of the guidance in FAB 2009-01 has been incorporated into the proposed... Annual Funding Notice for Defined Benefit Plans AGENCY: Employee Benefits Security Administration, Labor... implement the annual funding notice requirement in the Employee Retirement Income Security Act of 1974...

  1. Mitigating the controller performance bottlenecks in Software Defined Networks

    DEFF Research Database (Denmark)

    Caba, Cosmin Marius; Soler, José

    2016-01-01

    The centralization of the control plane decision logic in Software Defined Networking (SDN) has raised concerns regarding the performance of the SDN Controller (SDNC) when the network scales up. A number of solutions have been proposed in the literature to address these concerns. This paper...

  2. Five-Star Schools: Defining Quality in Early Childhood Programs

    Science.gov (United States)

    Hertzog, Nancy B.

    2012-01-01

    Hakeem, Emily, Jose, and Latisha are all entering preschool in the fall. Their mothers are looking for the highest quality early childhood program they can find. Is there a guide for them to find a five-star program? Are all certified or accredited programs of equal quality? How do these parents and guardians know what defines quality in early…

  3. The Devil Is in the Details: Defining Civic Engagement

    Science.gov (United States)

    Brabant, Margaret; Braid, Donald

    2009-01-01

    For "civic engagement" work to have meaningful and long-term impact upon students, partners, and postsecondary institutions, each institution must undertake the difficult work of defining civic engagement for itself such that the definition aligns with the institution's educational mission and local context. We argue that civic…

  4. Defining collaborative business rules management solutions : framework and method

    NARCIS (Netherlands)

    dr. Martijn Zoet; Johan Versendaal

    2014-01-01

    From the publishers' website: The goal of this research is to define a method for configuring a collaborative business rules management solution from a value proposition perspective. In an earlier published study (Business rules management solutions: added value by means of business

  5. 19 CFR 10.175 - Imported directly defined.

    Science.gov (United States)

    2010-04-01

    ... imported directly only if they: (1) Remained under the control of the customs authority of the intermediate... 19 Customs Duties 1 2010-04-01 2010-04-01 false Imported directly defined. 10.175 Section 10.175 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

  6. Defining the Shoah: An Opening Lesson for a Holocaust Unit

    Science.gov (United States)

    Lindquist, David H.

    2013-01-01

    Students often bring considerable prior information about the Holocaust to their study of the event, with much of that knowledge being inaccurate or incomplete. In addition, the Shoah's complexity necessitates that teachers establish a well-defined framework as they introduce the topic to their students. This article outlines an opening lesson for…

  7. Development of an automated desktop procedure for defining macro ...

    African Journals Online (AJOL)

    methods (Von Neumann mean square error, CUSUM plots or unweighted values and the Worsley Likelihood Ratio Test (WLRT)) were used to define macro-reach breaks for four South African rivers (Crocodile, Olifants, Mhlathuze and Seekoei Rivers) and were compared to ... Water SA Vol.32 (3) 2006: pp.395-402 ...

  8. Women's Leadership Development: A Study of Defining Moments

    Science.gov (United States)

    Dahlvig, Jolyn E.; Longman, Karen A.

    2010-01-01

    This article reports the findings of a grounded theory study of "defining moments" that were described as pivotal in the personal and professional journeys of women who had been identified as emerging leaders within Christian higher education. Analysis of transcripts from interviews with 16 participants in a Women's Leadership Development…

  9. Defining Leadership: Collegiate Women's Learning Circles: A Qualitative Approach

    Science.gov (United States)

    Preston-Cunningham, Tammie; Elbert, Chanda D.; Dooley, Kim E.

    2017-01-01

    The researchers employed qualitative methods to evaluate first-year female students' definition of "leadership" through involvement in the Women's Learning Circle. The findings revealed that students defined leadership in two dimensions: traits and behaviors. The qualitative findings explore a multidimensional approach to the voices of…

  10. How Do Deaf Adults Define Quality of Life?

    Science.gov (United States)

    McAbee, Emilee R.; Drasgow, Erik; Lowrey, K. Alisa

    2017-01-01

    Six deaf adults defined quality of life (QOL) in personal interviews. Questions were based on an eight-domain QOL framework: physical well-being, emotional well-being, interpersonal relations, social inclusion, personal development, material well-being, self-determination, and rights (Schalock & Alonso, 2002). The interview process had three…

  11. 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)

  12. AppNVM: Software-Defined, Application_Driven SSD

    DEFF Research Database (Denmark)

    Bjørling, Matias; Madsen, Jesper; Gonzalez, Javier

    2015-01-01

    -NVM SSDs by installing rules, which define (i) the logical address space exposed to the application, and (ii) how application requests are handled. A controller then transforms those rules and installs them onto the device, enforcing permissions and global policies such as wear-leveling and garbage...

  13. Duplicability of self-interacting human genes.

    LENUS (Irish Health Repository)

    Pérez-Bercoff, Asa

    2010-01-01

    BACKGROUND: There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS: We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS: Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.

  14. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  15. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  16. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Wiebe, Leonard I.

    1997-01-01

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

  17. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  18. G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes

    Directory of Open Access Journals (Sweden)

    Lemay Danielle G

    2012-09-01

    Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The

  19. Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

    Science.gov (United States)

    Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

    2015-01-01

    Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

  20. Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

    Directory of Open Access Journals (Sweden)

    Boris P Hejblum

    2015-06-01

    Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

  1. Defining the end-point of mastication: A conceptual model.

    Science.gov (United States)

    Gray-Stuart, Eli M; Jones, Jim R; Bronlund, John E

    2017-10-01

    The great risks of swallowing are choking and aspiration of food into the lungs. Both are rare in normal functioning humans, which is remarkable given the diversity of foods and the estimated 10 million swallows performed in a lifetime. Nevertheless, it remains a major challenge to define the food properties that are necessary to ensure a safe swallow. Here, the mouth is viewed as a well-controlled processor where mechanical sensory assessment occurs throughout the occlusion-circulation cycle of mastication. Swallowing is a subsequent action. It is proposed here that, during mastication, temporal maps of interfacial property data are generated, which the central nervous system compares against a series of criteria in order to be sure that the bolus is safe to swallow. To determine these criteria, an engineering hazard analysis tool, alongside an understanding of fluid and particle mechanics, is used to deduce the mechanisms by which food may deposit or become stranded during swallowing. These mechanisms define the food properties that must be avoided. By inverting the thinking, from hazards to ensuring safety, six criteria arise which are necessary for a safe-to-swallow bolus. A new conceptual model is proposed to define when food is safe to swallow during mastication. This significantly advances earlier mouth models. The conceptual model proposed in this work provides a framework of decision-making to define when food is safe to swallow. This will be of interest to designers of dietary foods, foods for dysphagia sufferers and will aid the further development of mastication robots for preparation of artificial boluses for digestion research. It enables food designers to influence the swallow-point properties of their products. For example, a product may be designed to satisfy five of the criteria for a safe-to-swallow bolus, which means the sixth criterion and its attendant food properties define the swallow-point. Alongside other organoleptic factors, these

  2. To Define or Not to Define; Implications for the Governability of Small-Scale coastal Fisheries in the Netherlands

    NARCIS (Netherlands)

    Vos, de B.I.; Kraan, M.L.

    2015-01-01

    This chapter discusses the need to define the small-scale coastal fisheries sector in the Netherlands. It shows that the fact that there is no clear definition of what small-scale fisheries is, affects its governability. This seems to go hand in hand with the lack of a clear perspective on what the

  3. Gene doping: gene delivery for olympic victory.

    Science.gov (United States)

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  4. Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes

    KAUST Repository

    Alam, Tanvir; Medvedeva, Yulia A.; Jia, Hui; Brown, James B.; Lipovich, Leonard; Bajic, Vladimir B.

    2014-01-01

    raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted

  5. Analytical and computational approaches to define the Aspergillus niger secretome

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, Adrian; Butler, Gregory D.; Powlowski, Justin; Panisko, Ellen A.; Baker, Scott E.

    2009-03-01

    We used computational and mass spectrometric approaches to characterize the Aspergillus niger secretome. The 11,200 gene models predicted in the genome of A. niger strain ATCC 1015 were the data source for the analysis. Depending on the computational methods used, 691 to 881 proteins were predicted to be secreted proteins. We cultured A. niger in six different media and analyzed the extracellular proteins produced using mass spectrometry. A total of 222 proteins were identified, with 39 proteins expressed under all six conditions and 74 proteins expressed under only one condition. The secreted proteins identified by mass spectrometry were used to guide the correction of about 20 gene models. Additional analysis focused on extracellular enzymes of interest for biomass processing. Of the 63 glycoside hydrolases predicted to be capable of hydrolyzing cellulose, hemicellulose or pectin, 94% of the exo-acting enzymes and only 18% of the endo-acting enzymes were experimentally detected.

  6. Deconstructing mammalian reproduction: using knockouts to define fertility pathways.

    Science.gov (United States)

    Roy, Angshumoy; Matzuk, Martin M

    2006-02-01

    Reproduction is the sine qua non for the propagation of species and continuation of life. It is a complex biological process that is regulated by multiple factors during the reproductive life of an organism. Over the past decade, the molecular mechanisms regulating reproduction in mammals have been rapidly unraveled by the study of a vast number of mouse gene knockouts with impaired fertility. The use of reverse genetics to generate null mutants in mice through targeted disruption of specific genes has enabled researchers to identify essential regulators of spermatogenesis and oogenesis in vivo and model human disorders affecting reproduction. This review focuses on the merits, utility, and the variations of the knockout technology in studies of reproduction in mammals.

  7. Distinct cardiac transcriptional profiles defining pregnancy and exercise.

    Directory of Open Access Journals (Sweden)

    Eunhee Chung

    Full Text Available BACKGROUND: Although the hypertrophic responses of the heart to pregnancy and exercise are both considered to be physiological processes, they occur in quite different hormonal and temporal settings. In this study, we have compared the global transcriptional profiles of left ventricular tissues at various time points during the progression of hypertrophy in exercise and pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: The following groups of female mice were analyzed: non-pregnant diestrus cycle sedentary control, mid-pregnant, late-pregnant, and immediate-postpartum, and animals subjected to 7 and 21 days of voluntary wheel running. Hierarchical clustering analysis shows that while mid-pregnancy and both exercise groups share the closest relationship and similar gene ontology categories, late pregnancy and immediate post-partum are quite different with high representation of secreted/extracellular matrix-related genes. Moreover, pathway-oriented ontological analysis shows that metabolism regulated by cytochrome P450 and chemokine pathways are the most significant signaling pathways regulated in late pregnancy and immediate-postpartum, respectively. Finally, increases in expression of components of the proteasome observed in both mid-pregnancy and immediate-postpartum also result in enhanced proteasome activity. Interestingly, the gene expression profiles did not correlate with the degree of cardiac hypertrophy observed in the animal groups, suggesting that distinct pathways are employed to achieve similar amounts of cardiac hypertrophy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that cardiac adaptation to the later stages of pregnancy is quite distinct from both mid-pregnancy and exercise. Furthermore, it is very dynamic since, by 12 hours post-partum, the heart has already initiated regression of cardiac growth, and 50 genes have changed expression significantly in the immediate-postpartum compared to late-pregnancy. Thus, pregnancy

  8. Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.

    Science.gov (United States)

    Fridley, Brooke L; Batzler, Anthony; Li, Liang; Li, Fang; Matimba, Alice; Jenkins, Gregory D; Ji, Yuan; Wang, Liewei; Weinshilboum, Richard M

    2011-11-01

    Responses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. A gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine]. The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.

  9. Critical defining characteristics for nursing diagnosis about ineffective breastfeeding

    Directory of Open Access Journals (Sweden)

    Sandra Cristina de Alvarenga

    Full Text Available ABSTRACT Objective: To investigate the Nursing diagnostic accuracy measures and to propose a model to use defining characteristics in order to judge the nursing diagnosis of ineffective breastfeeding. Method: Cross-sectional study with a sample of 73 binomials mom-child hospitalized in a maternity ward of an University Hospital, from July to August of 2014. Results: The diagnostic predominance rate was 58.9%. The characteristics that best meet the needs of logistic regression model were: discontinuance of breast sucking; infant's inability of seizing the areola-nipple region correctly; infant's crying one hour after breastfeeding and inappropriate milk supply perceived. Conclusion: Breastfeeding process is dynamic; diagnostic judgement may suffer some changes according to the time data are collected; the defining characteristics are the best predictors if associated with models and rules of use.

  10. Memory Synapses Are Defined by Distinct Molecular Complexes: A Proposal.

    Science.gov (United States)

    Sossin, Wayne S

    2018-01-01

    Synapses are diverse in form and function. While there are strong evidential and theoretical reasons for believing that memories are stored at synapses, the concept of a specialized "memory synapse" is rarely discussed. Here, we review the evidence that memories are stored at the synapse and consider the opposing possibilities. We argue that if memories are stored in an active fashion at synapses, then these memory synapses must have distinct molecular complexes that distinguish them from other synapses. In particular, examples from Aplysia sensory-motor neuron synapses and synapses on defined engram neurons in rodent models are discussed. Specific hypotheses for molecular complexes that define memory synapses are presented, including persistently active kinases, transmitter receptor complexes and trans-synaptic adhesion proteins.

  11. Defining The Energy Saving Potential of Architectural Design

    DEFF Research Database (Denmark)

    Naboni, Emanuele; Malcangi, Antonio; Zhang, Yi

    2015-01-01

    Designers, in response to codes or voluntary " green building " programs, are increasingly concerned with building energy demand reduction, but they are not fully aware of the energy saving potential of architectural design. According to literature, building form, construction and material choices...... on sustainable design: " Design With Climate " by Olgyay (1963), which discussed strategies for climate-adapted architecture, and Lechner´s " Heating, Cooling and Lighting " (1991), on how to reduce building energy needs by as much as 60 – 80 percent with proper architectural design decisions. Both books used...... behaviour. The research shows the best solution for each of the climates and compares them with Olgyay´s findings. Finally, for each climate the energy saving potential is defined and then compared to Lechner's conclusions. Defining The Energy Saving Potential of Architectural Design (PDF Download Available...

  12. Defining the complement biomarker profile of c3 glomerulopathy

    DEFF Research Database (Denmark)

    Zhang, Yuzhou; Nester, Carla M; Martin, Bertha

    2014-01-01

    BACKGROUND AND OBJECTIVES: C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway......, although a full description of the disease spectrum remains to be determined. This study sought to validate and define the association of complement dysregulation with C3G and to determine whether specific complement pathway abnormalities could inform disease definition. DESIGN, SETTING, PARTICIPANTS......, & MEASUREMENTS: This study included 34 patients with C3G (17 with C3 glomerulonephritis [C3GN] and 17 with dense deposit disease [DDD]) diagnosed between 2008 and 2013 selected from the C3G Registry. Control samples (n=100) were recruited from regional blood drives. Nineteen complement biomarkers were assayed...

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Defining Parents, Making Citizens: Nationality and Citizenship in Transnational Surrogacy.

    Science.gov (United States)

    Deomampo, Daisy

    2015-01-01

    Over the past decade, India has attracted would-be parents from around the globe, many seeking to build their families through gestational surrogacy. Through extensive ethnographic fieldwork in India, I found that issues of nationality and citizenship for babies born via gestational surrogacy were among the most pressing concerns for commissioning parents. In this article, I consider the ways in which states and institutions define parents and make citizens, as well as how families created through surrogacy in India challenge these processes in new ways. By closely interrogating the ways that families, states, and global and local institutions define parenthood and citizenship within the context of transnational surrogacy, I show that while transnational surrogacy may challenge conventional understandings of kinship and family, it simultaneously renaturalizes state definitions of citizenship and motherhood.

  15. Simulation of speckle patterns with pre-defined correlation distributions

    Science.gov (United States)

    Song, Lipei; Zhou, Zhen; Wang, Xueyan; Zhao, Xing; Elson, Daniel S.

    2016-01-01

    We put forward a method to easily generate a single or a sequence of fully developed speckle patterns with pre-defined correlation distribution by utilizing the principle of coherent imaging. The few-to-one mapping between the input correlation matrix and the correlation distribution between simulated speckle patterns is realized and there is a simple square relationship between the values of these two correlation coefficient sets. This method is demonstrated both theoretically and experimentally. The square relationship enables easy conversion from any desired correlation distribution. Since the input correlation distribution can be defined by a digital matrix or a gray-scale image acquired experimentally, this method provides a convenient way to simulate real speckle-related experiments and to evaluate data processing techniques. PMID:27231589

  16. 2D nanomaterials assembled from sequence-defined molecules

    International Nuclear Information System (INIS)

    Mu, Peng; State University of New York; Zhou, Guangwen; Chen, Chun-Long

    2017-01-01

    Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges and opportunities in this new field.

  17. Defining culturally responsive teaching: The case of mathematics

    Directory of Open Access Journals (Sweden)

    Jenni L. Harding-DeKam

    2014-12-01

    Full Text Available Elementary classroom teachers in eight school districts across Colorado, United States, share the knowledge of their students’ home and community life, define culturally responsive mathematics based on the children they instruct, and give examples of how students learn math through culture in their classrooms. Findings from two interviews, classroom observations, and student artifacts reveal that teachers have an intimate cultural knowledge of the students in their classrooms, define culturally responsive mathematical practices consistent with research, use culturally responsive mathematics teaching for authentic learning, and express a need for additional professional development and curriculum support for culturally responsive mathematics instruction. Culturally responsive mathematics is important in elementary classrooms because it allows students to make personal connections to mathematics content.

  18. 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.

  19. Reconfigurable network systems and software-defined networking

    OpenAIRE

    Zilberman, N.; Watts, P. M.; Rotsos, C.; Moore, A. W.

    2015-01-01

    Modern high-speed networks have evolved from relatively static networks to highly adaptive networks facilitating dynamic reconfiguration. This evolution has influenced all levels of network design and management, introducing increased programmability and configuration flexibility. This influence has extended from the lowest level of physical hardware interfaces to the highest level of network management by software. A key representative of this evolution is the emergence of software-defined n...

  20. Software defined networks reactive flow programming and load balance switching

    OpenAIRE

    Καλλιανιώτης, Νικόλαος; Kallianiotis, Nikolaos

    2017-01-01

    This project serves as a Master Thesis as the requirements of the master’s programme Master of Digital Communications and Networks. It proposes load balancing algorithms applied to Software-Defined Networks to achieve the best possible resource utilisation of each of the links present in a network. The open-sources Opendaylight project and Floodlight project are used as SDN controllers, and the network is emulated using Mininet software

  1. Stability analysis of switched linear systems defined by graphs

    OpenAIRE

    Athanasopoulos, Nikolaos; Lazar, Mircea

    2015-01-01

    We present necessary and sufficient conditions for global exponential stability for switched discrete-time linear systems, under arbitrary switching, which is constrained within a set of admissible transitions. The class of systems studied includes the family of systems under arbitrary switching, periodic systems, and systems with minimum and maximum dwell time specifications. To reach the result, we describe the set of rules that define the admissible transitions with a weighted directed gra...

  2. Defining Process Performance Indicators By Using Templates and Patterns

    OpenAIRE

    Río Ortega, Adela del; Resinas Arias de Reyna, Manuel; Durán Toro, Amador; Ruiz Cortés, Antonio

    2012-01-01

    Process Performance Indicators (PPIs) are a key asset for the mea- 2 surement of the achievement of strategic and operational goals in process–oriented 3 organisations. Ideally, the definition of PPIs should not only be unambiguous, 4 complete, and understandable to non–technical stakeholders, but also traceable 5 to business processes and verifiable by means of automated analysis. in practice, 6 PPIs are defined either informally in natural language, with its well–known prob- 7 lems, or at a...

  3. Defining Nano, Nanotechnology and Nanomedicine: Why Should It Matter?

    OpenAIRE

    Satalkar Priya; Elger Bernice Simone; Shaw David M

    2016-01-01

    Nanotechnology which involves manipulation of matter on a 'nano' scale is considered to be a key enabling technology. Medical applications of nanotechnology (commonly known as nanomedicine) are expected to significantly improve disease diagnostic and therapeutic modalities and subsequently reduce health care costs. However there is no consensus on the definition of nanotechnology or nanomedicine and this stems from the underlying debate on defining 'nano'. This paper aims to present the diver...

  4. Safety Leadership Defined within the Australian Construction Industry

    OpenAIRE

    Daniel, Luke

    2015-01-01

    This research explores the tenets of safety leadership within the Australian construction environment. The scope of this research aims to establish a universal definition of safety leadership and how it differs from other leadership disciplines. The literature review into this topic was governed by the parent disciplines of Safety and Leadership.  Gaps were identified in the literature that indicated safety leadership is not a well-defined concept and much of the work into safety leadership h...

  5. Traffic Policing in Dynamic Military Networks Using Software Defined Networking

    OpenAIRE

    Skappel, Hans Fredrik

    2016-01-01

    This thesis looks at how Software Defined Networking (SDN) can be used to provide traffic engineering and to police traffic in an Operational Military Network (OMN). SDN is a concept where the control plane is separated from the forwarding plane, and the control plane is capable of controlling forwarding plane elements located on multiple network nodes using the OpenFlow protocol. Specifically, we have discussed the problems in OMNs, and possible SDN approaches to mitigate the challenges. Bas...

  6. Software defined network inference with evolutionary optimal observation matrices

    OpenAIRE

    Malboubi, M; Gong, Y; Yang, Z; Wang, X; Chuah, CN; Sharma, P

    2017-01-01

    © 2017 Elsevier B.V. A key requirement for network management is the accurate and reliable monitoring of relevant network characteristics. In today's large-scale networks, this is a challenging task due to the scarcity of network measurement resources and the hard constraints that this imposes. This paper proposes a new framework, called SNIPER, which leverages the flexibility provided by Software-Defined Networking (SDN) to design the optimal observation or measurement matrix that can lead t...

  7. Defining Marketing Strategies For Vihreä Tekno Finland

    OpenAIRE

    Manzari, Mohammad

    2016-01-01

    The main objective of this thesis is to define marketing strategies for Vihreä Tekno, a company in Vantaa, Finland. The company runs several businesses such as providing IT services, website designing, business/loyalty cards, professional logo design, PC repairs and installations, mobile application development, translation services, cleaning services, advertising and distribution services, billing/invoicing systems and so forth. In this thesis, the author analyzed the company’s current s...

  8. Factors Defining Field Germination of Oilseed Radish Seeds

    Directory of Open Access Journals (Sweden)

    N.V. Dorofeev

    2013-08-01

    Full Text Available Influence of temperature, depth of crops and granulometric of soil structure on germination speed, laboratory and field germination of oilseed radish seeds were studied. It was established that the period of seed-germination is defined both by temperature and granulometric structure of soil. The highest field germination was marked on sandy loam at depth of crops' seeds at 3 cm and 20°С.

  9. 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.

  10. Skew category algebras associated with partially defined dynamical systems

    DEFF Research Database (Denmark)

    Lundström, Patrik; Öinert, Per Johan

    2012-01-01

    We introduce partially defined dynamical systems defined on a topological space. To each such system we associate a functor s from a category G to Topop and show that it defines what we call a skew category algebra A ⋊σ G. We study the connection between topological freeness of s and, on the one...... hand, ideal properties of A ⋊σ G and, on the other hand, maximal commutativity of A in A ⋊σ G. In particular, we show that if G is a groupoid and for each e ∈ ob(G) the group of all morphisms e → e is countable and the topological space s(e) is Tychonoff and Baire. Then the following assertions...... are equivalent: (i) s is topologically free; (ii) A has the ideal intersection property, i.e. if I is a nonzero ideal of A ⋊σ G, then I ∩ A ≠ {0}; (iii) the ring A is a maximal abelian complex subalgebra of A ⋊σ G. Thereby, we generalize a result by Svensson, Silvestrov and de Jeu from the additive group...

  11. Defining Disability: Understandings of and Attitudes Towards Ableism and Disability

    Directory of Open Access Journals (Sweden)

    Carli Friedman

    2017-03-01

    Full Text Available Disabled people, amidst political and social gains, continue to experience discrimination in multiple areas. Understanding how such discrimination, named here as ableism, operates is important and may require studying perspectives of people who do not claim a disability identity.  Ableism may be expressed in a number of ways, and examining how a particular group, in this case siblings of disabled people, understand and value disability may contribute to overall understandings about how ableism works. Thus, the purpose of this study is to explore relationships between siblings of disabled people's broad societal understandings of disability and their attitudes towards it. In order to tease out this relationship further we have also examined factors that impact how people define disability. Using both social psychological and sociological approaches, we have contextualized individual attitudes as providing additional new information about social meanings of disability, and set this study's results against the larger backdrops of debates over meanings of disability within Disability Studies. In our research, participants revealed complex understandings of disability, but most often defined disability as preventing or slowing action, as an atypical function, a lack of independence, and as a socially constructed obstacle. Participants' unconscious (implicit disability attitudes significantly related to their understandings of disability as lacking independence, impairment, and/or in relation to the norm, and their conscious (explicit disability attitudes. Moreover, longer employment in a disability-related industry was correlated with defining disability as a general difference, rather than as slowing or limiting of tasks.

  12. An approach to define semantics for BPM systems interoperability

    Science.gov (United States)

    Rico, Mariela; Caliusco, María Laura; Chiotti, Omar; Rosa Galli, María

    2015-04-01

    This article proposes defining semantics for Business Process Management systems interoperability through the ontology of Electronic Business Documents (EBD) used to interchange the information required to perform cross-organizational processes. The semantic model generated allows aligning enterprise's business processes to support cross-organizational processes by matching the business ontology of each business partner with the EBD ontology. The result is a flexible software architecture that allows dynamically defining cross-organizational business processes by reusing the EBD ontology. For developing the semantic model, a method is presented, which is based on a strategy for discovering entity features whose interpretation depends on the context, and representing them for enriching the ontology. The proposed method complements ontology learning techniques that can not infer semantic features not represented in data sources. In order to improve the representation of these entity features, the method proposes using widely accepted ontologies, for representing time entities and relations, physical quantities, measurement units, official country names, and currencies and funds, among others. When the ontologies reuse is not possible, the method proposes identifying whether that feature is simple or complex, and defines a strategy to be followed. An empirical validation of the approach has been performed through a case study.

  13. Protocol independent transmission method in software defined optical network

    Science.gov (United States)

    Liu, Yuze; Li, Hui; Hou, Yanfang; Qiu, Yajun; Ji, Yuefeng

    2016-10-01

    With the development of big data and cloud computing technology, the traditional software-defined network is facing new challenges (e.i., ubiquitous accessibility, higher bandwidth, more flexible management and greater security). Using a proprietary protocol or encoding format is a way to improve information security. However, the flow, which carried by proprietary protocol or code, cannot go through the traditional IP network. In addition, ultra- high-definition video transmission service once again become a hot spot. Traditionally, in the IP network, the Serial Digital Interface (SDI) signal must be compressed. This approach offers additional advantages but also bring some disadvantages such as signal degradation and high latency. To some extent, HD-SDI can also be regard as a proprietary protocol, which need transparent transmission such as optical channel. However, traditional optical networks cannot support flexible traffics . In response to aforementioned challenges for future network, one immediate solution would be to use NFV technology to abstract the network infrastructure and provide an all-optical switching topology graph for the SDN control plane. This paper proposes a new service-based software defined optical network architecture, including an infrastructure layer, a virtualization layer, a service abstract layer and an application layer. We then dwell on the corresponding service providing method in order to implement the protocol-independent transport. Finally, we experimentally evaluate that proposed service providing method can be applied to transmit the HD-SDI signal in the software-defined optical network.

  14. Defining Peer-to-Peer Accountability From the Nurse's Perspective.

    Science.gov (United States)

    Lockett, Jacqueline Jansen; Barkley, Leslie; Stichler, Jaynelle; Palomo, Jeanne; Kik, Bozena; Walker, Christopher; Donnelly, Janet; Willon, Judy; Sanborn, Julie; O'Byrne, Noeleen

    2015-11-01

    The aim of this study was to define and create a conceptual model for peer-to-peer accountability (P to PA). Many organizations cite the importance of peer accountability (PA) as essential in ensuring patient safety. Professionalism in nursing requires self-regulation of practice and PA. Although discussed in the literature, P to PA is not conceptually defined. A grounded theory study design with constant comparative data collection and analysis was used to explore nurses' definitions of P to PA and their perceptions of motivators and barriers to engaging in P to PA. Transcripts of digital recordings of all interviews were analyzed using line-by-line coding until identified themes emerged. P to PA was defined as the act of speaking up when one observes a peer not practicing to acceptable standards. A conceptual model illustrates the antecedents, attributes, and consequences of P to PA. P to PA is the professional responsibility of every nurse and healthcare provider and is essential for safe patient care. The conceptual definition facilitates actualization of P to PA in practice.

  15. Contour junctions defined by dynamic image deformations enhance perceptual transparency.

    Science.gov (United States)

    Kawabe, Takahiro; Nishida, Shin'ya

    2017-11-01

    The majority of work on the perception of transparency has focused on static images with luminance-defined contour junctions, but recent work has shown that dynamic image sequences with dynamic image deformations also provide information about transparency. The present study demonstrates that when part of a static image is dynamically deformed, contour junctions at which deforming and nondeforming contours are connected facilitate the deformation-based perception of a transparent layer. We found that the impression of a transparent layer was stronger when a dynamically deforming area was adjacent to static nondeforming areas than when presented alone. When contour junctions were not formed at the dynamic-static boundaries, however, the impression of a transparent layer was not facilitated by the presence of static surrounding areas. The effect of the deformation-defined junctions was attenuated when the spatial pattern of luminance contrast at the junctions was inconsistent with the perceived transparency related to luminance contrast, while the effect did not change when the spatial luminance pattern was consistent with it. In addition, the results showed that contour completions across the junctions were required for the perception of a transparent layer. These results indicate that deformation-defined junctions that involve contour completion between deforming and nondeforming regions enhance the perception of a transparent layer, and that the deformation-based perceptual transparency can be promoted by the simultaneous presence of appropriately configured luminance and contrast-other features that can also by themselves produce the sensation of perceiving transparency.

  16. Defining and understanding healthy lifestyles choices for adolescents.

    Science.gov (United States)

    He, Ka; Kramer, Ellen; Houser, Robert F; Chomitz, Virginia R; Hacker, Karen A

    2004-07-01

    To: (a) establish criteria for defining positive health behaviors and lifestyle; and (b) identify characteristics of adolescents who practice a healthy lifestyle. Responses from a 1998 survey via questionnaire, of 1487 students, from a public high school, Cambridge, Massachusetts, were used to assess correlates of healthy lifestyle choices. Strict and broad assessments of healthy behaviors were defined for students: use of alcohol, tobacco, and illegal drugs; sexual behavior; attempted suicide. Whereas the "strict" criteria included only those adolescents who did not practice any of the behaviors in question, the broad criteria reflected experimentation and moderate risk-taking. The prevalence of positive behaviors was assessed by demographic and student characteristics. In addition, logistic regression models were created to predict determinants of teenagers' healthy lifestyles using both strict and broad definitions. Using strict criteria of healthy lifestyle, significant predictors were being female, born outside the United States, higher academic performance, and fewer stressful life events. Using a broad definition of a healthy lifestyle, significant predictors were being non-Caucasian, in the lower grade levels at the school, higher academic performance, and fewer stressful life events. In both models, peers' approval of risky behaviors negatively influenced teens' lifestyles, whereas parents' disapproval of risky behaviors was a positive influence. These results reinforce the importance of school, peer, and parent support of positive behaviors. It is important for public health workers and families to understand and define healthy lifestyles choices for adolescents.

  17. Defining and detecting malaria epidemics in south-east Iran

    Directory of Open Access Journals (Sweden)

    McKelvie William R

    2012-03-01

    Full Text Available Abstract Background A lack of consensus on how to define malaria epidemics has impeded the evaluation of early detection systems. This study aimed to develop local definitions of malaria epidemics in a known malarious area of Iran, and to use that definition to evaluate the validity of several epidemic alert thresholds. Methods Epidemic definition variables generated from surveillance data were plotted against weekly malaria counts to assess which most accurately labelled aberrations. Various alert thresholds were then generated from weekly counts or log counts. Finally, the best epidemic definition was used to calculate and compare sensitivities, specificities, detection delays, and areas under ROC curves of the alert thresholds. Results The best epidemic definition used a minimum duration of four weeks and week-specific and overall smoothed geometric means plus 1.0 standard deviation. It defined 13 epidemics. A modified C-SUM alert of untransformed weekly counts using a threshold of mean + 0.25 SD had the highest combined sensitivity and specificity. Untransformed C-SUM alerts also had the highest area under the ROC curve. Conclusions Defining local malaria epidemics using objective criteria facilitated the evaluation of alert thresholds. This approach needs further study to refine epidemic definitions and prospectively evaluate epidemic alerts.

  18. Defining and detecting malaria epidemics in south-east Iran.

    Science.gov (United States)

    McKelvie, William R; Haghdoost, Ali Akbar; Raeisi, Ahmad

    2012-03-23

    A lack of consensus on how to define malaria epidemics has impeded the evaluation of early detection systems. This study aimed to develop local definitions of malaria epidemics in a known malarious area of Iran, and to use that definition to evaluate the validity of several epidemic alert thresholds. Epidemic definition variables generated from surveillance data were plotted against weekly malaria counts to assess which most accurately labelled aberrations. Various alert thresholds were then generated from weekly counts or log counts. Finally, the best epidemic definition was used to calculate and compare sensitivities, specificities, detection delays, and areas under ROC curves of the alert thresholds. The best epidemic definition used a minimum duration of four weeks and week-specific and overall smoothed geometric means plus 1.0 standard deviation. It defined 13 epidemics. A modified C-SUM alert of untransformed weekly counts using a threshold of mean+0.25 SD had the highest combined sensitivity and specificity. Untransformed C-SUM alerts also had the highest area under the ROC curve. Defining local malaria epidemics using objective criteria facilitated the evaluation of alert thresholds. This approach needs further study to refine epidemic definitions and prospectively evaluate epidemic alerts.

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

    Science.gov (United States)

    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 the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion

    Directory of Open Access Journals (Sweden)

    Sandra Capellera-Garcia

    2016-06-01

    Full Text Available Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs. We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.

  1. Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.

    Science.gov (United States)

    Atherly, Todd; Mosher, Curtis; Wang, Chong; Hostetter, Jesse; Proctor, Alexandra; Brand, Meghan W; Phillips, Gregory J; Wannemuehler, Michael; Jergens, Albert E

    2016-11-01

    Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines and to correlate microbiota changes to histopathologic lesions. The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks were investigated by fluorescence in situ hybridization targeting the 16S ribosomal RNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Helicobacter bilis-colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P attachment, or by invasion, and this interaction is differentially expressed over time.

  2. Configuration-defined control algorithms with the ASDEX Upgrade DCS

    Energy Technology Data Exchange (ETDEWEB)

    Treutterer, Wolfgang, E-mail: Wolfgang.Treutterer@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany); Cole, Richard [Unlimited Computer Systems, Seeshaupter Str. 15, 82393 Iffeldorf Germany (Germany); Gräter, Alexander [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany); Lüddecke, Klaus [Unlimited Computer Systems, Seeshaupter Str. 15, 82393 Iffeldorf Germany (Germany); Neu, Gregor; Rapson, Christopher; Raupp, Gerhard; Zehetbauer, Thomas [Max-Planck-Institut für Plasmaphysik, Boltzmannstr. 2, 85748 Garching (Germany)

    2016-11-15

    Highlights: • Control algorithm built from combination of pre-fabricated standard function blocks. • Seamless integration in multi-threaded computation context. • Block composition defined by configuration data, only. - Abstract: The ASDEX Upgrade Discharge Control System (DCS) is a distributed real-time control system executing complex control and monitoring tasks. Up to now, DCS control algorithms have been implemented by coding dedicated application processes with the C++ programming language. Algorithm changes required code modification, compilation and commissioning which only experienced programmers could perform. This was a significant constraint of flexibility for both control system operation and design. The new approach extends DCS with the capability of configuration-defined control algorithms. These are composed of chains of small, configurable standard function blocks providing general purpose functions like algebraic operations, filters, feedback controllers, output limiters and decision logic. In a later phase a graphical editor could help to compose and modify such configuration in a Simulink-like fashion. Building algorithms from standard functions can result in a high number of elements. In order to achieve a similar performance as with C++ coding, it is essential to avoid administrative bottlenecks by design. As a consequence, DCS executes a function block chain in the context of a single real-time thread of an application process. No concurrency issues as in a multi-threaded context need to be considered resulting in strongly simplified signal handling and zero performance overhead for inter-block communication. Instead of signal-driven synchronization, a block scheduler derives the execution sequence automatically from the block dependencies as defined in the configuration. All blocks and connecting signals are instantiated dynamically, based on definitions in a configuration file. Algorithms thus are not defined in the code but only in

  3. Evolution of homeobox genes.

    Science.gov (United States)

    Holland, Peter W H

    2013-01-01

    Many homeobox genes encode transcription factors with regulatory roles in animal and plant development. Homeobox genes are found in almost all eukaryotes, and have diversified into 11 gene classes and over 100 gene families in animal evolution, and 10 to 14 gene classes in plants. The largest group in animals is the ANTP class which includes the well-known Hox genes, plus other genes implicated in development including ParaHox (Cdx, Xlox, Gsx), Evx, Dlx, En, NK4, NK3, Msx, and Nanog. Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes. Expression and functional data suggest that NK, Hox, and ParaHox gene clusters acquired distinct roles in patterning the mesoderm, nervous system, and gut. The PRD class is also diverse and includes Pax2/5/8, Pax3/7, Pax4/6, Gsc, Hesx, Otx, Otp, and Pitx genes. PRD genes are not generally arranged in ancient genomic clusters, although the Dux, Obox, and Rhox gene clusters arose in mammalian evolution as did several non-clustered PRD genes. Tandem duplication and genome duplication expanded the number of homeobox genes, possibly contributing to the evolution of developmental complexity, but homeobox gene loss must not be ignored. Evolutionary changes to homeobox gene expression have also been documented, including Hox gene expression patterns shifting in concert with segmental diversification in vertebrates and crustaceans, and deletion of a Pitx1 gene enhancer in pelvic-reduced sticklebacks. WIREs Dev Biol 2013, 2:31-45. doi: 10.1002/wdev.78 For further resources related to this article, please visit the WIREs website. The author declares that he has no conflicts of interest. Copyright © 2012 Wiley Periodicals, Inc.

  4. Gene cluster statistics with gene families.

    Science.gov (United States)

    Raghupathy, Narayanan; Durand, Dannie

    2009-05-01

    Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such "gene clusters" is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data

  5. Carboxylesterase 1 genes

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Madsen, Majbritt Busk

    2018-01-01

    The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2...

  6. Maximizing biomarker discovery by minimizing gene signatures

    Directory of Open Access Journals (Sweden)

    Chang Chang

    2011-12-01

    Full Text Available Abstract Background The use of gene signatures can potentially be of considerable value in the field of clinical diagnosis. However, gene signatures defined with different methods can be quite various even when applied the same disease and the same endpoint. Previous studies have shown that the correct selection of subsets of genes from microarray data is key for the accurate classification of disease phenotypes, and a number of methods have been proposed for the purpose. However, these methods refine the subsets by only considering each single feature, and they do not confirm the association between the genes identified in each gene signature and the phenotype of the disease. We proposed an innovative new method termed Minimize Feature's Size (MFS based on multiple level similarity analyses and association between the genes and disease for breast cancer endpoints by comparing classifier models generated from the second phase of MicroArray Quality Control (MAQC-II, trying to develop effective meta-analysis strategies to transform the MAQC-II signatures into a robust and reliable set of biomarker for clinical applications. Results We analyzed the similarity of the multiple gene signatures in an endpoint and between the two endpoints of breast cancer at probe and gene levels, the results indicate that disease-related genes can be preferably selected as the components of gene signature, and that the gene signatures for the two endpoints could be interchangeable. The minimized signatures were built at probe level by using MFS for each endpoint. By applying the approach, we generated a much smaller set of gene signature with the similar predictive power compared with those gene signatures from MAQC-II. Conclusions Our results indicate that gene signatures of both large and small sizes could perform equally well in clinical applications. Besides, consistency and biological significances can be detected among different gene signatures, reflecting the

  7. Defining the public, defining sociology: hybrid science-public relations and boundary-work in early American sociology.

    Science.gov (United States)

    Evans, Michael S

    2009-01-01

    In this paper, I examine how scientific disciplines define their boundaries by defining the publics with whom they engage. The case study is an episode in the development of early American sociology. In response to the dual challenge of credibility set up by the conflict between religious Baconian science and secular positivist science, key actors engaged in specific strategies of boundary-work to create their desired "sociological public"--a hybrid form of science-public relations that appealed to hostile university scientists while excluding a supportive religious audience from participation in the production of scientific knowledge. Using this case, I offer two specific insights. First I illustrate how, in the pursuit of scientific credibility, actors engage in boundary-work to differentiate audiences, not just practitioners. Such defining of publics is constitutive of scientific disciplines in their formative stage. Second, I demonstrate how audience boundaries can be redefined through the capture of existing boundary objects. Specifically, the removal of informational content in key boundary objects creates durable boundaries that are difficult to overcome.

  8. Molecular characterization of circulating colorectal tumor cells defines genetic signatures for individualized cancer care

    Science.gov (United States)

    Kong, Say Li; Liu, Xingliang; Suhaimi, Nur-Afidah Mohamed; Koh, Kenneth Jia Hao; Hu, Min; Lee, Daniel Yoke San; Cima, Igor; Phyo, Wai Min; Lee, Esther Xing Wei; Tai, Joyce A.; Foong, Yu Miin; Vo, Jess Honganh; Koh, Poh Koon; Zhang, Tong; Ying, Jackie Y.; Lim, Bing; Tan, Min-Han; Hillmer, Axel M.

    2017-01-01

    Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples. We developed an analysis pipeline to minimize false-positive detection of somatic mutations in amplified DNA. In 60% of the CTC-enriched blood samples, we detected primary tumor matching mutations. We found a significant positive correlation between the allele frequencies of somatic mutations detected in CTCs and abnormal CEA serum level. Strikingly, we found driver mutations and amplifications in cancer and druggable genes such as APC, KRAS, TP53, ERBB3, FBXW7 and ERBB2. In addition, we found that CTCs carried mutation signatures that resembled the signatures of their primary tumors. Cumulatively, our study defined genetic signatures and somatic mutation frequency of colorectal CTCs. The identification of druggable mutations in CTCs of preoperative colorectal cancer patients could lead to more timely and focused therapeutic interventions. PMID:28978093

  9. Use of zebrafish and knockdown technology to define proprotein convertase activity.

    Science.gov (United States)

    Chitramuthu, Babykumari P; Bennett, Hugh P J

    2011-01-01

    The Zebrafish (Danio rerio) is a powerful and well-established tool used extensively for the study of early vertebrate development and as a model of human diseases. Zebrafish genes orthologous to their mammalian counterparts generally share conserved biological function. Protein knockdown or overexpression can be effectively achieved by microinjection of morpholino antisense oligonucleotides (MOs) or mRNA, respectively, into developing embryos at the one- to two-cell stage. Correlating gene expression patterns with the characterizing of phenotypes resulting from over- or underexpression can reveal the function of a particular protein. The microinjection technique is simple and results are reproducible. We defined the expression pattern of the proprotein convertase PCSK5 within the lateral line neuromasts and various organs including the liver, gut and otic vesicle by whole-mount in situ hybridization (ISH) and immunofluorescence (IF). MO-mediated knockdown of zebrafish PCSK5 expression generated embryos that display abnormal neuromast deposition within the lateral line system resulting in uncoordinated patterns of swimming.

  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. Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses.

    Science.gov (United States)

    Schunselaar, Laurel M; Quispel-Janssen, Josine M M F; Kim, Yongsoo; Alifrangis, Constantine; Zwart, Wilbert; Baas, Paul; Neefjes, Jacques

    2018-04-01

    Purpose: Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor. Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment. Results: We observed a high concordance between in vitro results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway. Conclusions: Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7); 1761-70. ©2017 AACR See related commentary by John and Chia, p. 1513 . ©2017 American Association for Cancer Research.

  12. How to Tackle the Challenge of siRNA Delivery with Sequence-Defined Oligoamino Amides.

    Science.gov (United States)

    Reinhard, Sören; Wagner, Ernst

    2017-01-01

    RNA interference (RNAi) as a mechanism of gene regulation provides exciting opportunities for medical applications. Synthetic small interfering RNA (siRNA) triggers the knockdown of complementary mRNA sequences in a catalytic fashion and has to be delivered into the cytosol of the targeted cells. The design of adequate carrier systems to overcome multiple extracellular and intracellular roadblocks within the delivery process has utmost importance. Cationic polymers form polyplexes through electrostatic interaction with negatively charged nucleic acids and present a promising class of carriers. Issues of polycations regarding toxicity, heterogeneity, and polydispersity can be overcome by solid-phase-assisted synthesis of sequence-defined cationic oligomers. These medium-sized highly versatile nucleic acid carriers display low cytotoxicity and can be modified and tailored in multiple ways to meet specific requirements of nucleic acid binding, polyplex size, shielding, targeting, and intracellular release of the cargo. In this way, sequence-defined cationic oligomers can mimic the dynamic and bioresponsive behavior of viruses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Interpretation of Spirometry: Selection of Predicted Values and Defining Abnormality.

    Science.gov (United States)

    Chhabra, S K

    2015-01-01

    Spirometry is the most frequently performed investigation to evaluate pulmonary function. It provides clinically useful information on the mechanical properties of the lung and the thoracic cage and aids in taking management-related decisions in a wide spectrum of diseases and disorders. Few measurements in medicine are so dependent on factors related to equipment, operator and the patient. Good spirometry requires quality assured measurements and a systematic approach to interpretation. Standard guidelines on the technical aspects of equipment and their calibration as well as the test procedure have been developed and revised from time-to-time. Strict compliance with standardisation guidelines ensures quality control. Interpretation of spirometry data is based only on two basic measurements--the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) and their ratio, FEV1/FVC. A meaningful and clinically useful interpretation of the measured data requires a systematic approach and consideration of several important issues. Central to interpretation is the understanding of the development and application of prediction equations. Selection of prediction equations that are appropriate for the ethnic origin of the patient is vital to avoid erroneous interpretation. Defining abnormal values is a debatable but critical aspect of spirometry. A statistically valid definition of the lower limits of normal has been advocated as the better method over the more commonly used approach of defining abnormality as a fixed percentage of the predicted value. Spirometry rarely provides a specific diagnosis. Examination of the flow-volume curve and the measured data provides information to define patterns of ventilatory impairment. Spirometry must be interpreted in conjunction with clinical information including results of other investigations.

  14. Defining recovery in chronic fatigue syndrome: a critical review.

    Science.gov (United States)

    Adamowicz, Jenna L; Caikauskaite, Indre; Friedberg, Fred

    2014-11-01

    In chronic fatigue syndrome (CFS), the lack of consensus on how recovery should be defined or interpreted has generated controversy and confusion. The purpose of this paper was to systematically review, compare, and evaluate the definitions of recovery reported in the CFS literature and to make recommendations about the scope of recovery assessments. A search was done using the MEDLINE, PubMed, PsycINFO, CINAHL, and Cochrane databases for peer review papers that contained the search terms "chronic fatigue syndrome" and "recovery," "reversal," "remission," and/or "treatment response." From the 22 extracted studies, recovery was operationally defined by reference with one or more of these domains: (1) pre-morbid functioning; (2) both fatigue and function; (3) fatigue (or related symptoms) alone; (4) function alone; and/or (5) brief global assessment. Almost all of the studies measuring recovery in CFS did so differently. The brief global assessment was the most common outcome measure used to define recovery. Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies. Given that the term "recovery" was often based on limited assessments and less than full restoration of health, other more precise and accurate labels (e.g., clinically significant improvement) may be more appropriate and informative. In keeping with common understandings of the term recovery, we recommend a consistent definition that captures a broad-based return to health with assessments of both fatigue and function as well as the patient's perceptions of his/her recovery status.

  15. Animal models of physiologic markers of male reproduction: genetically defined infertile mice

    Energy Technology Data Exchange (ETDEWEB)

    Chubb, C.

    1987-10-01

    The present report focuses on novel animal models of male infertility: genetically defined mice bearing single-gene mutations that induce infertility. The primary goal of the investigations was to identify the reproductive defects in these mutant mice. The phenotypic effects of the gene mutations were deciphered by comparing the mutant mice to their normal siblings. Initially testicular steroidogenesis and spermatogenesis were investigated. The physiologic markers for testicular steroidogenesis were steroid secretion by testes perifused in vitro, seminal vesicle weight, and Leydig cell histology. Spermatogenesis was evaluated by the enumeration of homogenization-resistant sperm/spermatids in testes and by morphometric analyses of germ cells in the seminiferous epithelium. If testicular function appeared normal, the authors investigated the sexual behavior of the mice. The parameters of male sexual behavior that were quantified included mount patency, mount frequency, intromission latency, thrusts per intromission, ejaculation latency, and ejaculation duration. Females of pairs breeding under normal circumstances were monitored for the presence of vaginal plugs and pregnancies. The patency of the ejaculatory process was determined by quantifying sperm in the female reproductive tract after sexual behavior tests. Sperm function was studied by quantitatively determining sperm motility during videomicroscopic observation. Also, the ability of epididymal sperm to function within the uterine environment was analyzed by determining sperm capacity to initiate pregnancy after artificial insemination. Together, the experimental results permitted the grouping of the gene mutations into three general categories. They propose that the same biological markers used in the reported studies can be implemented in the assessment of the impact that environmental toxins may have on male reproduction.

  16. DEFINING HUMAN MIGRATION – A POLICY MAKERS PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Paul-Panfil IVAN

    2015-06-01

    Full Text Available Migration is a global phenomenon gradually increased in scope, impact and complexity. Practically all countries are simultaneously countries of destination, origin and transit for migrants. Traditionally migration flows are complemented by new changes generated by economic, demographic, political or social conditions, and these trends affect both the size and structure of the migrant population and also economies and societies. Of course this has sparked international interest from various NGOs and by the European Union and the United Nations. This paper aims to present the vision of international organizations concerned with migration and how they define migration and its typologies.

  17. Homogenization of variational inequalities and equations defined by pseudomonotone operators

    International Nuclear Information System (INIS)

    Sandrakov, G V

    2008-01-01

    Results on the convergence of sequences of solutions of non-linear equations and variational inequalities for obstacle problems are proved. The variational inequalities and equations are defined by a non-linear, pseudomonotone operator of the second order with periodic, rapidly oscillating coefficients and by sequences of functions characterizing the obstacles and the boundary conditions. Two-scale and macroscale (homogenized) limiting problems for such variational inequalities and equations are obtained. Results on the relationship between solutions of these limiting problems are established and sufficient conditions for the uniqueness of solutions are presented. Bibliography: 25 titles

  18. How Do We Define Congenital Heart Defects for Scientific Studies?

    DEFF Research Database (Denmark)

    Garne, Ester; Olsen, Morten Smaerup; Johnsen, Søren Paaske

    2012-01-01

    of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population-based data...... practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD....

  19. Topic B. Disposal objectives: are they fair and properly defined

    International Nuclear Information System (INIS)

    McComble, C.

    1994-01-01

    In this work the author was asked to make some connections between the ethical issues that are presently being discussed and the objectives and the principles which have been espoused in the nuclear waste disposal area. He tries to group it under the following set of questions : are the objectives and principles which we espouse properly defined. Are they sufficiently complete. Have we missed any out. Did we make any additional suggestions. Are they fair when we measure them against these ethical principles. Are they too ambitious. Are we going too far in one direction. (O.L.)

  20. Expert knowledge as defined by the X-Ray Ordinance

    International Nuclear Information System (INIS)

    1987-01-01

    The radiation protection officer or any person responsible for radiation safety have to give proof of their expert knowledge in accordance with sections 3, 4 of the X-Ray Ordinance. Proof of expert knowledge has to be furnished within the procedure of appointment (sec. 13, sub-sec. (3) X-Ray Ordinance). The directive defines the scope of the expert knowledge required, and the scope of expert knowledge persons must have, or acquire, who are responsible for radiation protection within the preview of sec. 23, no. 2, 4 and sec. 29, sub-sec. 1, no. 3 of the X-Ray Ordinance. (orig./HP) [de